[Federal Register Volume 74, Number 221 (Wednesday, November 18, 2009)]
[Rules and Regulations]
[Pages 59608-59686]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-27261]
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Part II
Environmental Protection Agency
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40 CFR Part 180
Carbofuran; Order Denying FMC's Objections and Requests for Hearing;
Final Rule
Federal Register / Vol. 74 , No. 221 / Wednesday, November 18, 2009 /
Rules and Regulations
[[Page 59608]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2005-0162; FRL-8797-6]
Carbofuran; Order Denying FMC's Objections and Requests for
Hearing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Order.
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SUMMARY: In this order, EPA denies objections to, and requests for
hearing on, a final rule revoking all pesticide tolerances for
carbofuran under section 408(d) of the Federal Food, Drug, and Cosmetic
Act (FFDCA). The objections and hearing requests were filed on June 30,
2009, by the National Corn Growers Association, National Sunflower
Association, National Potato Council, and FMC Corporation
(``Petitioners'').
DATES: This final order is effective November 18, 2009.
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2005-0162. To access the
electronic docket, go to http://www.regulations.gov, and search for the
docket number. Follow the instructions on the regulations.gov Web site
to view the docket index or access available documents. All documents
in the docket are listed in the docket index available in
regulations.gov. Although listed in the index, some information is not
publicly available, e.g., Confidential Business Information (CBI) or
other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Jude Andreasen, Pesticide Re-
evaluation Division (7508P), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001; telephone number: (703) 308-9342; e-mail
address: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
In this document EPA denies objections and hearing requests by the
National Corn Growers Association, National Sunflower Association,
National Potato Council, and FMC Corporation (``Petitioners'')
concerning EPA's final rule revoking all pesticide tolerances for
carbofuran. This action may also be of interest to agricultural
producers, food manufacturers, or pesticide manufacturers. Potentially
affected entities may include, but are not limited to:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at http://www.regulations.gov, you may access this Federal Register document
electronically through the EPA Internet under the Federal Register
listings at http://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of EPA's tolerance regulations at
40 CFR part 180 through the Government Printing Office's pilot e-CFR
site at http://www.gpoaccess.gov/ecfr.
C. Acronyms
The following is a list of acronyms used in this order:
AChE--Acetylcholinesterase
aPAD--Acute Population Adjusted Dose
BMD--Bench Mark Dose
BMDL--Bench Mark Dose Level
CCA--Comparative Cholinesterase Assay
CNS--Central Nervous System
CRA--Cumulative Risk Assessment
CSFII--Continuing Survey of Food Intakes by Individuals
CWA--Clean Water Act
CWS--Community Water System
DEEM-FCID--Dietary Exposure Evaluation Model-Food Commodity Intake
Database
ECG--Electrocardiogram
EDWC--Estimated Drinking Water Concentration
EPA--Environmental Protection Agency
FACA--Federal Advisory Committee Act
FDA--Food and Drug Administration
FIFRA--Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA--Federal Food, Drug, and Cosmetic Act
FQPA--Food Quality Protection Act of 1996
HSRB--Human Studies Review Board
HUC-8--8-digit hydrologic unit code
IRED--Interim Reregistration Eligibility Decision
LD50--Lethal Dose for 50% of a population
LOAEL--Lowest Observable Adverse Effect Level
NAWQA--National Water Quality Assessment Program
NHEERL--National Health and Environmental Effects Laboratory
NMC CRA--N-Methyl Carbamate Cumulative Risk Assessment
NOAEL--No Observable Adverse Effect Level
NOIC--Notice of Intent to Cancel
NRDC--National Resources Defense Council
OP--Organophosphate
ORD--Office of Research and Development
PAD--Population Adjusted Dose
PCA--Percent Cropped Area
PCT--Percent Crop Treated
PDP--Pesticide Data Program
PND--Post-Natal Day
PNS--Peripheral Nervous System
PoD--Point of Departure
ppb--parts per billion
ppm--parts per million
PRZM-EXAMS--Pesticide Root Zone Model-Exposure Analysis Model System
RBC--red blood cell
RED--Reregistration Eligibility Decision
RfD--Reference Dose
SAP--Scientific Advisory Panel
SDWA--Safe Drinking Water Act
USDA--United States Department of Agriculture
USGS--United States Geological Survey
WARP--Watershed Regression for Pesticides
II. Introduction
A. What Action Is the Agency Taking?
Exposure to the pesticide carbofuran resulting from existing legal
uses is unsafe--unsafe for the general
[[Page 59609]]
population, and particularly unsafe for infants and children. EPA
reached this conclusion in 2006 after an exhaustive multi-year review
of the data on carbofuran as part of its effort to determine whether
carbofuran should be reregistered under the Federal Insecticide,
Fungicide, and Rodenticide Act (``FIFRA''), and whether the tolerances
allowing carbofuran residues on certain foods met the revised safety
standard in section 408 of the FFDCA. This multi-year review included
multiple opportunities for public participation, including no less than
four formal public comment periods. Following EPA review of yet more
carbofuran data submitted by FMC, the carbofuran registrant, and the
review of EPA's science findings by the FIFRA Scientific Advisory Panel
(SAP)--an independent scientific peer review panel--EPA again reached
the same conclusion in its July 31, 2008 proposal to revoke the
carbofuran tolerances (73 FR 44864 (July 31, 2008)). In response to
this proposed revocation, FMC submitted comments challenging many of
EPA's science findings and also requesting the cancellation of the
registration of carbofuran on several crops and the restriction of
where, and the manner in which, carbofuran could be used in the United
States on its remaining registered crop sites. Finding FMC's science
arguments to be flawed and its proposed amendments to the carbofuran
registration to be insufficient, EPA finalized the rule revoking
carbofuran tolerances on May 15, 2009 (74 FR 23046 (May 15, 2009)).
Pursuant to the procedures of the FFDCA, on June 29, 2009
objections to the final revocation rule were filed by the National Corn
Growers Association, National Sunflower Association, National Potato
Council, and FMC Corporation (``Petitioners''). The Petitioners also
requested a hearing on their objections. Coupled with these objections,
FMC filed on the same day yet another series of proposed amendments to
its carbofuran registration. These proposed modifications contained new
application and geographic restrictions as well as an unprecedented
non-governmental scheme for preventing the use of carbofuran in any one
area of the country above a small percentage of that area's
agricultural acreage. The Petitioners relied on these proposed
carbofuran registration amendments as central to, and inextricably
intertwined with, their objection to EPA's prior determination in the
final rule that carbofuran tolerances are unsafe. Specific challenges
raised by the Petitioners involved EPA's decision on the appropriate
level of the additional safety factor to protect infants and children,
EPA's estimate of carbofuran levels in drinking water, EPA's
consideration of the time needed to recover from exposure to
carbofuran, and EPA's refusal to consider a human toxicity study
conducted with carbofuran.
Today's order denies all of the Petitioners' objections and
requests for hearing. A principal flaw in the Petitioners' objections
is that they have objected to EPA's determination in the final rule on
the safety of carbofuran based on the FIFRA registration amendments
that FMC filed with EPA 45 days after the safety determination was
made. As such, the Petitioners' objections are irrelevant, and thus
immaterial, to the determination EPA made in the final rule. FMC has
the statutory right under FIFRA to request amendment of its carbofuran
registration. What Petitioners may not do is prolong the FFDCA
tolerance revocation process by challenging EPA's safety determination
based on proposed FIFRA registration changes not before EPA at the time
of its final revocation decision.
It should be noted that EPA's decision on the carbofuran tolerances
is not a determination on FMC's proposed registration amendments. FMC
may continue to pursue these amendments and also the re-establishment
of carbofuran tolerances in light of the amendments. Further, FMC may
seek administrative review, and potentially an administrative hearing,
with regard to any adverse decision issued by EPA on its proposed
amendments. But that process must be played out in the future, a future
in which any decision about the safety of carbofuran is made prior to
the re-introduction of carbofuran residues in food and water, rather
than concurrent with the continued exposure of infants and children to
levels of carbofuran residues that EPA has found to be unsafe.
Despite the fact that a central aspect of the Petitioners'
objections is based on a flawed conception of the objection process
(i.e., the notion that the objection process presents the opportunity
for a complete reformulation of the matter in dispute, rather than a
chance for a review of the accuracy of EPA's earlier determination),
EPA has undertaken a comprehensive analysis of the merits of each of
the Petitioners' objections and hearing requests. That analysis shows,
as is exhaustively set out in Unit VI, that none of the Petitioners'
requests for hearing meets the regulatory standard for granting a
hearing and none of the Petitioners' objections has merit. There are
numerous reasons for these conclusions, but two related themes running
throughout EPA's analysis are the Petitioners' failure to timely raise
issues or submit supporting documents during the public comment process
on the proposed rule and the Petitioners' failure to object to how EPA,
in the final rule, resolved the issues the Petitioners did raise in the
comment process. EPA considers issues untimely raised to be waived--as
EPA clearly warned at the proposal stage--and finds recycled comments
on the proposed rule to be irrelevant to the detailed determinations
made in the final rule. The rulemaking phase of the revocation process
has a purpose, and parties treat it lightly at their peril. Finally,
EPA notes that an additional problem with the Petitioners' objections
is that once the newly proposed registration amendments are stripped
from the objections, it is not at all clear that any remaining issues,
even if concluded in the Petitioners' favor, would result in lowering
carbofuran's estimated risks--which EPA has estimated as far exceeding
the safety standard--to an acceptable level. For all of these reasons,
the Petitioners' objections and hearing requests are denied.
B. What Is the Agency's Authority for Taking This Action?
EPA is taking this action pursuant to the authority in FFDCA
section 408(g)(2)(C), which requires the Agency to issue a final order
resolving the objections to its final rule, issued pursuant to
408(b)(1)(b), 408(b)(2)(A), and 408(e)(1)(A). 21 U.S.C. 346a(b)(1)(b),
(b)(2)(A), (e)(1)(A), (g)(2)(C).)
III. Statutory and Regulatory Background
In this Unit, EPA provides background on the relevant statutes and
regulations governing the Petitioners' objections and requests for
hearing as well as on pertinent Agency policies and practices.
A. FFDCA/FIFRA and Applicable Regulations
1. In general. EPA establishes maximum residue limits, or
``tolerances,'' for pesticide residues in food under section 408 of the
FFDCA (21 U.S.C. 346a). Without such a tolerance or an exemption from
the requirement of a tolerance, a food containing a pesticide residue
is ``adulterated'' under section 402 of the FFDCA and may not be
legally moved in interstate commerce (21 U.S.C. 331,
[[Page 59610]]
342). Monitoring and enforcement of pesticide tolerances are carried
out by the U.S. Food and Drug Administration (``FDA'') and the U.S.
Department of Agriculture (``USDA''). Section 408 was substantially
rewritten by the Food Quality Protection Act of 1996 (``FQPA''), which
added the provisions discussed below establishing a detailed safety
standard for pesticides, additional protections for infants and
children, and the process for establishing or revoking tolerances (Pub.
L. 104-170, 110 Stat. 1489 (1996)).
EPA also regulates pesticides under the Federal Insecticide,
Fungicide, and Rodenticide Act (``FIFRA'') (7 U.S.C. 136 et seq.).
While the FFDCA authorizes the establishment of legal limits for
pesticide residues in food, FIFRA requires the approval of pesticides
prior to their sale and distribution (7 U.S.C. 136a(a)), and
establishes a registration regime for regulating the use of pesticides.
FIFRA regulates pesticide use in conjunction with its registration
scheme by requiring EPA review and approval of pesticide labels and
specifying that use of a pesticide inconsistent with its label is a
violation of federal law (7 U.S.C. 136j(a)(2)(G)). In the FQPA,
Congress integrated action under the two statutes by requiring that the
safety standard under the FFDCA be used as a criterion in FIFRA
registration actions as to pesticide uses that result in dietary risk
from residues in or on food (7 U.S.C. 136(bb)), and directing that EPA
coordinate, to the extent practicable, revocations of tolerances with
pesticide cancellations under FIFRA. (21 U.S.C. 346a(l)(1)).
2. Safety standard for pesticide tolerances. Section
408(b)(2)(A)(i) of the FFDCA requires EPA to modify or revoke a
tolerance if EPA determines that the tolerance is not ``safe'' (21
U.S.C. 346a(b)(2)(A)(ii)). Section 408(b)(2)(A)(ii) of the FFDCA
defines ``safe'' to mean that ``there is a reasonable certainty that no
harm will result from aggregate exposure to the pesticide chemical
residue, including all anticipated dietary exposures and all other
exposures for which there is reliable information.'' This includes
exposure through drinking water and in residential settings, but does
not include occupational exposure. Section 408(b)(2)(D) directs EPA, in
making a safety determination, to:
Consider, among other relevant factors--* * *
(vi) Available information concerning the aggregate exposure levels
of consumers (and major identifiable subgroups of consumers) to the
pesticide chemical residue and to other related substances, including
dietary exposure under the tolerance and all other tolerances in effect
for the pesticide chemical residue, and exposure from other non-
occupational sources;
EPA must also consider, in evaluating the safety of tolerances,
``safety factors which * * * are generally recognized as appropriate
for the use of animal experimentation data.'' (21 U.S.C.
346a(b)(2)(D)(ix).)
Risks to infants and children are given special consideration.
Specifically, section 408(b)(2)(C) states that EPA:
Shall assess the risk of the pesticide chemical based on--* * *
(II) Available information concerning the special susceptibility
of infants and children to the pesticide chemical residues,
including neurological differences between infants and children and
adults, and effects of in utero exposure to pesticide chemicals;
(21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)). This provision also
creates a presumptive additional safety factor for the protection of
infants and children. Specifically, it directs that ``[i]n the case of
threshold effects, * * * an additional tenfold margin of safety for the
pesticide chemical residue and other sources of exposure shall be
applied for infants and children to take into account potential pre-
and post-natal toxicity and completeness of the data with respect to
exposure and toxicity to infants and children'' (21 U.S.C.
346a(b)(2)(C)). EPA is permitted to ``use a different margin of safety
for the pesticide chemical residue only if, on the basis of reliable
data, such margin will be safe for infants and children'' (Id.). The
additional safety margin for infants and children is referred to
throughout this order as the ``children's safety factor.''
3. Procedures for establishing, amending, or revoking tolerances.
Tolerances are revoked by rulemaking under the unique procedural
framework set forth in the FFDCA. Section 408(e) of the FFDCA, 21
U.S.C. 346a(e), authorizes EPA to modify or revoke tolerances on its
own initiative.
In issuing a regulation on its own initiative, EPA must first
publish a notice of proposed rulemaking, and must generally provide at
least 60 days to allow the public to comment on the proposed
regulation. After considering comments submitted during this comment
period, EPA issues a final rule.
Once EPA issues a final rule, any person may file objections with
EPA and, if desired, request an evidentiary hearing on those objections
(21 U.S.C. 346a(g)(2)). Objections must specify ``with particularity
the provisions of the regulation * * * deemed objectionable and stating
reasonable grounds therefore'' (21 U.S.C. 346a(g)(2)(A); 40 CFR
178.25(a)). Objections and hearing requests must be filed within 60
days (Id.). The statute provides that EPA shall ``hold a public
evidentiary hearing if and to the extent the Administrator determines
that such a public hearing is necessary to receive factual evidence
relevant to material issues of fact raised by the objections'' (21
U.S.C. 346a(g)(2)(B)). EPA regulations make clear that hearings will
only be granted where it is shown that there is ``a genuine and
substantial issue of fact;'' the requestor has identified evidence
``which, if established, will resolve one or more of such issues in
favor of the requestor,'' and the issue is ``determinative'' with
regard to the relief requested (40 CFR 178.32(b)). After consideration
of any objections, EPA must issue a final order stating the action
taken in response to each objection, including a determination as to
whether any hearing is appropriate (21 U.S.C. 346a(g)(2)(C)). The final
order also establishes any revisions to the final regulation EPA deems
to be warranted based on the objections. Id. EPA's final order on the
objections is subject to judicial review in the Court of Appeals,
within 60 days of the publication of the order (21 U.S.C. 346a(h)(1)).
4. Tolerance reassessment and FIFRA reregistration. EPA revoked the
carbfuran tolerances to implement the Agency's findings made during the
reregistration and tolerance reassessment processes.
The FQPA required that EPA reassess the safety of all pesticide
tolerances existing at the time of its enactment. (21 U.S.C. 346a(q)).
EPA was given 10 years to reassess the approximately 10,000 tolerances
in existence in 1996. In this reassessment, EPA was required to review
existing pesticide tolerances under the new ``reasonable certainty that
no harm will result'' standard set forth in section 408(b)(2)(A)(i).
(21 U.S.C. 346a(b)(2)(A)(i)). This reassessment was substantially
completed by the August 3, 2006 deadline. Tolerance reassessment was
generally handled in conjunction with a similar program involving
reregistration of pesticides under FIFRA. (7 U.S.C. 136a-1).
Reassessment and reregistration decisions were generally combined in a
document labeled a Reregistration Eligibility Decision (RED).
[[Page 59611]]
B. EPA's Human Research Rule
EPA decisions regarding the use of human studies in pesticide
regulatory decisions are governed by the Protection for Subjects in
Human Research final rule (``Human Research rule''), which
significantly strengthened and expanded protections for subjects of
human research (71 FR 6138 (February 6, 2006)). The framework of the
Human Research rule rests on the basic principle that EPA will not, in
its actions, rely on data derived from unethical research. The rule
divides studies involving intentional dosing of human subjects into two
groups: ``new'' studies--those initiated after April 7, 2006 (the
effective date of the rule)--and ``old'' studies--those initiated
before April 7, 2006. The Human Research Rule forbids EPA from relying
on data from any ``new'' study, unless EPA has adequate information to
determine that the research was conducted in substantial compliance
with the ethical requirements contained therein (40 CFR 26.1705). These
ethical rules are derived primarily from the ``Common Rule,'' (40 CFR
part 26), a rule setting ethical parameters for studies conducted or
supported by the federal government. In addition to requiring informed
consent and protection of the safety of the subjects, among other
things, the rule specifies that ``[r]isks to subjects [must be]
reasonable in relation to * * * the importance of the knowledge that
may reasonably be expected to result [from the study].'' (40 CFR
26.1111(a)(2)). In other words, a study would be judged unethical if it
did not have scientific value outweighing any risks to the test
subjects.
As to ``old'' studies, the Human Research Rule forbids EPA from
relying on such data if there is clear and convincing evidence that the
conduct of the research was fundamentally unethical or significantly
deficient with respect to the ethical standards prevailing at the time
the research was conducted (40 CFR 26.1704). EPA has indicated that in
evaluating ``the ethical standards prevailing at the time the research
was conducted'' it will consider the Nuremburg Code, various editions
of the Declaration of Helsinki, the Belmont Report, and the Common
Rule, as among the standards that may be applicable to any particular
study (71 FR at 6161). Further, reflecting the concern that
scientifically invalid data are ``always unethical,'' (71 FR at 6160),
the rule limits the human research that can be relied upon by EPA to
``scientifically valid and relevant data'' (40 CFR 26.1701).
Whether the data are ``new'' or ``old,'' the Human Research rule
forbids EPA from relying on data from any study involving intentional
exposure of pregnant women, fetuses, or children subject to a very
limited exception (40 CFR 26.1703, 1706).
To aid EPA in making scientific and ethical determinations under
the Human Research rule, the rule established an independent Human
Studies Review Board (HSRB) to review both proposals for new research
(new studies) and reports of completed human research (old studies) on
which EPA proposes to rely (40 CFR 26.1603). The rule directs that the
HSRB shall be comprised of non-EPA employees ``who have expertise in
fields appropriate for the scientific and ethical review of human
research, including research ethics, biostatistics, and human
toxicology'' (40 CFR 26.1603(a)). If EPA decides to rely on the results
from ``old'' research conducted to identify or measure a toxic effect,
EPA must submit the results of its assessment to the HSRB for
evaluation of the ethical and scientific merit of the research (40 CFR
26.1602(b)(2)).
EPA has established the HSRB as a federal advisory committee under
the Federal Advisory Committee Act (FACA) to take advantage of ``the
benefits of the transparency and opportunities for public
participation'' that accompany a FACA committee (71 FR at 6156). The
HSRB, as appointed by EPA, contains approximately 16 distinguished
experts in the fields of bioethics, biostatistics, human health risk
assessment and human toxicology, primarily from academia (Ref. 10).
IV. EPA's Approach to Dietary Risk Assessment
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. A short summary is provided
below to aid the reader. For further discussion of the regulatory
requirements of section 408 of the FFDCA and a complete description of
the risk assessment process, see http://www.epa.gov/fedrgstr/EPA-PEST/1999/January/Day-04/p34736.htm.
To assess the risk of a pesticide tolerance, EPA combines
information on pesticide toxicity with information regarding the route,
magnitude, and duration of exposure to the pesticide. The risk
assessment process involves four distinct steps: (1) Identification of
the toxicological hazards posed by a pesticide; (2) determination of
the exposure ``level of concern'' for humans; (3) estimation of human
exposure; and (4) characterization of human risk based on comparison of
human exposure to the level of concern.
A. Hazard Identification and Selection of Toxicological Endpoint
1. In General. Any risk assessment begins with an evaluation of a
chemical's inherent properties, and whether those properties have the
potential to cause adverse effects (i.e., hazard identification). EPA
then evaluates the hazards to determine the most sensitive and
appropriate adverse effect of concern, based on factors such as the
effect's relevance to humans and the likely routes of exposure.
Once a pesticide's potential hazards are identified, EPA determines
a toxicological level of concern for evaluating the risk posed by human
exposure to the pesticide. In this step of the risk assessment process,
EPA essentially evaluates the levels of exposure to the pesticide at
which effects might occur. An important aspect of this determination is
assessing the relationship between exposure (dose) and response (often
referred to as the dose-response analysis). In evaluating a chemical's
dietary risks EPA uses a reference dose (RfD) approach, which involves
a number of considerations including:
A `point of departure' (PoD)--the value from a dose-
response curve that is at the low end of the observable data and that
is the dose that serves as the `starting point' in extrapolating a risk
to the human population;
An uncertainty factor to address the potential for a
difference in toxic response between humans and animals used in
toxicity tests (i.e., interspecies extrapolation);
An uncertainty factor to address the potential for
differences in sensitivity in the toxic response across the human
population (i.e., intraspecies variability); and
The need for an additional safety factor to protect
infants and children, as specified in FFDCA section 408(b)(2)(C).
EPA uses the chosen PoD to calculate a safe dose or RfD. The RfD is
calculated by dividing the chosen PoD by all applicable safety or
uncertainty factors. Typically in EPA risk assessments, a combination
of safety or uncertainty factors providing at least a hundredfold
(100X) margin of safety is used: 10X to account for interspecies
extrapolation and 10X to account for intraspecies variability. Further,
as required by FFDCA section 408(b)(2)(C), in evaluating the dietary
risks for pesticide chemicals, an additional safety factor of 10X is
presumptively applied to protect infants and children, unless reliable
data support selection of a different
[[Page 59612]]
factor. In implementing FFDCA section 408, EPA also calculates a
variant of the RfD referred to as a Population Adjusted Dose (PAD). A
PAD is the RfD divided by any portion of the children's safety factor
that does not correspond to one of the traditional additional
uncertainty/safety factors used in general Agency risk assessment. The
reason for calculating PADs is so that other parts of the Agency, which
are not governed by FFDCA section 408, can, when evaluating the same or
similar substances, easily identify which aspects of a pesticide risk
assessment are a function of the particular statutory commands in FFDCA
section 408. For acute assessments, the risk is expressed as a
percentage of a maximum acceptable dose or the acute PAD (i.e., the
acute dose which EPA has concluded will be ``safe''). As discussed
below in Unit V.C., dietary exposures greater than 100 percent of the
acute PAD are generally cause for concern and would be considered
``unsafe'' within the meaning of FFDCA section 408(b)(2)(B). Throughout
this document general references to EPA's calculated safe dose are
denoted as an acute PAD, or aPAD, because the relevant point of
departure for carbofuran is based on an acute risk endpoint.
2. Acetylcholinesterase Inhibition. Carbofuran is a member of the
class of pesticides called N-methyl carbamates (NMCs). The primary
toxic effect caused by NMCs, including carbofuran, is neurotoxicity
resulting from inhibition of the enzyme acetylcholinesterase (AChE).
The toxicity profile of these pesticides is characterized by rapid time
to onset of effects followed by rapid recovery (minutes to hours).
Consistent with its mechanism of action, toxicity data on AChE
inhibition from laboratory rats provide the basis for deriving the PoD
for carbofuran.
AChE inhibition is a disruption of the normal process in the body
by which the nervous system chemically communicates with muscles and
glands. Communication between nerve cells and a target cell (i.e.,
another nerve cell, a muscle fiber, or a gland) is facilitated by the
chemical, acetylcholine. When a nerve cell is stimulated it releases
acetylcholine into the synapse (or space) between the nerve cell and
the target cell. The released acetylcholine binds to receptors in the
target cell, stimulating the target cell in turn. As EPA has explained,
``the end result of the stimulation of cholinergic pathway(s) includes,
for example, the contraction of smooth (e.g., in the gastrointestinal
tract) or skeletal muscle, changes in heart rate or glandular secretion
(e.g., sweat glands) or communication between nerve cells in the brain
or in the autonomic ganglia of the peripheral nervous system.'' (Ref.
78 at 10).
AChE is an enzyme that breaks down acetylcholine and terminates its
stimulating action in the synapse between nerve cells and target cells.
When AChE is inhibited, acetylcholine builds up prolonging the
stimulation of the target cell. This excessive stimulation potentially
results in a broad range of adverse effects on many bodily functions
including muscle cramping or paralysis, excessive glandular secretions,
or effects on learning, memory, or other behavioral parameters.
Depending on the degree of inhibition these effects can be serious,
even fatal.
EPA's cholinesterase inhibition policy statement explains EPA's
approach to evaluating the risks posed by AChE-inhibiting pesticides
such as carbofuran (Ref. 78 at 10). The policy focuses on three types
of effects associated with AChE-inhibiting pesticides that may be
assessed in animal and human toxicological studies: (1) Physiological
and behavioral/functional effects; (2) AChE inhibition in the central
and peripheral nervous system; and (3) AChE inhibition in red blood
cells and blood plasma. The policy discusses how such data should be
integrated in deriving an acceptable dose (RfD/PAD) for a AChE-
inhibiting pesticide.
After clinical signs or symptoms, AChE inhibition in the nervous
system provides the next most important endpoint for evaluating AChE-
inhibiting pesticides. Although AChE inhibition in the nervous system
is not itself regarded as a direct adverse effect, it is ``generally
accepted as a key component of the mechanism of toxicity leading to
adverse cholinergic effects'' (Id. at 25). As such, the policy states
that it should be treated as ``direct evidence of potential adverse
effects'' and ``data showing this response provide valuable information
in assessing potential hazards posed by antiAChE pesticides'' (Id.).
Unfortunately, useful data measuring AChE inhibition in the peripheral
nervous system tissues has only been relatively rarely captured by
standard toxicology testing, particularly for the NMC compounds. For
central nervous system effects, however, more recent neurotoxicity
studies ``have sought to characterize the time course of inhibition in
* * * [the] brain, including brain regions, after acute and 90-day
exposures'' (Id. at 27).
AChE inhibition in the blood is one step further removed from the
direct harmful consequences of AChE-inhibiting pesticides. According to
the policy, inhibition of blood AChEs ``is not an adverse effect, but
may indicate a potential for adverse effects on the nervous system''
(Id. at 28). The policy states that ``[a]s a matter of science policy,
blood AChE data are considered appropriate surrogate measures of
potential effects on peripheral nervous system AChE activity in
animals, for central nervous system (``CNS'') AChE activity in animals
when CNS data are lacking and for both peripheral and central nervous
system AChE in humans'' (Id. at 29). The policy notes that ``there is
often a direct relationship between a greater magnitude of exposure [to
a AChE-inhibiting pesticide] and an increase in incidence and severity
of clinical signs and symptoms as well as blood AChE inhibition'' (Id.
at 30). Thus, the policy regards blood AChE data as ``appropriate
endpoints for derivation of reference doses or concentrations when
considered in a weight-of-the-evidence analysis of the entire database
* * *'' (Id. at 29). Between AChE inhibition measured in red blood cell
(``RBC'') or blood plasma, the policy states a preference for reliance
on RBC AChE measurements because plasma is composed of a mixture of
acetylcholinesterase and butyrylcholinesterase, and inhibition of the
latter is less clearly tied to inhibition of acetylcholinesterase in
the nervous system (Id. at 29, 32).
EPA has relied on a benchmark dose (BMD) approach for deriving the
PoD from the available rat toxicity studies. A BMD is a point estimate
along a dose-response curve that corresponds to a specific response
level. For example, a BMD10 represents a 10% change from the
background; 10% is often used as a typical value for the response of
concern (Ref. 76). Generically, the direction of change from background
can be an increase or a decrease depending on the biological parameter
and the chemical of interest. In the case of carbofuran, inhibition of
AChE is the toxic effect of concern. Following exposure to carbofuran,
the normal biological activity of the AChE enzyme is decreased (i.e.,
the enzyme is inhibited). Thus, when evaluating BMDs for carbofuran,
the Agency is interested in a decrease in AChE activity compared to
normal activity levels, which are also termed ``background'' levels.
Measurements of ``background'' AChE activity levels are usually
obtained from animals in experimental studies that are not treated with
the pesticide of interest (i.e., ``negative control'' animals).
In addition to the BMD, a confidence limit was also calculated.
Confidence limits express the uncertainty in a BMD that may be due to
sampling and/or
[[Page 59613]]
experimental error. The lower confidence limit on the dose used as the
BMD is termed the BMDL, which the Agency uses as the PoD. Use of the
BMDL for deriving the PoD rewards better experimental design and
procedures that provide more precise estimates of the BMD, resulting in
tighter confidence intervals. Use of the BMDL also helps ensure with
high confidence (e.g., 95% confidence) that the selected percentage of
AChE inhibition is not exceeded. From the PoD, EPA calculates the RfD
and aPAD. Specific to carbofuran and the other NMCs, EPA the FIFRA SAP
has reviewed and supported the statistical methods used to derive the
BMD and BMDLs on multiple occasions (Refs. 34, 35, 36).
In the Agency's BMD analysis for carbofuran, EPA used a response
level of 10% brain AChE inhibition; this value represents the estimated
dose where AChE is inhibited by 10%, compared to untreated animals. For
the last several years EPA has used the 10% value to regulate AChE
inhibiting pesticides, including organophosphorous pesticides (OPs) and
NMCs. For a variety of toxicological and statistical reasons, EPA chose
10% brain AChE inhibition as the response level for use in BMD
calculations. EPA analyses have demonstrated that 10% is a level that
can be reliably measured in the majority of rat toxicity studies; is
generally at or near the limit of sensitivity for discerning a
statistically significant decrease in AChE activity across the brain
compartment; and is a response level close to the background (Refs. 34,
35).
B. Estimating Human Dietary Exposure Levels
Pursuant to section 408(b) of the FFDCA, EPA has evaluated
carbofuran's dietary risks based on ``aggregate exposure'' to
carbofuran. By ``aggregate exposure,'' EPA is referring to exposure to
carbofuran by multiple pathways of exposure. EPA uses available data
and standard analytical methods, together with assumptions designed to
be protective of public health, to produce separate estimates of
exposure for a highly exposed subgroup of the general population, for
each potential pathway and route of exposure. For acute risks, EPA then
calculates potential aggregate exposure and risk by using probabalistic
\1\ techniques to combine distributions of potential exposures in the
population for each route or pathway. For dietary analyses, the
relevant sources of potential exposure to carbofuran are from the
ingestion of residues in food and drinking water. The Agency uses a
combination of monitoring data and predictive models to evaluate
environmental exposure of humans to carbofuran.
---------------------------------------------------------------------------
\1\ Probabilistic analysis is used to predict the frequency with
which variations of a given event will occur. By taking into account
the actual distribution of possible consumption and pesticide
residue values, probabilistic analysis for pesticide exposure
assessments ``provides more accurate information on the range and
probability of possible exposure and their associated risk values''
(Ref. 77). In capsule, a probabilistic pesticide exposure analysis
constructs a distribution of potential exposures based on data on
consumption patterns and residue levels and provides a ranking of
the probability that each potential exposure will occur. People
consume differing amounts of the same foods, including none at all,
and a food will contain differing amounts of a pesticide residue,
including none at all.
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1. Exposure from Food. The level of human exposure to pesticide
residues in food is a function of both the pesticide residues in food
and the amount of food consumed. Data on the residues of carbofuran in
foods are available from a variety of sources. One of the primary
sources of data comes from federally-conducted surveys, including the
Pesticide Data Program (PDP) conducted by the USDA. Further, market
basket surveys, which are typically performed by registrants, can
provide additional residue data. These data generally provide a
characterization of pesticide residues in or on foods consumed by the
U.S. population that closely approximates real world exposures because
they are sampled closer to the point of consumption in the chain of
commerce than field trial data, which are generated to establish the
maximum level of legal residues that could result from maximum
permissible use of the pesticide. In certain circumstances, when EPA
believes the information will provide more accurate exposure estimates,
EPA will rely on field trial data (see below in Unit VI.E.1).
EPA relies on USDA's Continuing Survey of Food Intake by
Individuals (CSFII) for information on food consumption by the US
population as well as 32 subgroups based on age, gender, ethnicity, and
region. The latest CSFII was conducted in 1994-1996 and 1998. The 1998
survey was a special survey required by the FQPA to supplement the
number of children survey participants. DEEM-FCID also contains
``recipes'' that convert foods as consumed (e.g., pizza) back into
their component raw agricultural commodities (e.g., wheat from flour,
or tomatoes from sauce, etc.). This is necessary because residue data
are generally gathered on raw agricultural commodities rather than on
finished ready-to-eat food. Data on residue values for a particular
pesticide and the RfD or PADs for that pesticide are inputs to the
DEEM-FCID computer program to estimate exposure and risk.
The DEEM-FCID computer program estimates exposure by combining data
on human consumption amounts with residue values in food commodities.
DEEM-FCID also compares exposure estimates to appropriate RfD or PAD
values to estimate risk. EPA uses DEEM-FCID to estimate exposure for
the general U.S. population as well as for 32 subgroups based on age,
sex, ethnicity, and region. DEEM-FCID allows EPA to process extensive
volumes of data on human consumption amounts and residue levels in
making risk estimates. Matching consumption and residue data, as well
as managing the thousands of repeated analyses of the consumption
database conducted under probabilistic risk assessment techniques,
requires the use of a computer.
For carbofuran's assessment, EPA used DEEM-FCID to calculate risk
estimates based on a probabilistic distribution. DEEM-FCID combines the
full range of residue values for each food with the full range of data
on individual consumption amounts to create a distribution of exposure
and risk levels. More specifically, DEEM-FCID creates this distribution
by calculating an exposure value for each reported day of consumption
per person (``person/day'') in CSFII, assuming that all foods
potentially bearing the pesticide residue contain such residue at a
value selected randomly from the exposure data sets. The exposure
amounts for the thousands of person/days in the CSFII are then
collected in a frequency distribution. EPA also uses DEEM-FCID to
compute a distribution taking into account both the full range of data
on consumption levels and the full range of data on potential residue
levels in food. Combining consumption and residue levels into a
distribution of potential exposures and risk requires use of
probabilistic techniques.
The probabilistic technique that DEEM-FCID uses to combine
differing levels of consumption and residues involves the following
steps:
(1) Identification of any food(s) that could bear the residue in
question for each person/day in the CSFII;
(2) Calculation of an exposure level for each of the thousands of
person/days in the CSFII database, based on the foods identified in
Step 1 by randomly selecting residue values for the foods from
the residue database;
(3) Repetition of Step 2 one thousand times for each
person/day; and
[[Page 59614]]
(4) Collection of all of the hundreds of thousands of potential
exposures estimated in Steps 2 and 3 in a frequency
distribution.
The resulting probabilistic assessment presents a range of
exposure/risk estimates.
2. Exposure from water. EPA may use field monitoring data and/or
simulation water exposure models to generate pesticide concentration
estimates in drinking water. Monitoring and modeling are both important
tools for estimating pesticide concentrations in water and can provide
different types of information. Monitoring data can provide estimates
of pesticide concentrations in water that are representative of the
specific agricultural or residential pesticide practices in specific
locations, under the environmental conditions associated with a
sampling design (i.e., the locations of sampling, the times of the year
samples were taken, and the frequency by which samples were collected).
Although monitoring data can provide a direct measure of the
concentration of a pesticide in water, it does not always provide a
reliable basis for estimating spatial and temporal variability in
exposures because sampling may not occur in areas with the highest
pesticide use, and/or when the pesticides are being used and/or at an
appropriate sampling frequency to detect high concentrations of a
pesticide that occur over the period of a day to several days.
Because of the limitations in most monitoring studies, EPA's
standard approach is to use simulation water exposure models as the
primary means to estimate pesticide exposure levels in drinking water.
Modeling is a useful tool for characterizing vulnerable sites, and can
be used to estimate peak pesticide water concentrations from
infrequent, large rain events. EPA's computer models use detailed
information on soil properties, crop characteristics, and weather
patterns to estimate water concentrations in vulnerable locations where
the pesticide could be used according to its label (69 FR 30042, 30058-
30065 (May 26, 2004)). These models calculate estimated water
concentrations of pesticides using laboratory data that describe how
fast the pesticide breaks down to other chemicals and how it moves in
the environment at these vulnerable locations. The modeling provides an
estimate of pesticide concentrations in ground and surface water.
Depending on the modeling algorithm (e.g., surface water modeling
scenarios), daily concentrations can be estimated continuously over
long periods of time, and for places that are of most interest for any
particular pesticide.
EPA relies on models it has developed for estimating pesticide
concentrations in both surface water and ground water. Typically EPA
uses a two-tiered approach to modeling pesticide concentrations in
surface and ground water. If the first tier model suggests that
pesticide levels in water may be unacceptably high, a more refined
model is used as a second tier assessment. The second tier model for
surface water is actually a combination of two models: The Pesticide
Root Zone Model (PRZM) and the Exposure Analysis Model System (EXAMS).
The second tier model for ground water uses PRZM alone.
A detailed description of the models routinely used for exposure
assessment is available from the EPA OPP Water Models Web site: http://www.epa.gov/oppefed1/models/water/index.htm. These models provide a
means for EPA to estimate daily pesticide concentrations in surface
water sources of drinking water (a reservoir) using local soil, site,
hydrology, and weather characteristics along with pesticide application
and agricultural management practices, and pesticide environmental fate
and transport properties. Consistent with the recommendations of the
FIFRA SAP, EPA also considers regional percent cropped area factors
(PCA) which take into account the potential extent of cropped areas
that could be treated with pesticides in a particular area. The PRZM
and EXAMS models used by EPA were developed by EPA's Office of Research
and Development (ORD), and are used by many international pesticide
regulatory agencies to estimate pesticide exposure in surface water.
EPA's use of the percent cropped area factors and the Index Reservoir
scenario was reviewed and approved by the FIFRA SAP in 1999 and 1998,
respectively (Refs. 30, 31).
In modeling potential surface water concentrations, EPA attempts to
model areas of the country that are vulnerable to surface water
contamination rather than simply model ``typical'' concentrations
occurring across the nation. Consequently, EPA models exposures
occurring in small, highly agricultural watersheds in different growing
areas throughout the country, over a 30-year period. The scenarios are
designed to capture residue levels in drinking water from reservoirs
with small watersheds with a large percentage of land use in
agricultural production. EPA's models take into account that pesticide
residues in water fluctuate daily, seasonally, and yearly as a result
of the timing of pesticide applications, the vulnerability of the water
supply to pesticide loading through runoff, spray drift and/or
leaching, and changes in the weather. Concentrations are also affected
by the method of application, the location and characteristics of the
sites where a pesticide is used, the climate, and the type and degree
of pest pressure.
EPA uses the output of daily concentration values from tier two
modeling as an input to DEEM-FCID, which combines water concentrations
with drinking water consumption information in the daily diet to
generate a distribution of exposures from consumption of drinking water
contaminated with pesticides. These results are then used to calculate
a probabilistic assessment of the aggregate human exposure and risk
from residues in food and drinking water.
3. Aggregate Exposure Analyses. Using probabilistic analyses, EPA
combines the national food exposures with the exposures derived for
individual region and crop-specific drinking water scenarios to derive
estimates of aggregate exposure. Although food is distributed
nationally, and exposures to pesticide residues are therefore not
expected to vary substantially throughout the country, drinking water
is locally derived and consumed and there can be significant variations
in pesticide levels in local watersheds due to geographic, climatic,
and other factors. To be protective of all population subgroups, EPA
uses modeled estimates from vulnerable watersheds in calculating
aggregate exposure.
EPA's standard acute dietary exposure assessment calculates total
dietary exposure over a 24-hour period; that is consumption over 24
hours is summed and no account is taken of the fact that eating and
drinking occasions may spread out exposures over a day. This total
daily exposure generally provides reasonable estimates of the risks
from acute dietary exposures, given the nature of most chemical
endpoints. Due to the rapid recovery associated with carbofuran
toxicity (AChE inhibition), 24-hour exposure periods may or may not be
appropriate. To the extent that a day's eating or drinking occasions
leading to high total daily exposure might be found close together in
time, or to occur from a single eating event, minimal AChE recovery
would occur between eating occasions (i.e., exposure events). In that
case, the ``24-hour sum'' approach, which sums eating events over a 24-
hour period, would provide reasonable estimates of risk from food
[[Page 59615]]
and drinking water. Conversely, to the extent that eating occasions
leading to high total daily exposures are widely separated in time
(within one day) such that substantial AChE recovery occurs between
eating occasions, then the estimated risks under any 24-hour sum
approach may be overstated. In that case, a more sophisticated
approach--one that accounts for intra-day eating and drinking patterns
and the recovery of AChE between exposure events--may be more
appropriate. This approach is referred to as the ``Eating Occasions
Analysis'' and it takes into account the fact that the toxicological
effect of a first dose may be reduced or tempered prior to a second (or
subsequent) dose.
Thus, rather than treating a full day's exposure as a one-time
``bolus'' dose, as is typically done in the Agency's assessments, the
Eating Occasion analysis uses the actual time of eating or drinking
occasion, and amounts consumed as reported by individuals to the USDA
CSFII. The actual CSFII-recorded time of each eating event is used to
``separate out'' the exposures due to each eating occasion; in doing
so, this ``separation'' allows the Agency to distinguish between each
intake event and account for the fact that at least some partial
recovery of AChE inhibition attributable to the first (earlier)
exposure occurs before the second exposure event. For chemicals for
which the toxic effect is rapidly reversible, the time between two (or
more) exposure events permits partial to full recovery from the toxic
effect from the first exposure and it is this ``partial recovery'' that
is specifically accounted for by the Eating Occasion Analysis. More
specifically, an estimated ``persisting dose'' from the first exposure
event is added to the second exposure event to account for the partial
recovery of AChE inhibition that occurs over the time between the first
and second exposures. The `persisting dose' terminology, and this
general approach were originally suggested by the FIFRA SAP in the
context of assessing AChE inhibition from cumulative exposures to OP
pesticides (Ref. 33).
C. Selection of Acute Dietary Exposure Level of Concern
Because probabilistic assessments generally are based on a
realistic range of residue values to which the population may be
exposed, EPA's starting point for estimating exposure and risk for such
aggregate assessments is the 99.9th percentile of the population under
evaluation, which represents one person out of every 1000 persons. When
using a probabilistic method of estimating acute dietary exposure, EPA
typically assumes that, when the 99.9th percentile of acute exposure is
equal to or less than the aPAD, the level of concern for acute risk has
not been exceeded. By contrast, where the analysis indicates that
estimated exposure at the 99.9th percentile exceeds the aPAD, EPA would
generally conduct one or more sensitivity analyses to determine the
extent to which the estimated exposures at the high-end percentiles may
be affected by unusually high food consumption or residue values. To
the extent that one or a few values seem to ``drive'' the exposure
estimates at the high end of exposure, EPA would consider whether these
values are reasonable and should be used as the primary basis for
regulatory decision making (Ref. 77).
V. Carbofuran Background and Regulatory History
A. Tolerance Reassessment and Pesticide Reregistration
In July 2006, EPA completed a refined acute probabilistic dietary
risk assessment for carbofuran as part of the tolerance reassessment
program under section 408(q) of the FFDCA and pesticide reregistration
under section 4 of FIFRA. The assessment was conducted using Dietary
Exposure Evaluation Model-Food Commodity Intake Database (DEEM-
FCIDTM, Version 200-2.02), which incorporates consumption
data from the United States Department of Agriculture's (USDA's)
Nationwide Continuing Surveys of Food Intake by Individuals (CSFII),
1994-1996 and 1998, as well as carbofuran monitoring data from USDA's
Pesticide Data Program \2\ (PDP), estimated percent crop treated
information, and processing/cooking factors, where applicable. The
assessment was conducted applying an additional 500-fold safety factor
that included a 5X children's safety factor, pursuant to section
408(b)(2)(C). That refined assessment showed acute dietary risks from
carbofuran residues in food significantly above EPA's level of concern
(Ref. 14). Based in part on the results of that assessment, EPA
concluded that carbofuran failed to meet the revised safety standard in
FFDCA section 408(b) and the standard for FIFRA reregistration.\3\
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\2\ USDA's Pesticide Data Program monitors for pesticides in
certain foods at the distribution points just before release to
supermarkets and grocery stores.
\3\ Although not relevant to this proceeding, in addition to
determining that use of carbofuran resulted in unacceptable dietary
risks, EPA concluded that use of carbofuran did not meet the
standard for FIFRA registration based on unacceptable occupational
and ecological risks.
---------------------------------------------------------------------------
The tolerance reassessment and FIFRA reregistration process for
carbofuran contained numerous opportunities for public participation.
These included public comment periods on the preliminary ecological
risk assessment (June-August 2005), the preliminary human health risk
assessment (September-November 2005), the revised combined risk
assessment (March-May 2006), and the interim Registration Eligibility
Document (RED) (August-November 2006). EPA received over 200 comments
(plus a letter campaign supporting carbofuran with 2,896 signatories)
to the 2006 RED. FMC submitted extensive comments throughout the
process (including, but not limited to, a comment of 62 pages plus 13
attachments totaling over 900 pages on August 23, 2005, a letter with
20 attachments on November 11, 2005, 46 pages of comments on January
26, 2006, 78 pages of comments on February 17, 2006, a 15-page letter
with 8 attachments on May 22, 2006, over 200 pages on May 24, 2006, and
other submissions. Following issuance of the RED in August 2006, FMC
stated that they would be submitting new data to refute EPA's
ecological and human health risk concerns, as well as EPA's benefits
assessments. Twenty-three submissions with studies and analyses were
submitted in 2007, all of which EPA reviewed. FMC submitted 175 pages
of comments to the proposed tolerance revocations jointly with the NPC,
NCGA, NCC, and NSA on 9/29/09. The Agency has also met numerous times
with FMC, growers, and other stakeholders regarding carbofuran.
One particular aspect of the risk assessment process that involved
substantial public participation opportunities was EPA's review of the
human toxicology studies performed with carbofuran. In making a
determination on whether these studies met the standards of the Human
Research rule, EPA, as required, sought the advice of the HSRB. The
HSRB review process includes the opportunity for the public both to
submit written comments and to make an oral presentation to the HSRB.
FMC gave both written and oral comments at the HSRB meeting, which was
held May 2-4, 2006. FMC also submitted written comments on the final
HSRB report on the meeting.
[[Page 59616]]
B. Draft Notice of Intent to Cancel Carbofuran Registrations
In January 2008, EPA published a draft Notice of Intent to Cancel
(NOIC) all carbofuran registrations, based in part on carbofuran's
dietary risks. As mandated by FIFRA, EPA solicited comments from the
FIFRA Scientific Advisory Panel (SAP) on its draft NOIC.\4\ As part of
that process, EPA presented its dietary risk assessment of carbofuran
to the FIFRA SAP, and requested comment on key issues in the risk
assessment: The Agency's approach to selecting the point of departure
and the children's safety factor. FMC and the remaining Petitioners
participated in this meeting, making substantial presentations to the
SAP. As described in the proposal, the Agency believes that the Panel's
responses unambiguously support the Agency's approach with regard to
carbofuran's hazard identification and hazard characterization (73 FR
44875 (July 31, 2008)). In addition, EPA believes that, on balance, the
application of a 4X children's safety factor is consistent with the
SAP's advice. Additional detail on the SAP's advice and EPA's responses
can be found at Ref. 83.
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\4\ The draft NOIC was based on all of carbofuran's combined
risks--dietary, occupational, and ecological. Because some non-food
use registrations remain, EPA anticipates issuing the NOIC
subsequent to undertaking the activities required to revoke the
carbofuran tolerances to cancel these remaining uses.
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C. Proposed Revocation of Carbofuran Tolerances
Having considered the comments from the SAP, EPA initiated the
process to revoke all carbofuran tolerances, publishing a proposed
revocation on July 31, 2008 (73 FR 44,864 (July 31, 2008) (FRL-8378-
8)). EPA proposed to revoke all of the existing tolerances for residues
of carbofuran on the grounds that aggregate exposure from all uses of
carbofuran fails to meet the FFDCA section 408 safety standard (Id).
Based on the contribution from food alone, EPA calculated dietary
exposures to carbofuran exceed EPA's level of concern for all of the
more sensitive subpopulations of infants and children. At the 99.9th
percentile, aggregate carbofuran dietary exposure from food and
drinking water from contaminated ground water was estimated to range
from 1100% of the aPAD for adults, to greater than 10,000% of the aPAD
for infants, the population subgroup with the highest estimated dietary
exposure (Ref. 12). Similarly, aggregate dietary exposures from food
and drinking water from surface water, based on contamination from use
on corn in Nebraska, ranged from 340% of the aPAD for adults, to 3,900%
aPAD for infants. EPA also determined that, based on actual residue
levels measured in food in commerce, individual children consuming
typical amounts of a single food item received unsafe levels of
carbofuran. For example, based on the level of residues detected on in
the food supply, a child between 3-5 years, who consumed \1/2\ cup of
cantaloupe, would receive a dose ranging between 180% and 7,200% of the
aPAD. Finally, the proposal discussed a number of sensitivity analyses
the Agency had calculated in order to further characterize the
potential risks to children. Every one of these sensitivity analyses
determined that estimated exposures significantly exceeded EPA's level
of concern for children.
EPA held a 60-day comment period on the proposed revocation rule.
In the proposed rule, EPA made clear that if any person had concerns
with EPA's proposed revocation, those concerns must be raised during
the comment period to be preserved. Specifically, EPA stated:
In addition to submitting comments in response to this proposal,
you may also submit an objection at the time of the final rule. If
you anticipate that you may wish to file objections to the final
rule, you must raise those issues in your comments on this proposal.
EPA will treat as waived, any issue not originally raised in
comments on this proposal. Similarly, if you fail to file an
objection to the final rule within the time period specified, you
will have waived the right to raise any issues resolved in the final
rule. After the specified time, issues resolved in the final rule
cannot be raised again in any subsequent proceedings on this rule.
(73 FR at 44865).
D. Petitioners' Comments on the Proposed Rule
The comment period for the proposed rule closed on September 29,
2008. During the comment period, the Petitioners submitted comments
challenging particular aspects of EPA's risk assessment. For example,
the Petitioners challenged the basis for EPA's 4X children's safety
factor, and the method and assumptions on which EPA relied to estimate
drinking water concentrations. In addition, the registrant, FMC
Corporation, requested that EPA cancel the use on 22 of the crops on
which it was registered, including many of the foods posing the highest
risks to children. FMC also requested that EPA modify its labels to
include a number of additional restrictions intended to mitigate the
risks identified in EPA's risk assessment. For example, use was
prohibited on much of the Eastern US to protect vulnerable sources of
groundwater; use restrictions were imposed in other areas of the
country, preventing use within set distances to prevent runoff into
sources of surface water drinking water supplies.
On November 7, 2008, the Petitioners submitted additional
information as a supplement to their September comments. Specifically,
they submitted carbofuran use data that the Petitioners used in
preparing its surface water assessments. The information consisted of a
spreadsheet that contained all of the data provided to the Water Panel
by FMC, and a document that explained the materials, methods, and
procedures employed by the Panel to utilize this data.
On December 24, 2008, FMC submitted a petition requesting that EPA
stay the effective date of the tolerance revocations, and that EPA
consider additional information, including further risk mitigation
measure that the registrant intended to implement, as well as
additional analyses that the Petitioners' experts were developing.
E. Final Rule Revoking Carbofuran Tolerances
On May 15, 2009, EPA published its final rule, based on a revised
risk assessment that addressed the voluntary cancellations and label
restrictions submitted by the close of the September 29 comment period.
The only food uses that remained registered after the voluntary
cancellations were sunflowers, corn, potatoes, and pumpkins. In
response to the changes made on the labels, EPA revised its risk
assessment to account for the reduced number of crops, the altered
geographic restrictions, and the additional risk mitigation measures
proposed as part of FMC's comments.
Having considered all comments received by the close of the comment
period, and based on its revised analyses, EPA concluded that aggregate
exposures from all remaining uses of carbofuran were still unsafe for
infants and children, and that revocation of the remaining tolerances
was warranted. The final rule explained that, although the recent
cancellation of several registered uses reduced the dietary risks to
children, EPA's analyses still showed that estimated exposures
significantly exceed EPA's level of concern for children. For example,
EPA determined that the estimated risks could be as high as 9,400% of
the aPAD for infants. A detailed description of the risk assessment
supporting the final rule follows.
[[Page 59617]]
1. Toxicity. AChE inhibition in brain and the PNS is the initial
adverse biological event which results from exposure to carbofuran, and
with sufficient levels of inhibition leads to other effects such as
tremors, dizziness, as well as gastrointestinal and cardiovascular
effects, including bradycardia (Ref. 15). Thus, AChE inhibition
provides the most appropriate effect to use in risk extrapolation for
derivation of RfDs and PADs. Protecting against AChE inhibition ensures
that the other adverse effects associated with cholinergic toxicity,
mentioned above, do not occur.
There are three studies available that compare the effects of
carbofuran on eleven-day-old rats (i.e., post-natal day 11 or PND11)
rats with those in young adult rats (herein called comparative AChE
studies) (Refs. 1, 2, 4, and 66). Two of these studies were submitted
by FMC, the registrant, and one was performed by EPA-ORD. An additional
study conducted by EPA-ORD involved PND17 rats (Ref. 63). Although it
is not possible to directly correlate ages of juvenile rats to humans,
PND11 rats are believed to be close in development to newborn humans.
PND17 rats are believed to be closer developmentally to human toddlers
(Refs. 10, 22, and 23). Other studies in adult rats used in the
Agency's analysis included additional data from EPA-ORD (Refs. 54, 62,
and 66).
The studies in juvenile rats show a consistent pattern that
juvenile rats are more sensitive than adult rats to the effects of
carbofuran. These effects include inhibition in AChE in addition to
incidence of clinical signs of neurotoxicity such as tremors. This
pattern has also been observed for other NMC pesticides, which exhibit
the same mechanism of toxicity as carbofuran (Ref. 81). It is not
unusual for juvenile rats, or indeed, for infants or young children, to
be more sensitive to chemical exposures as metabolic detoxification
processes in the young are still developing. Because juvenile rats,
called `pups' herein, are more sensitive than adult rats, data from
pups provide the most relevant information for evaluating risk to
infants and young children and are thus used to derive the PoD. In
addition, typically (and this is the case for carbofuran) young
children (ages 0-5 years) tend to be the age groups most exposed to
carbofuran because they tend to ingest larger amounts of food and water
per their body weight than do teenagers or adults. As such, the focus
of EPA's analysis of carbofuran's dietary risk from residues in food
and water is on young children (ages 0 to 5 years). Since these age
groups experience the highest levels of dietary risk, protecting these
groups against the effects of carbofuran will, in turn, also protect
other age groups.
The Agency used a meta-analysis to calculate the BMD10
and BMDL10 for pups and adults; this analysis includes brain
data from studies where either adult or juvenile rats or both were
exposed to a single oral dose of carbofuran. The Agency used a dose-
time-response exponential model where benchmark dose and half-life to
recovery can be estimated together. This model and the statistical
approach to deriving the BMD10 s, BMDL10 s, and
half-life to recovery have been reviewed and supported by the FIFRA SAP
(Refs. 34, 35, and 36). The meta-analysis approach offers the advantage
over using single studies by combining information across multiple
studies and thus provides a robust PoD.
For AChE-inhibiting pesticides, EPA generally evaluates the effects
of the pesticide on both brain and RBC AChE. RBC AChE is used as a
surrogate for effects on the PNS because data directly measuring
effects on the PNS are difficult to obtain.
Using quality brain AChE data from the three studies (two FMC, one
EPA-ORD) conducted with PND11 rats, in combination, provides data to
describe both low and high doses. By combining the three studies in
PND11 animals together in a meta-analysis, the entire dose-response
range is covered. The results of the BMD analysis for PND11 pup brain
AChE data provide a BMD10 of 0.04 mg/kg/day and
BMDL10 of 0.03 mg/kg/day--this BMDL10 of 0.03 mg/
kg/day provides the PoD (Ref. 70).
EPA, however, lacked adequate data on carbofuran's effects on RBC
AChE. Two studies required from FMC were rejected as flawed. To account
for the lack of data in the PNS and/or a surrogate (i.e., RBC AChE
inhibition data) in pups at the low end of the response curve, and for
the fact that RBC AChE inhibition appears to be a more sensitive point
of departure compared to brain AChE inhibition, EPA determined that,
consistent with the statutory mandate, some portion of the statutory
default 10X children's safety factor needed to be retained. Because
there are some carbofuran data that characterize the toxicity in
juveniles, EPA concluded that the weight-of-the-evidence supports
reducing the statutory factor of 10X to a value lower than 10X. This
results in a children's safety factor that is less than 10 but more
than 1.
The modified children's safety factor takes into account the
greater sensitivity of the RBC AChE. The preferred approach to
comparing the relative sensitivity of brain and RBC AChE inhibition
would be to compare the BMD10 estimates. However,
BMD10 estimates from the available RBC AChE inhibition data
are not reliable due to lack of data at the low end of the dose
response curve. As an alternative approach, EPA used the ratio of brain
to RBC AChE inhibition at the BMD50, since there are quality
data at or near the 50% response level such that a reliable estimate
can be calculated. EPA estimated the RBC BMD50 to brain
BMD50 potency ratio using EPA's data for RBC (the only
reliable RBC data in PND11 animals for carbofuran) and all available
data in PND11 animals for brain. There is, however, an assumption
associated with using the 50% response level--namely that the magnitude
of difference between RBC and brain AChE inhibition is constant across
dose. In other words, EPA is assuming the RBC and brain AChE dose
response curves are parallel. There are currently no data to test this
assumption for carbofuran.
Comparing RBC BMD50 and brain BMD50 AChE
inhibition, EPA calculated a BMD50 ratio of 4.1X.
Accordingly, EPA concluded that a children's safety factor of 4X would
be protective of infants and children.
Using the BMDL10 of 0.03 mg/kg/day, combined with the
default 10X interspecies and intraspecies factors, along with the 4X
children's safety factor results in an aPAD = 0.000075 mg/kg/day for
infants and children. The aPAD for youths and adults is calculated in
the same manner, but EPA does not apply the 4X children's safety
factor, resulting in an aPAD of 0.0002 mg/kg/day.
2. Acute Exposures from Food. The estimated acute dietary exposure
from carbofuran residues in food alone (i.e., assuming no additional
carbofuran exposure from drinking water), is below EPA's level of
concern for the U.S. Population and all population subgroups. Children
1 to 2 years of age (78% aPAD) were the most highly exposed population
subgroup when food only was included. The major driver of the acute
dietary exposure risk (food only) for Children 1 to 2 years is milk, at
greater than 90% of the exposure.
3. Acute Exposures from Drinking Water. EPA's analyses show that
those individuals-both adults as well as children--who receive their
drinking water from vulnerable sources are exposed to levels that
exceed EPA's level of concern--in some cases by orders of magnitude.
This primarily includes those populations consuming drinking water from
ground water from
[[Page 59618]]
shallow wells in acidic aquifers overlaid with sandy soils that have
had crops treated with carbofuran. It could also include those
populations that obtain their drinking water from reservoirs located in
small agricultural watersheds, prone to runoff, and predominated by
crops that are treated with carbofuran, although there is more
uncertainty associated with these exposure estimates.
a. Ground Water. In EPA's revised assessment, ground water
concentrations were estimated for all remaining crops on carbofuran
labels, and used two new Tier 2 scenarios. Based on a new corn
scenario, representative of potentially vulnerable areas in the upper
Midwest, EPA estimated 1-in-10-year concentrations for ground water
source drinking water of 16 to 1.6 x 10-3 [mu]g/L, for pH
6.5 and 7, respectively. A potato scenario representing use in the
Northwest estimated no measurable concentrations of carbofuran in
ground water. Other remaining uses were modeled using a Tier 1 ground
water model (Screening Concentration in Groundwater) with estimated
peak 90-day concentrations of 48-178 [mu]g/L, depending on application
rate. Well setback prohibitions of 50 feet were proposed on the
September 2008 label for the flowable and granular formulations in
select counties in Kentucky (seven counties), Louisiana (one county),
Minnesota (one county), and Tennessee (one county). Analysis of the
impact of these setbacks for the use on corn indicated that the
setbacks would not reduce concentrations significantly at locations
where exposure to carbofuran in ground water is of concern because at
acid pHs, carbofuran does not degrade sufficiently during the travel
time from the application site to the well to substantially reduce the
concentration.
Exposure estimates for this assessment are drawn primarily from
EPA's modeling. To conduct its modeling, EPA examined readily available
data with respect to ground water and soil pH to evaluate the spatial
variability of pH. Ground water pH values can span a wide range; this
is especially true for shallow ground water systems, where local
conditions can greatly affect the quality and characteristics of the
water (higher or lower pHs compared to average values). The ground
water simulations reflect variability in pH by modeling carbofuran
leaching in four different pH conditions (pH 5.25, 6.5, 7.0, and 8.7),
representing the range in the Wisconsin aquifer system. The upper and
lower bound of pH values that EPA chose for this assessment were
measured values from the aquifer, and the remaining two values were
chosen to reflect common pH values between the measured values. Based
on EPA's assessment, the maximum 1-in-10-year peak carbofuran
concentrations in vulnerable ground water for a single application on
corn in Wisconsin, at a rate of 1 pound per acre were estimated to
range from a low of less than 1 ppb based on a pH of 7 or higher, to a
high of 16 ppb, based on a pH of 6.5.
The results of EPA's revised corn modeling, based on a scenario in
Wisconsin, are consistent with the results of the PGW study developed
by FMC in Maryland in the early 1980s. Using higher use rates than
currently permitted, the peak concentration measured in the PGW study
was 65 ppb; when scaled to current use rates, the estimated peak
concentration was 11 ppb. EPA's modeling is also consistent with a
number of other targeted ground water studies conducted in the 1980s
showing that high concentrations of carbofuran can occur in vulnerable
areas; the results of these studies as well as the PGW study are
summarized in References 13 and 67.
While there have been additional ground water monitoring studies
that included carbofuran as an analyte since that time, there has been
no additional monitoring targeted to carbofuran use in areas where
aquifers are vulnerable. However, data compiled in 2002 by EPA's Office
of Water show that carbofuran was detected in treated drinking water at
a few locations. Based on samples collected from 12,531 ground water
supplies in 16 states, carbofuran was found at one public ground water
system at a concentration of greater than 7 ppb and in two ground water
systems at concentrations greater than 4 ppb (measurements below this
limit were not reported). An infant receiving these concentrations
would receive doses equivalent to 220% of the aPAD or 130% aPAD,
respectively, based on a single 8 ounce serving of water. As this
monitoring was not targeted to carbofuran, the likelihood is low that
these samples capture peak concentrations. Given the lack of targeted
monitoring, EPA has primarily relied on modeling to develop estimates
of carbofuran residues in ground water sources of drinking water.
EPA compiled a distribution of estimated carbofuran concentrations
in water based on these estimates, which was used to generate
probabilistic assessments of the potential exposures from drinking
water derived from vulnerable ground water sources. Based on these
assessments, estimated exposures ranged between 770% aPAD for adults to
9400% aPAD for infants.
b. Surface Water. For the final rule, EPA conducted additional
refined modeling based on the September 2008 label submitted by FMC.
The modeling addressed all of the domestic uses that remain registered,
and included certain refinements to better understand the impacts of
varying pH. EPA also conducted modeling to assess the impact of the
proposed spray drift buffer requirements and other spray drift measures
included on the September label.
EPA estimated carbofuran concentrations resulting from the use on
pumpkins by adjusting the estimated drinking water concentrations
(EDWC) from a previous run simulating melons in Missouri; adjustments
accounted for differences in application rate and row spacing. Two
EDWCs were calculated for pumpkins: One based on a 36-inch row spacing,
representing pumpkins for consumption (77.6 ppb); and a second based on
a 60-inch row spacing, representing decorative pumpkins (46.6 ppb).
EPA had previously evaluated the corn rootworm rescue treatment at
seven representative sites, representing use in states with extensive
carbofuran usage at locations more vulnerable than most in each state
in areas corn is grown. Using measured rainfall values, and assuming
typical rather than maximum use rates, peak concentrations for the corn
rescue treatments simulated for Illinois, Iowa, Indiana, Kansas,
Minnesota, Nebraska, and Texas ranged from 16.6-36.7 ppb (Ref. 47).
Under the revised assessment to account for the September 2008 use
restrictions, concentrations for corn, calculated including the
proposed spray drift buffers in Kansas and Texas, decreased 5.1% and
4.7%, respectively, from simulations with no buffer from the previous
assessment (Ref. 47). In Kansas, the 1-in-10-year peak EDWCs decreased
from 33.5 to 31.8 ppb when a 300-foot buffer was added, and in Texas,
from 29.9 to 28.5 ppb with the addition of a 66-foot buffer.
For the sunflower use, 12 simulations were performed for
sunflowers, 9 in Kansas, and 3 in North Dakota. The North Dakota
scenario was used to represent locations where sunflowers are grown
that are vulnerable to pesticide movement to surface water while the
Kansas scenario represents places that are not particularly vulnerable,
based on the limited rainfall and generally well-drained soils
(hydrologic group B soils) that are found in that area. Estimated 1-in-
10-year concentrations ranged from 11.6 to 32.7
[[Page 59619]]
[mu]g/L. When simulating three applications, one at plant and two
foliar with a 14-day interval between the two foliar applications and a
66-foot buffer, the 1-in-10-year peak EDWC for North Dakota was 22.4
[mu]g/L. In contrast, the same three applications in Kansas with a 14-
day interval between the foliar applications and a 300-foot buffer
produced a 1-in-10-year peak EDWC of 20.5 [mu]g/L. The 1-in-10-year
peak EDWCs, assuming that carbofuran is applied only at plant, were
14.0 and 16.0 [mu]g/L in Kansas and North Dakota respectively. EPA also
evaluated the impact of pH on carbofuran concentrations for sunflowers,
resulting in a 10% decrease in 1-in-10-year peak concentrations
assuming high pH in the reservoir. Spray drift buffers of 66 and 300
feet decreased concentrations 4.7 and 5.1% for corn and 10.0% and 16.0%
for sunflowers, respectively, in comparison to previous labels that had
no spray drift buffer requirements. Additional details on these
assessments can be found at Reference 84.
These predicted carbofuran water concentrations are similar or
lower than the peak concentrations reported in the United States
Geological Survey-National Ambient Water Quality Survey (USGS-NAWQA)
monitoring data. In addition, these data, which represent
concentrations in surface water prior to any treatment by a public
drinking water system, are consistent with the results of the 2002 data
on finished water compiled by EPA's Office of Water. Based on samples
collected from 1,394 surface water source drinking water supplies in 16
states, carbofuran was found at no public drinking water supply systems
at concentrations exceeding maximum contaminant level (MCL) of 40 ppb.
However, carbofuran was found at one surface water public water system
in finished (i.e., post-treatment) water at concentrations greater than
4 ppb (measurements below this limit were not reported). Sampling is
costly and is conducted typically four times a year or less at any
single drinking water facility. The overall likelihood of collecting
samples that capture peak exposure events is, therefore, low. For
chemicals with acute risks of concern, such as carbofuran, higher
concentrations and resulting risk is primarily associated with these
peak events, which are not likely to be captured in monitoring unless
the sampling rate is very high.
There are few surface water field-scale studies targeted to
carbofuran use that could be compared with modeling results. Most of
these studies were conducted in fields that contain tile drains, which
is a common practice throughout midwestern states to increase drainage
in agricultural fields (Ref. 13). Drains are common in the upper
Mississippi river basin (Illinois, Iowa, and the southern part of
Minnesota), and the northern part of the Ohio River Basin (Indiana,
Ohio, and Michigan) (Ref. 58). Although it is not possible to directly
correlate the concentrations found in most of the studies with drinking
water concentrations, these studies confirm that carbofuran use under
such circumstances can contaminate surface water, as tile drains have
been identified as a conduit to transport water and contaminants from
the field to surface waters.
EPA conducted dietary exposure analyses based on the modeling
scenarios for the proposed September 2008 label. Exposures from all
modeled scenarios substantially exceeded EPA's level of concern (Ref.
12). For example, a Kansas sunflower scenario, assuming two foliar
applications at a typical 1 lb active ingredient (a.i.) per acre use
rate, applied at 14-day intervals, estimated a 1-in-10-year peak
carbofuran water concentration of 11.6 ppb. Exposures at the 99.9th
percentile based on this modeled distribution ranged from 160% of the
aPAD for youths 13 to 19 years, to greater than 2,000% of the aPAD for
infants. This scenario is intended to be representative of sites that
are less vulnerable than most on which sunflowers could be grown. By
contrast, exposure estimates from a comparable North Dakota sunflower
scenario, intended to represent more vulnerable sites, estimated a 1-
in-10-year peak concentration of 22.4 ppb. These concentrations would
result in estimated exposures ranging between 450% aPAD for youths 13
to 19 years, to 5,500% aPAD for infants. Similarly, exposures based on
a Washington surface water potato scenario, and using a 3 lb a.i. acre
rate, ranged from 230% of the aPAD for children 6 to 12 years to 890%
of the aPAD for infants, with a 1-in-10-year peak carbofuran
concentration of 7.2 ppb. Although other crop scenarios resulted in
higher exposures, estimates for these two crops are presented here, as
they are major crops on which a large percentage of carbofuran use
occurs. For example, one of EPA's refined exposure analyses is based on
a Nebraska corn rootworm ``rescue treatment'' scenario, and assumes a
single aerial application at a typical rate of 1 lb a.i. per acre. The
full distribution of daily concentrations over a 30-year period was
used in the probabilistic dietary risk assessment. The 1-in-10-year
peak concentration of the distribution of values for the Nebraska corn
rescue treatment was 22.3 ppb. Estimated dietary exposures based on
these concentrations ratned from 340% of the aPAD for adults to 3900%
of the aPAD for infants. More details on these assessments, as well as
the assessments EPA conducted for other crop scenarios, can be found in
References 12, 47, and 67.
4. Aggregate (food and water) Exposures. EPA conducted a number of
probabilistic analyses to combine the national food exposures with the
exposures from the individual region and crop-specific drinking water
scenarios. Although food is distributed nationally, and residue values
are therefore not expected to vary substantially throughout the
country, drinking water is locally derived and consumed and
concentrations of pesticides in source water fluctuate over time and
location for a variety of reasons. Consequently, EPA conducted several
estimates of aggregate dietary risks by combining exposures from food
and drinking water. These estimates showed that, because drinking water
exposures from any of the crops on the label exceed safe levels,
aggregate exposures from food and water are unsafe. Although EPA's
assessments showed that, based on the Idaho potato scenarios, exposures
from ground water from use on potatoes would be safe, surface water
exposures from carbofuran use on potatoes far exceed the safety
standard. More details on the individual aggregate assessments
presented below, as well as the assessments EPA conducted for other
regional and crop scenarios, can be found in References 12 and 13.
The results of aggregate exposures from food and from drinking
water derived from ground water in extremely vulnerable areas (i.e.,
from shallow wells associated with sandy soils and acidic aquifers,
such as are found in Wisconsin), ranged from 780% of the aPAD for
adults, to 9,400% of the aPAD for infants.
The results of aggregate exposure from food and water derived from
one of the least conservative surface water scenarios--Kansas
sunflower, with two foliar applications--ranged from 190% of the aPAD
for adults to 2,100% aPAD for infants. These estimates reflect the
risks only for those people in watersheds with characteristics similar
to that used in the scenario, and assuming that water treatment does
not remove carbofuran. The estimated water concentrations are
comparable to the maximum peak concentrations reported in monitoring
studies that were not designed to detect peak, daily
[[Page 59620]]
concentrations of carbofuran in vulnerable locations.
More details on this assessment, as well as the assessments EPA
conducted for other crop scenarios, can be found in References 12, 47,
and 67. For example, in the proposed rule, EPA presented the results
from aggregate exposures resulting from a Nebraska surface water
scenario based on a Nebraska corn rootworm ``rescue treatment.''
Estimated exposures from that scenario ranged from 330% of the aPAD for
youths 13 to 19 years to 3,900% of the aPAD for infants.
As noted previously, EPA's food and water exposure assessments
typically sum exposures over a 24-hour period, and EPA used this 24-
hour total in developing its acute dietary risk assessment for
carbofuran. Because of the rapid nature of carbofuran toxicity and
recovery, EPA conducted an analysis using information about dietary
exposure, timing of exposure within a day, and half-life of AChE
inhibition from rats to estimate risk to carbofuran at durations less
than 24 hours. Specifically, EPA has evaluated individual eating and
drinking occasions and used the AChE half-life to recovery information
(herein called half-life information) to estimate the residual effects
from carbofuran from previous exposures within the day. The carbofuran
analyses are described in the 2009 aggregate (dietary) memo (Ref. 55).
Using the two FMC time course studies in rat pups, EPA calculated
half-lives for recovery of 186 and 426 minutes (Refs. 24 and 25). The
two values provide an indication that half-lives to recovery can vary
among juvenile rats. By extension, children are expected to vary in
their ability to recover from AChE inhibition where longer recoveries
would be associated with a potentially higher ``persisting dose'' (as
described below).
This analysis had little impact on the exposures from food alone.
However, accounting for drinking water consumption throughout the day
and using the half-life to recovery information, risk is reduced by
approximately 2-3X. Consequently, risk estimates for which food and
drinking water are jointly considered and incorporated (i.e., Food +
Drinking Water) are also reduced considerably--by a factor of two or
more in some cases--compared to baseline. But even though the risk
estimates from aggregate exposure are reduced, they nonetheless still
substantially exceed EPA's level of concern for infants and children.
Using drinking water derived from the surface water from the Idaho
potato surface water scenario, which estimated one of the lowest
exposure distributions, aggregate exposures at the 99.9th percentile
ranged from 328% of the aPAD under the scenario for which infants
rapidly metabolize carbofuran (e.g., 186 minute half-life), to a high
of 473% of the aPAD under the scenario for which infants metabolize
carbofuran more slowly, (e.g., scenarios in which a 426 minute half
life is assumed).
Moreover, even accounting for the estimated decreased risk from
accounting for carbofuran's rapid reversibility, the Agency remains
concerned about the risks from single eating or drinking events, as
illustrated in the following example, based on an actual food
consumption diary from the CSFII survey. A 4-month old male non-nursing
infant weighing 10 kg is reported to have consumed a total of 1,070
milliters (ml) of indirect water over eight different occasions during
the day. The first eating occasion occurred at 6:30 a.m., when this 4
month old consumed 8 fluid ounces of formula prepared from powder. The
FCID food recipes indicate that this particular food item consists of
approximately 87.7% water, and therefore, 8 ounces of formula contains
approximately 214 ml (or grams) of indirect water; with the powder
(various nutrients, dairy, soy, oils, etc.) accounting for the
remaining 12.3%. This infant also reportedly consumed a full 8-ounce
bottle of formula at 12 p.m., 4 p.m., and 8 p.m. that day. The food
diary also indicates that the infant consumed about 1 tablespoon of
water (14.8 ml) added to prepare rice cereal at 10 a.m., about 2 ounces
of water (59.3 ml) added to pear juice at 11 a.m., another \1/2\ tsp of
water (2.5 ml) to prepare more rice cereal at 8:30 p.m.; and finally,
he consumed another 4 ounces of formula (107 ml) at 9:30 p.m.
The infant's total daily water intake (1,070 ml, or approximately
107 ml/kg/day) is not overly conservative, and represents substantially
less than the 90th percentile value from CSFII on a ml water/kg
bodyweight (ml/kg/bw) basis. As noted, carbofuran has been detected in
finished water at concentrations of 4 ppb. For this 10 kg body weight
infant, an 8-ounce bottle of formula prepared from water containing
carbofuran at 4 ppb leads to drinking water exposures of 0.0856
micrograms of active ingredient/kilogram of bodyweight ([micro]g ai/kg
bw), or 114% of the aPAD. Based on the total daily water intake of
1,070 ml/day (no reversibility), total daily exposures from water at 4
ppb concentration would amount to 0.4158 [micro]g ai/kg bw, or 555% of
the aPAD; this is the amount that would be used for this person-day in
the Total Daily Approach.
Peak inhibition occurs following each occasion on which the infant
consumed 8 fluid ounces of formula (6 a.m., 12 p.m., 4 p.m. and 8
p.m.); however, the maximum persisting dose occurs following the 9:30
p.m. eating occasion, based on a 186-minute half-life parameter. This
produces a maximum persisting dose of 0.1457 [micro]g ai/kg bw, or
about 30% of the total daily exposure of 0.4158 [micro]g ai/kg bw
derived above, or expressed as a fraction of the level of concern, the
maximum persisting dose amounts to about 194% of the aPAD (or 30% of
554%). Note that with drinking water concentration at 4 ppb, an infant
consuming one 8 oz bottle of formula--prepared from powder and tap
water containing carbofuran at 4 ppb will obtain exposures of
approximately 114% of aPAD. Since many infants consume the equivalent
of this amount on a single eating occasion, accounting for
reversibility over multiple occasions is not essential to ascertain
that infants quite likely have obtained drinking water exposures to
carbofuran exceeding the level of concern based on drinking water
concentrations found in public drinking water supplies.
In this regard, it is important to note EPA's Eating Occasion
Analyses underestimate exposures to the extent that they do not take
into account carry-over effects from previous days, and because
drinking water pesticide concentrations are randomly picked from the
entire 30-year distribution. As discussed previously, DEEM-FCID
[FN(TM)] is a single day dietary exposure model, and the DEEM-based
Eating Occasion Analysis accounts for reversibility within each
simulated person-day. All of the empirical data regarding time and
amounts consumed (and corresponding exposures based on the
corresponding residues) from the CSFII survey are used, along with the
half-life to assess an equivalent persisting dose that produced the
peak inhibition expected over the course of that day. This is a
reasonable assumption for food alone; since the time between exposure
events across 2 days is relatively high (compared to the half-life)--
most children (>9 months) tend to sleep through the night--and the time
between dinner and breakfast the following morning is long enough it is
reasonable to ``ignore'' persisting effects from the previous day. A
single day exposure model will underestimate the persisting effects
from drinking water exposures (formula) among infants, and newborns in
particular (<3 months), since newborns tend to wake up every 2 to 4
hours to feed. Any carry over
[[Page 59621]]
effects may be important, especially if exposures from the previous day
are relatively high, since the time between the last feeding (formula)
of the day and the first feeding of the subsequent day is short. A
single day model also does not account for the effect of seasonal
variations in drinking water concentrations, which will make this
effect more pronounced during the high use season (i.e., the time of
year when drinking water concentrations are high). Based on these
analyses, the Agency concludes that the current exposure assessment
methods used in the carbofuran dietary assessment provide realistic and
high confidence estimates of risk to carbofuran exposure through food
and water.
F. Response to FMC Comments on the Final Rule
FMC's comments raised a range of issues. Those issues are not
summarized here because FMC basically refilled many of its comments as
objections without modifying them in response to EPA's decision in the
final rule. In addition, FMA submitted a an alternate risk analysis
purporting to show that aggregate carbofuran exposures to children
would be safe. However, FMC failed to provide the data and details of
that assessment to the Agency. They also failed to provide several
critical components that served to support key inputs into that
assessment; and for several of these, EPA was unable to replicate the
claimed results based on the information contained in the comments. In
the absence of such critical components, the Agency was unable to
accept the validity or utility of the analyses, let alone rely on the
results.
Nonetheless, based on the summary descriptions provided in the
registrant's comments, EPA concluded that the risk analyses contained a
critical flaw. The commenters' determination of safety rests on the
presumption that under real world conditions, events will always occur
exactly as hypothesized by the multiple assumptions in their
assessment. For example, the comments assumed, despite all available
evidence to the contrary, that children would not be appreciably more
sensitive to carbofuran's effects than adults. They assumed that
carbofuran's effects will be highly reversible, and that children will
be uniformly sensitive, such that the effects will be adequately
accounted for by the assumption of a 150-minute half-life, despite the
fact that children are not uniformly sensitive. They further assumed
that there would be no carry over effect from the preceding day's
exposures for infants. They assumed that the cancellation of use on
alfalfa would reduce carbofuran residues in milk by over 70%, even
though many cows' diet consists primarily of corn. They assumed that
residues would decrease between 19% and 23% as a result of the buffer
requirements on the September 2008 label, even though the label does
not require the use of all of the recommended ``best management
practices'' (e.g., no requirements regarding swath displacement), and
applicators do not universally use such practices in the absence of any
requirement. They assumed that average ground water pH adequately
characterizes the temporal and spatial heterogeneity common in most
areas, despite the available evidence to the contrary. Finally, they
assumed that the percent of the crop treated in any watershed would
never exceed 5%, despite varying pest pressures, consultant
recommendations, and individual grower decisions. Leaving aside that
EPA believes most, if not all of these assumptions are not supported by
the available evidence described throughout the final rule, the
probability of all these assumptions always simultaneously holding true
under real world conditions is unreasonably low, and certainly does not
approach the degree of certainty necessary for EPA to conclude that
children's exposures will be safe.
Determining whether residues will be safe for U.S. children is not
a theoretical paper exercise; it cannot suffice to hypothesize a unique
set of circumstances that make residues ``fit in the box.'' There must
be a reasonable certainty that under the variability that exists under
real world conditions, exposures will be ``safe.'' EPA's assessments
incorporate a certain degree of conservatism precisely to account for
the fact that assumptions must be made that may not prove accurate.
This consideration is highly relevant for carbofuran, because as
refined as EPA's assessments are, areas of uncertainty remain with
regard to carbofuran's risk potential. For example, a recent
epidemiological study reported that 45% of maternal and cord blood
samples in a cohort of New York City residents of Northern Manhattan
and the South Bronx between 2000 and 2004, contained low, but
measurable residues of carbofuran (Ref. 88). The Agency is currently
unable to account for the source of such sustained exposures at this
frequency.
A further consideration is that the risks of concern are acute
risks to children. For acute risks, the higher values in a
probabilistic risk assessment are often driven by relatively high
values in a few exposures rather than relatively lower values in a
greater number of exposures. This is due to the fact that an acute
assessment looks at a narrow window of exposure where there are
unlikely to be a great variety of consumption sources. Thus, to the
extent that there is a high exposure it will be more likely due to a
high residue value in a single consumption event. Additionally
worrisome in this regard is that carbofuran is a highly potent (i.e.,
has a very steep dose-response curve), acute toxicant, and therefore
any aPAD exceedances are more likely to have greater significance in
terms of the potential likelihood of actual harm. For all of these
reasons, EPA determined that the existing carbofuran tolerances did not
meet the FFDCA safety standard, and should therefore be revoked.
VI. Response to Objections and Requests for Hearing
A. Overview
Petitioners raised several objections that correspond to four basic
categories of issues. The first category of objections and hearing
requests relates to challenges to EPA's selection of the appropriate
children's safety factor. In this category of issues, they raise
primarily two claims: (1) That EPA's scientific basis for retaining a
4X safety factor is flawed, and (2) the statistical calculations
supporting the 4X safety factor are flawed, and based on faulty
assumptions. The second category of issues relate to the manner in
which EPA conducted its assessment of the exposure from carbofuran
through drinking water sources. In this regard, all of their objections
fall within three basic categories of issues: (1) EPA should have
accounted for a more realistic percent of the crop treated (PCT) in its
surface water modeling; (2) EPA's ground water concentration estimates
are not based on the best available data, but on obsolete data and
overly conservative assumptions; and (3) FMC's new label restrictions
and revised terms of registration will ensure that drinking water
concentrations will not exceed 1.1 ppb. The third category of issues
relates to the manner in which EPA conducted its dietary risk
assessment. Under this category, the objections and hearing requests
raise four primary issues: (1) Petitioners challenge the way in which
EPA's risk assessments accounted for individuals to recover from the
effects of carbofuran between exposures; (2) EPA should have relied on
the carbofuran human study and therefore use of the default 10X
interspecies factor is inconsistent with
[[Page 59622]]
the ``best available data; (3) the import tolerances by themselves are
safe and EPA should have retained them even if EPA believed tolerances
associated with the domestic uses were unsafe; and (4) Petitioners
claim that the combined food and water exposures are safe, based on
FMC's drinking water estimates of a 1.1 ppb maximum concentration,
which are guaranteed by new label restrictions submitted as part of
objections. Finally, Petitioners raise one legal objection
unaccompanied by a hearing request. They argue that EPA lacks authority
to limit issues and supporting information that can be raised in
objections and hearing to those raised in earlier comments.
EPA denies each of the Petitioners' objections as well as their
hearing requests. In the first instance, EPA denies Petitioners'
objections and their hearing requests because the objections are
inextricably intertwined with proposed changes to carbofuran's FIFRA
registration that were not submitted until after publication of the
final tolerance revocation rule. Objections to EPA's decision based on
FIFRA registration amendments proposed after EPA's decision are
irrelevant, and thus immaterial, to a challenge to EPA's decision (See
Unit VI.C.). Secondly, an individual analysis of Petitioners'
objections and hearing requests leads to the same conclusion for the
reasons summarized below.
The Petitioners' hearing requests fail to meet the statutory and
regulatory requirements for holding a hearing. In most cases, EPA has
denied the request on the grounds that the objection is irrelevant, and
therefore immaterial, with regard to EPA's final tolerance revocation
regulation. In particular, many claims are immaterial because they
largely restate the claims in their combined comments on EPA's proposed
rule without challenging the substance or even responding to EPA's
explanations for the reasons that EPA declined to adopt the approaches
or otherwise make the revisions suggested by the Petitioners in their
comments. These claims are irrelevant to the determinations reached in
the final rule. In several instances, EPA concluded that Petitioners
evidentiary proffer was inadequate, because the data and information
submitted, even if accurate, would be insufficient to justify the
factual determination urged, or to resolve one or more of the issues in
their favor. Further, in many cases, the evidence submitted constituted
mere allegations and general denials and contentions, which EPA
regulations expressly provide to be insufficient to justify a hearing.
In addition, many of Petitioners' claims do not present genuine and
substantial issues of fact and/or are immaterial to the relief
requested.
On the merits, the majority of Petitioners' objections are denied
for substantially the same reasons given in EPA's final rule and
response to comments. As noted, many of Petitioners' objections are
simply their recycled comments which do not address the conclusions
reached by EPA in the final rule. To the extent a response is even
needed to such a stale claim, it is provided in the final rule and the
response to comments.
The remainder of this Unit is organized in the following manner.
Unit VI.B describes in greater detail the requirements pertaining to
when it is appropriate to grant a hearing request. In Unit VI.C, EPA
generally denies all of Petitioners' objections and hearing requests.
Unit VI.D provides EPA's response to the Petitioners legal objection
that EPA lacks the legal authority to limit the issues and supporting
information that can be raised in an objection and hearing to those
raised in comments on the proposed rule. Units VI. G and I provide
Petitioners' claims regarding EPA's risk assessment. EPA's conclusions
on the hearing requests and objections are summarized in Unit VI.K.
EPA has adopted a 4-part format in Units VI.E through I. for
explaining its ruling on each of the subissues EPA identified in the
objections. First, the Petitioners' claim and any arguments or evidence
tendered to support that claim are described. Second, background
information on the claim is provided including whether and how the
claim was presented in Petitioners' comments and, if it was presented,
EPA's reasons for denying the claim in its final rule and response to
comments. Third, EPA explains its reasons for denying a hearing on that
claim. Finally, EPA explains its reasons for denying the claim on the
merits.
B. The Standard for Granting an Evidentiary Hearing
EPA has established regulations governing objections to tolerance
rulemakings and tolerance petition denials and requests for hearings on
those objections. (40 CFR Part 178; 55 FR 50291 (December 5, 1990)).
Those regulations prescribe both the form and content of hearing
requests and the standard under which EPA is to evaluate requests for
an evidentiary hearing.
As to the form and content of a hearing request, the regulations
specify that a hearing request must include: (1) A statement of the
factual issues on which a hearing is requested and the requestor's
contentions on those issues; (2) a copy of any report, article, or
other written document ``upon which the objector relies to justify an
evidentiary hearing;'' and (3) a summary of any other evidence relied
upon to justify a hearing. (40 CFR 178.27).
The standard for granting a hearing request is set forth in section
178.32. That section provides that a hearing will be granted if EPA
determines that the ``material submitted'' shows all of the following:
(1) There is a genuine and substantial issue of fact for
resolution at a hearing. An evidentiary hearing will not be granted
on issues of policy or law.
(2) There is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one or
more of such issues in favor of the requestor, taking into account
uncontested claims or facts to the contrary. An evidentiary hearing
will not be granted on the basis of mere allegations, denials, or
general descriptions of positions and contentions, nor if the
Administrator concludes that the data and information submitted,
even if accurate, would be insufficient to justify the factual
determination urged.
(3) Resolution of the factual issue(s) in the manner sought by
the person requesting the hearing would be adequate to justify the
action requested. An evidentiary hearing will not be granted on
factual issues that are not determinative with respect to the action
requested. For example, a hearing will not be granted if the
Administrator concludes that the action would be the same even if
the factual issue were resolved in the manner sought.
(40 CFR 178.32(b)).
This provision essentially imposes four requirements upon a hearing
requestor. First, the requestor must show it is raising a question of
fact, not one of law or policy. Hearings are for resolving factual
issues, not for debating law or policy questions. Second, the requestor
must demonstrate that there is a genuine dispute as to the issue of
fact. If the facts are undisputed or the record is clear that no
genuine dispute exists, there is no need for a hearing. Third, the
requestor must show that the disputed factual question is material--
i.e., that it is outcome determinative with regard to the relief
requested in the objections. Finally, the requestor must make a
sufficient evidentiary proffer to demonstrate that there is a
reasonable possibility that the issue could be resolved in favor of the
requestor. Hearings are for the purpose of providing objectors with an
opportunity to present evidence supporting their objections as the
regulation states, hearings will not be granted on the basis of ``mere
allegations, denials, or general
[[Page 59623]]
descriptions of positions or contentions.'' (40 CFR 178.32(b)(2)).
EPA's hearing request requirements are based heavily on FDA
regulations establishing similar requirements for hearing requests
filed under other provisions of the FFDCA (53 FR 41126, 41129 (October
19, 1988)). FDA pioneered the use of summary judgment-type procedures
to limit hearings to disputed material factual issues and thereby
conserve agency resources. FDA's use of such procedures was upheld by
the Supreme Court in 1972, (Weinberger v. Hynson, Westcott & Dunning,
Inc., 412 U.S. 609 (1973)), and, in 1975, FDA promulgated generic
regulations establishing the standard for evaluating hearing requests
(40 FR 22950 (May 27, 1975)). It is these regulations upon which EPA
relied in promulgating its hearing regulations in 1990.
Unlike EPA, FDA has had numerous occasions to apply its regulations
on hearing requests. FDA's summary of the thrust of its regulations,
which has been repeatedly published in the Federal Register in orders
ruling on hearing requests over the last 24 years, is instructive on
the proper interpretation of the regulatory requirements. That summary
states:
A party seeking a hearing is required to meet a threshold burden
of tendering evidence suggesting the need for a hearing.' [] An
allegation that a hearing is necessary to sharpen the issues' or
fully develop the facts' does not meet this test. If a hearing
request fails to identify any evidence that would be the subject of
a hearing, there is no point in holding one.
A hearing request must not only contain evidence, but that
evidence should raise a material issue of fact concerning which a
meaningful hearing might be held. [] FDA need not grant a hearing in
each case where an objection submits additional information or
posits a novel interpretation of existing information. [] Stated
another way, a hearing is justified only if the objections are made
in good faith and if they ``draw in question in a material way the
underpinnings of the regulation at issue.'' Finally, courts have
uniformly recognized that a hearing need not be held to resolve
questions of law or policy
(49 FR 6672, 6673 (February 22, 1984); 72 FR 39557, 39558 (July 19,
2007) (citations omitted)).
EPA has been guided by FDA's application of its regulations in this
proceeding. Congress confirmed EPA's authority to use summary judgment-
type procedures with hearing requests when it amended FFDCA section 408
in 1996. Although the statute had been silent on this issue previously,
the FQPA added language specifying that when a hearing is requested,
EPA ``shall * * * hold a public evidentiary hearing if and to the
extent the Administrator determines that such a public hearing is
necessary to receive factual evidence relevant to material issues of
fact raised by the objections'' (21 U.S.C. 346a(g)(2)(B)). This
language grants EPA broad discretion to determine whether a hearing is
``necessary to receive factual evidence'' to objections (H.R. Rep. No.
104-669, at 49 (1996)).
C. General Denial of Objections and Hearing Requests
Petitioners' objections and hearing requests are denied in their
entirety as irrelevant, and therefore immaterial, to EPA's
determination in the May 15, 2009 final rule that the carbofuran
tolerances were unsafe and could not be sustained under FFDCA section
408. In that final rule, EPA assessed the risks from carbofuran based
on existing uses of carbofuran, as modified by all use restrictions
proposed by FMC. EPA concluded that the carbofuran tolerances
substantially exceeded the FFDCA safety standard, particularly as to
infants and children.
Petitioners' objections and hearing requests as to that final rule
disclose on their face their irrelevance to the conclusions reached in
the May 15, 2009 final rule. As Petitioners summarize their objections
on the first page of their submission:
Petitioners disagree that the carbofuran tolerances are unsafe
and argue that the available scientific data show that there is a
reasonable certainty of no harm to human health from the continued
use of carbofuran for certain specific uses and related tolerances
under the terms for reregistration proposed by Petitioners.
(Objections at 1) (footnote omitted) (emphasis added). As
Petitioners' footnote to this sentence reveals, however, the proposed
terms for FIFRA reregistration referenced by Petitioners include
significant terms submitted to EPA on June 29, 2009, 44 days after
publication of the final rule revoking carbofuran's FFDCA tolerances.
In fact, the body of Petitioners' objections show that FMC's June 29,
2009 proposed FIFRA registration amendments are inextricably
intertwined with the claims made in the objections. Thus, Petitioners
are actually not objecting to the conclusions in EPA's final rule;
rather, they are suggesting that EPA might reach a different result in
a different factual scenario.
Objections, however, must be directed ``with particularity [at] the
provisions of the regulation or order deemed objectionable.'' 21 U.S.C.
346a(g)(2). The key here is that a party must file particularized
objections to--that is, identify some type of error in--a specific
regulatory decision. In no sense, however, can it be claimed that EPA
erred, or that there is something objectionable, in its May 15, 2009
file rule because EPA did not consider a proposed revision to the terms
of the carbofuran registration that had not yet been made. EPA need not
shoot at a moving target, much less a target that is not in existence.
Therefore, Petitioners' objections are irrelevant, and thus immaterial,
to the May 15, 2009 final rule; they are based on hypothetical terms of
carbofuran use not before the Agency as it made its determination in
that final rule.
Moreover, it is not as if Petitioners' proposed terms for
carbofuran use are simple, straightforward use deletions that could be
immediately effectuated. While such a proposal is still irrelevant as a
challenge to a prior EPA determination, such a proposal might lead EPA
to expeditiously modify its action. Rather, Petitioners have proposed
an unprecedented scheme involving FMC playing a role as a middleman
between EPA and growers to ensure that carbofuran use in no one area
exceeds a certain percentage of the cropped area. FMC has properly
filed proposed amendments to its FIFRA registration, which would
incorporate these new restrictions on carbofuran use and EPA will
review these proposals consistent with the substantive and procedural
requirements of FIFRA. At such time as these new terms of registration
are determined by EPA to meet the standard for registration, and not
before, would it be appropriate for EPA to consider whether the
tolerance revoked by the May 15, 2009 rule should be re-established.
Finally, Petitioners argue that it can raise its proposed terms of
carbofuran use because EPA cannot limit them from putting forward new
issues in a hearing. As explained below, EPA believes Petitioners have
misconstrued the law on this point. However, even assuming for the sake
of argument that Petitioners are correct that new issues can be raised
at a hearing on objections, Petitioners admit that any newly raised
issues must meet the standard of relevance. As explained above,
however, objections based on terms or FIFRA registration proposed after
EPA's final rule are irrelevant to the correctness of EPA's
determination in that final rule.
EPA has nonetheless evaluated each of Petitioners' objections and
hearing requests and determined that there are alternate grounds for
denying them. (See Units VI.E through I). EPA has undertaken this
analysis for all of the objections despite the fact that it is not at
all clear that those of Petitioners'
[[Page 59624]]
claims which appear to be unrelated to FMC's recently proposed
registration amendments would either individually or collectively
change EPA's safety determination for the carbofuran tolerances given
the relatively high level of risk estimated for the carbofuran
tolerances in the final revocation rule. Petitioners have certainly not
provided any road map as to how a safety finding could be made absent
FMC's recently-proposed registration amendments. The failure to make
such a showing is further justification for EPA's denial of
Petitioners' objections and hearing requests.
D. Response to Petitioners' Objection That EPA Lacks the Authority To
Limit the Issues That May Be Raised in Objections and Hearing Requests
1. Response to Legal Issue. Petitioners claim that EPA lacks the
authority to restrict the issues that may be raised as part of their
objections. Specifically, they challenge EPA's interpretation that the
failure to raise issues or provide information during the comment
period on the proposed rule bars consideration of such issues or
evidence as part of submitted objections or hearings. Petitioners make
two arguments in support of this contention: (1) That neither FFDCA
section 408(g) on its face nor EPA's regulations implementing FFDCA
section 408(g) limit the issues that can be raised in objections, or in
any hearing; and (2) that even though the rulemaking phase is governed
by 553 of the Administrative Procedure Act (APA), the hearing must be
held in accordance with APA sections 556 and 557, which requires that
the ``exclusive record for decision must consist of testimony and
exhibits received at the hearing, as well as other papers filed in the
hearing proceeding'' (Obj at 64). On this basis, the Petitioners
conclude that all of the cases cited in the Final Rule requiring
parties to raise all issues and information on which they intend to
rely in subsequent proceedings are inapplicable.
These arguments are premised on several fundamental
misconstructions of the FFDCA section 408 and the APA. None of the
cases they cite address the specific question of whether and how the
requirements of section 553 of the APA apply to FFDCA section 408. And
for many of these cases, Petitioners misquote the cases, misinterpret
the holdings, or misconstrue language taken out of context.
Petitioners' first argument, that neither section 408(g) nor EPA's
regulations limit the issues that can be raised in objections or in any
hearing, is incorrect and misses the point. As discussed at length in
the Final Rule, the provisions of 408(g) are not to be viewed in
isolation, but as part of a coherent statutory structure inextricably
linked to the FFDCA's informal rulemaking procedures and section 553 of
the APA. Petitioners concede that FFDCA section 408 establishes an
informal rulemaking process (Obj at 62-63). As an informal rulemaking,
the process is governed by section 553 of the APA and the case law
interpreting these requirements, except to the extent that section 408
provides otherwise.\5\ In this regard, it is well established that the
failure to raise factual or legal issues during the comment period of a
rulemaking constitutes waiver of the issues in further proceedings.
E.g., Forest Guardians v. U.S. Forest Service, 495 F.3d 1162, 1170-1172
(10th Cir. 2007) (Claim held waived where commenters ``failed to
present its claims in sufficient detail to allow the agency to rectify
the alleged violation''); Nuclear Energy Institute v. EPA, 373 F.3d
1251, 1290-1291 (DC Cir. 2004) (``To preserve a legal or factual
argument, we require its proponent to have given the agency a `fair
opportunity' to entertain it in the administrative forum before raising
it in the judicial forum.'') Native Ecosystems Council v. Dombeck, 304
F.3d 886, 889-900 (9th Cir. 2002) (Purpose of requirement that issues
not presented at administrative level are deemed waived is to avoid
premature claims and ensure that agency be given a chance to bring its
expertise to bear to resolve a claim); Kleissler v. U.S. Forest
Service, 183 F.3d 196, 202 (3d Cir. 1999) (Policy underlying exhaustion
requirement is that ``objections and issues should first be reviewed by
those with expertise in the contested subject area''); National
Association of Manufacturers v. U.S. DOI, 134 F.3d 1095, 1111 (DC Cir.
1998) (``We decline to find that scattered references to the services
concept in a voluminous record addressing myriad complex technical and
policy matters suffices to provide an agency like DOI with a `fair
opportunity' to pass on the issue''); Linemaster Switch Corporation v.
EPA, 938 F.2d 1299, 1305-1306 (DC Cir. 1991) (declining to consider in
challenge to final rule, data alluded to in comments but not submitted
during the comment period, and information submitted to EPA office that
was not developing the rule).
---------------------------------------------------------------------------
\5\ For example, section 408(d) allows the Agency to proceed to
a final rule after publication of a submitted petition, rather than
requiring publication of a proposal.
---------------------------------------------------------------------------
Moreover, EPA clearly stated in the proposed rule that the Agency
considered that the usual requirements applicable to informal
rulemakings would remain applicable in this informal rulemaking. The
proposal explicitly noted that ``[i]f you anticipate that you may wish
to file objections on the final rule, you must raise those issues in
your comments on this proposal. EPA will treat as waived, any issue not
originally raised in comments on this proposal'' (73 FR 44,865 (July
31, 2008)).
The fact that FFDCA section 408 in certain limited circumstances
supplements the informal rulemaking with a hearing does not
fundamentally alter the requirements applicable to informal
rulemakings. Nor, as discussed below, does it convert this into a
formal rulemaking, subject to the exception in section 553. The FFDCA
section 408 establishes a unique statutory structure with multiple
procedural stages, and delegates to EPA the discretion to determine the
implementation that best achieves the statutory objectives.
Accordingly, EPA interprets the notice and comment rulemaking portion
of the FFDCA section 408 process as an integral part of the FFDCA
process, inextricably linked to the administrative hearing. The point
of the rulemaking is to resolve the issues that can be resolved, and to
identify and narrow any remaining issues for adjudication. Consequently
the administrative hearing does not represent an unlimited opportunity
to supplement the record, particularly with information that was
available during the comment period, but that commenters have chosen to
withhold. For example, as discussed at greater length in Unit VI.E.2,
both in their comments, and again in their objections, the Petitioners
failed to provide the underlying mathematical modeling that supported
their claim that the appropriate children's safety factor was 1X,
rather than 4X. Instead, they presented only summary results.
Similarly, although the Petitioners claimed in their comments to have
conducted an alternate analysis showing that aggregate carbofuran
exposures to children would be safe, they failed to provide the data
and details of that assessment to the Agency. They also failed to
provide several critical components that served to support key inputs
into that assessment.
To read the statute otherwise would be to render the rulemaking
portion of the process entirely duplicative of the hearing, and thus,
ultimately meaningless. See, e.g., FDA v. Brown & Williamson Tobacco,
529 U.S. 120, 132-133 (2000) (Court must interpret statute as a
symmetrical and coherent regulatory scheme, and fit, if possible,
[[Page 59625]]
all parts into a harmonious whole.) APW, AFL-CIO v. Potter, 343 F.3d
619, 626 (2nd Cir. 2003) (``A basic tenet of statutory construction * *
* [is] that a text should be construed so that effect is given to all
its provisions, so that no part will be inoperative or superfluous,
void or insignificant, and so that one section will not destroy another
* * *''), quoting Silverman v. Eastrich Mulitple Investor Fund, 51 F.3d
28, 31 (3rd Cir. 1995). The equities of this construction are
particularly strong, where, as here, the information was (or should
have been) available during the comment period. See, Kleissler, 183
F.3d at 202 (``[A]dministrative proceedings should not be a game or a
forum to engage in unjustified obstructionism by making cryptic and
obscure reference to matters that `ought to be' considered and then,
after failing to do more to bring the matter to the agency's attention,
seeking to have that agency determination vacated'') citing Vermont
Yankee Nuclear Power Corp. v. NRDC, 435 U.S. 519, 553-54 (1978). For
example, one of Petitioners' exhibits is the drinking water modeling
that served as the basis for the comments submitted on the proposed
rule. The documents are dated well before the close of the comment
period, and were clearly available for submission along with the
comments (Exhibit 15). Yet they were only provided to EPA as part of
the Petitioners' objections.
Contrary to Petitioners' contention, EPA's interpretation is
entirely consistent with the FFDCA's language and structure. The fact
that the statute and regulations allow ``any person'' to file
objections is immaterial. At issue is not ``who'' may raise objections,
but what issues may be raised as part of the objections to justify a
hearing. And on the relevant question, the statute is clear that only
certain issues--those of material fact--may be raised in objections to
justify a hearing (21 U.S.C. 346a(g)(2)(B)). EPA's regulations expand
on this limitation, providing, among other requirements, that hearings
will not be held on legal or policy issues, nor on the basis of mere
allegations, nor where EPA concludes that the data and information
submitted, even if accurate, would be insufficient to justify the
factual determination urged (See 40 CFR 178.32). It is true that FFDCA
section 408(g)(2)(A) provides little guidance on the objections that a
party may raise, requiring only that parties identify the specific
provisions challenged, and state ``reasonable grounds'' for their
objection. But the relative silence of the statutory provision does not
mean that EPA is required to allow parties to raise any and all
objections; rather it means that Congress left the question of what
constitutes ``reasonable grounds'' for EPA to resolve.
In construing that requirement, EPA gives weight to the fact that
408(g) is only one part of a larger, multi-stage, administrative
process, and that the statute does not support an interpretation that
this one phase be granted greater significance than the rest of the
process. Also relevant is that Congress delegated broad discretion to
the Agency to determine whether a hearing is ``necessary'' (21 U.S.C.
346a(g)(2)(B)). Accordingly, EPA believes that whether an objection
states ``reasonable grounds'' is to be measured against the context of
the rulemaking, and the provisions applicable to hearing requests.
Fundamentally, FFDCA section 408 delegates broad discretion to EPA,
both to determine how best to harmonize the statutory process and to
determine what constitutes ``reasonable grounds'' for objections.
Consequently, the relevant question is whether EPA's exercise of
discretion in requiring parties to present all available factual issues
and evidence during the rulemaking is reasonable. It is undeniably a
reasonable exercise of discretion to ensure that the rulemaking is not
an opportunity for one party to waste the time and resources of all
parties--both the government and other rulemaking participants--by
failing to raise all of their issues or withholding information for the
purpose of surprising the government at a later point during the
proceeding. See, e.g., Vt. Yankee, 435 U.S. at 553-554; United States
v. L.A. Tucker Truck Lines, 344 U.S. 33, 37 (1952) (``courts should not
topple over administrative decisions unless the administrative body * *
* has erred against objection made at the time appropriate under its
practice'').
EPA has consistently interpreted section 408 in this fashion since
the 1996 amendments. For example, EPA previously ruled that a
petitioner could not raise new issues in filing objections to EPA's
denial of its Original petition. See 72 FR 39318, 39324 (July 18, 2007)
(``The FFDCA's tolerance revocation procedures are not some sort of
`game,' whereby a party may petition to revoke a tolerance on one
ground, and then, after the petition is denied, file objections to the
denial based on an entirely new ground not relied upon by EPA in
denying the petition.''). EPA reasoned that new issues were not
cognizable because they ``not an objection to the `provisions of the *
* * order [denying the petition]' '' (Id.). Similarly, in a recent
decision EPA denied NRDC's request for a hearing because they had
failed in their original petition to raise the claim asserted in their
objection (73 FR 42683, 42696 (July 23, 2008)). EPA noted that although
NRDC did argue in its petition that EPA cannot make a safety finding
without completing the endocrine screening program under FFDCA section
408(p), it did not assert claims regarding the endocrine data and the
children's safety factor. Citing its previous decision, EPA denied
NRDC's objections and hearing requests as to the children's safety
factor (Id.). In that same decision, EPA also denied a number of
hearing requests on the ground that requestor failed to proffer
supporting evidence; EPA opined that a failure to offer evidence at an
earlier stage of the administrative proceeding could not be cured by
suddenly submitting such evidence with a hearing request. (See 73 FR
42683, 42710 (July 23, 2008) (``Presumably Congress created a multi-
stage administrative process for resolution of tolerance petitions to
give EPA the opportunity in the first stage of the proceedings to
resolve factual issues, where possible, through a notice-and-comment
process, prior to requiring EPA to hold a full evidentiary hearing,
which can involve a substantial investment of resources by all parties
taking part * * * Accordingly, if a party were to withhold evidence
from the first stage of a tolerance petition proceeding and only
produce it as part of a request for a hearing on an objection, EPA
might very likely determine that such an untimely submission of
supporting evidence constituted an amendment to the Original petition
requiring a return to the first stage of the administrative proceeding
(if, consideration of information that was previously available is
appropriate at all'').
The two cases Petitioners cite that are specific to section 408(d)
do not alter this assessment. Neither of those cases addressed the
scope of the evidence that could be properly raised as part of
objections to justify a hearing. Nor were the courts examining the
extent of EPA's authority to impose requirements on the filing of
objections under 408(g). Rather these courts were evaluating the scope
of the FFDCA's exclusive review provisions, and whether the plaintiffs
could bring a challenge to EPA policies and individual tolerance
decisions without first exhausting the FFDCA's petition process.
Geertson Farms v. Johanns, 439 F.Supp.2d 1012, 1022-1023 (N.D. Ca
2006); NY v. EPA, 350 F.Supp.2d 429, 442-443 (S.D.N.Y. 2004). This
issue is not identical to the questions at issue here: for example, the
[[Page 59626]]
court in Geertson Farms held that the plaintiffs' procedural and policy
decisions were properly raised initially before the Agency through the
petition process. 439 F.Supp2d at 442. Yet it is undeniable that EPA's
regulations preclude the reliance on policy or legal issues as a
justification for an Agency hearing.
Nor do the Petitioners' other cases compel a different result. The
majority of the Petitioners' cases concern FFDCA section 701(e), which
differs in several significant respects from FFDCA section 408. Section
701(e) imposes no requirements whatsoever on the party submitting the
objection: ``any person may file objections * * * specifying the
provisions of the order deemed objectionable, stating the grounds
therefore * * *'' 21 U.S.C. 371(e)(2). This section also expressly
provides that FDA must hold a hearing upon request: ``As soon as
practicable after such request for a public hearing, the Secretary,
after due notice, shall hold such a public hearing for the purpose of
receiving evidence relevant and material to the issues raised by such
objections.'' 21 U.S.C. 371(e)(3). In the face of this language, it is
unsurprising that the courts held that FDA lacked discretion to deny a
hearing. Further, under FFDCA section 701(e) the mere filing of an
objection automatically stays the effectiveness of the challenged
provisions. ``Until final action is taken upon such objections is taken
by the Secretary under paragraph (3), the filing of such objections
shall operate to stay the effectiveness of those provisions of the
order to which the objections are made.'' 21 U.S.C. 371(e)(3). By
contrast, section 408 grants the Administrator the discretion to stay
the effectiveness of the regulation if objections are filed. 21 U.S.C.
346a(g)(1). Indeed, the Petitioners' own cases specifically distinguish
between section 701(e) and other FFDCA provisions. See Pactra
Industries v. Consumer Product Safety Commission, 555 F.2d 677, 685
(9th Cir. 1977) (rejecting FDA argument that FFDCA section 701 should
be read consistently with FFDCA sections 505 and 507 to allow for
summary judgment procedures).
Petitioners' second argument is equally incorrect.\6\ As an initial
matter, the parties agree that FFDCA 408 establishes a hybrid
rulemaking procedure, with informal rulemaking initiating, and
frequently ending, the process (74 FR 23070 (May 15, 2009)); Obj at
62). Hybrid rulemaking is not formal rulemaking, which is the only
rulemaking to which APA sections 556 and 557 apply. Nevertheless,
Petitioners contend that once objections are raised, ``Congress
required the use of a formal rulemaking procedure involving an on-the-
record hearing for resolving factual disputes.'' (Obj at 62) Nothing in
the FFDCA section 408 or the APA supports this interpretation. And the
cases cited in support of this argument are inapposite or misconstrued.
---------------------------------------------------------------------------
\6\ As discussed below, it is not clear that a determination
that a hearing, if held, must be held in accordance with APA
sections 556 and 557 precludes EPA from exercising its discretion to
restrict the issues and evidence that may be raised at this final
stage of the administrative process.
---------------------------------------------------------------------------
The APA section 553 on its face applies to all rulemakings except
``[w]hen rules are required by statute to be made on the record after
opportunity for an agency hearing'' (5 U.S.C. 553(c)). Under this
language, APA section 553 will apply unless two requirements are met:
(1) The statute requires an opportunity for a hearing as part of the
rulemaking, and (2) the hearing is required to be ``on the record.''
FFDCA section 408 hearings are neither ``required,'' nor mandated to be
``on the record.'' The case law is clear that statutes containing both
characteristics are the hallmark of formal rulemaking, and that formal
rulemaking is the rare exception. AT&T v. FCC, 572 F.2d 17, 21-23 (2d
Cir. 1978) (``The APA requires trial-type hearings only `[w]hen rules
(or adjudications) are required by statute to be made (or determined)
on the record after opportunity for an agency hearing.' '') (citations
omitted); Minden Beef Co v. Cost of Living Council, 362 F.Supp. 298 (D.
Neb. 1973) (examining whether statutory provision that ``[t]o the
maximum extent possible, the President or his delegate shall conduct
formal hearings * * *'' makes hearings mandatory, in determinating
whether formal rulemaking required). See also, e.g., Girard v.
Klopfenstien, 930 F.2d 738, 741 (9th Cir. 1991) (``The APA does not
apply because a debarment hearing is not required by statute. The fact
that the hearing is `on the record' does not trigger an application of
the formal adjudication provisions of section 554 of the APA'');
Smedberg Machine & Tool v. Donovan, 730 F.2d 1089, 1092-93 (7th Cir.
1984) (holding section 554 inapplicable to a proceeding that ``gives
the adminsitrative law judge the discretion, rather than the obligation
to conduct a review hearing.''). As discussed below, in contrast to
other sections of the FFDCA, such as section 701(e), FFDCA section 408
makes clear that a hearing is not mandatory upon request, but that EPA
has broad discretion to determine whether a public hearing is necessary
to receive factual evidence. See, 21 U.S.C. 346a(g)(2)(B),
346a(g)(2)(C). See also, H.R. Rep. No. 104-669, at 49 (1996).
The Supreme Court made clear in Florida East Coast Railway v. FLRA,
that the circumstances under which rules are ``required to be made on
the record after opportunity for an agency hearing'' are limited to
those where Congress clearly indicates the intent to do so. 410 US 224,
241 (1973). The mere fact that statute offers an opportunity for an
agency hearing is not sufficient to bring rulemaking under scope of
this exemption. Id. See also, U.S. v. Allegheny-Ludlum Steel, 406 U.S.
742 (1972); NRA v. Brady, 914 F.2d 475, 485 (9th Cir. 1990) (No oral
hearing required where statute required Secretary to ``afford
interested parties opportunity for hearing'' and Agency regulations
reserved right to determine whether oral hearing warranted); Wisconsin
Gas Co v. FERC, 770 F.2d 1144, 1165-1168 (DC Cir. 1985) (APA 556
hearing not required when statute only contained provisions requiring
decision ``after a hearing'' and ``substantial evidence'' standard of
judicial review); AT&T v. FCC, 572 F.2d 17, 21-23 (2d Cir. 1978) (APA
556 hearing not required when statute only contained provisions
requiring decision ``after a hearing'' and ``substantial evidence''
standard of judicial review) Philips Petroleum Co v. FPC, 475 F.2d 842,
851-852 (10th Cir. 1973) (formal rulemaking not required even though
statute required ``full hearing'' and Agency traditionally conducted
trial-type adjudicative hearing).
Unless the statute providing for agency action prescribes
``hearings on the record,'' either in those exact words or by using
similar words to indicate that Congress specifically intended to impose
the full trial-type requirements of sections 556 and 557, the statute
does not fall within section 553's exception. FL East Coast Railway,
410 US at 241. While the absence of those words is not dispositive,
``in the absence of these magic words, Congress must clearly indicate
its intent to trigger the formal, on the record hearing provisions of
the APA.'' City of West Chicago, Illinois v. NRC. 701 F.2d 632, 641
(7th Cir. 1983) (citations omitted). See also, e.g., National
Classification Committee v. ICC. 765 F.2d 1146, 1150-1151 (DC Cir.
1985) (``Thus under Florida East Coast, there is a strong presumption
that the procedural guarantees of section 553 of the APA are sufficient
unless Congress specifically indicates to the contrary'' citing Vermont
Yankee Nuclear Power Corp v. NRC, 435 U.S. 519 (1978)); AT & T v. FCC,
572 F.2d at 21-23 (``The words, `on the record' have become, as the
District of Columbia Circuit has
[[Page 59627]]
observed, a `touchstone test' for the applicability of the APA's trial-
type procedures''); Philips Petroleum Co, 475 F.2d at 851-852 (``The
fact, as previously noted, that the Gas Act does not contain the words
`on the record' furnishes a strong argument in support of the
Commission's contention that informal rulemaking satisfies the
requirements of the APA''); Minden Beef Co, 362 F.Supp. at 306-307
(``Requiring `formal hearings' is not identical with requiring that
rules be made on the record after opportunity for agency hearing.'')
What is notable is that, in all cases, the court required clear
expression that Congress specifically intended to impose full trial-
type requirements.
Thus the question is whether Congress indicated any intent to
entirely remove the FFDCA section 408 process from the requirements of
553. The mere fact that FFDCA section 408 requires some (or even many)
of the procedures applicable under section 556 and 557 does not resolve
the question. See, e.g., National Classification Committee v. U.S., 765
F.2d 1146, 1150-1151 (DC Cir. 1985) (Rejecting argument that formal
rulemaking required on grounds that ``[u]nder Florida East Coast there
is a strong presumption that the procedural guarantees of section 553
of the APA are sufficient unless Congress specifically indicates to the
contrary''); Association of National Advertisers v. FTC, 627 F.2d 1151,
1165-1168 (DC Cir. 1979) (formal rulemaking not required, even though
statute ``did order use of procedures not required in informal
rulemaking'' such as rights to rebuttal and cross-examination at public
hearing.); American Public Gas Association v. FPC, 567 F.2d 1016, 1065-
1067 (DC Cir. 1977) (Formal rulemaking not required by statutory
provisions requiring ``full hearing'' and ``substantial evidence''
standard of judicial review).
In fact, the language and legislative history of section 408
provide clear indication of Congressional intent not to subject
proceedings under these sections to APA sections 556 and 557. FFDCA
section 408 does not reference APA sections 556 or 557 (see, e.g., 7
U.S.C. 136d(c)(2)). By contrast, the previous version of section 408
did reference APA section 556, and the deletion of this requirement
provides clear evidence of Congressional intent not to exempt FFDCA
from APA 553. Prior to the 1996 amendments, section 408(d)(5) of the
original act, which governed the conduct of hearings, specifically
referenced APA 556. (``Any report, recommendations, underlying data,
and reasons certified to the Secretary by an advisory committee shall
be made part of the record of the hearing, if relevant and material,
subject to the provisions of section [556] of the APA.''). 21 U.S.C.
346(d)(5). Moreover, the previous version of the statute contained
additional language consistent with the requirement of hearings subject
to APA sections 556 and 557; for example, the previous version of
section 408(d)(5) repeatedly makes reference to ``testifying at such
hearing.'' A further consideration is that several other provisions of
the FFDCA do explicitly reference APA sections 554 or 556. Compare, 21
U.S.C. 333(g)(3) (``A civil penalty * * * shall be assessed by the
Secretary by an order made on the record after opportunity for a
hearing provided in accordance with this subparagraph and section 554
of title 5''); 21 U.S.C. 342(f)(1)(C) (requiring the Secretary, upon
any declaration of imminent hazard under this section to ``initiate a
proceeding in accordance with sections 554 and 556 of title 5''). The
fact that Congress chose not to explicitly reference APA sections 556
or 557 provides a strong indication that they did not intend to impose
such a requirement on section 408 proceedings. See, e.g., St Louis Fuel
and Supply Co v. FERC, 890 F.2d 446, 449 (DC Cir. 1989) (holding that
formal hearing under APA 554 not required on that grounds that ``[w]e
consider it significant that, unlike section 7193(c), other
prescriptions in the DOE Organization Act expressly invoke the APA'')
(citations omitted).
Nor does any provision of FFDCA section 408 include the requirement
that the hearing be ``on the record.'' By contrast, several other
provisions of the FFDCA include that exact phrase. Compare, 21 U.S.C.
335a(i) (``The Secretary may not take action * * * unless the Secretary
has issued an order for such action made on the record after
opportunity for an agency hearing on disputed issues of material
fact.''); 21 U.S.C. 335b(b)(1)(A) (``A civil penalty shall be assessed
* * * by an order made on the record after an opportunity for an agency
hearing * * *''); 21 U.S.C. 335(c)(b) (``The Secretary may not take
action * * * unless the Secretary has issued an order for such action
made on the record after opportunity for an agency hearing on disputed
issues of material fact.'') Under all rules of statutory construction,
those differences are presumed to be intentional. Russello v. United
States, 464 U.S. 16, 23 (1983) (``[W]here Congress includes particular
language in one section of a statute and omits it in another section of
the same Act, it is generally presumed that Congress acts intentionally
and purposely in the disparate inclusion or exclusion'').
Equally significant is that the language of section 408 explicitly
grants EPA broad discretion to deny a hearing. Section 408(g)(2)(B)
provides that EPA shall ``hold a public evidentiary hearing, if and to
the extent the Administrator determines that such a public hearing is
necessary to receive factual evidence relevant to material issues of
fact raised by the objections'' (21 U.S.C. 346a(g)(2)(B)) (emphasis
added). This language grants EPA the discretion to determine whether
the issues raised in objections are ``material'' issues of fact.
Further, even where evidence relevant to an issue of material fact is
proffered (essentially the standard set forth in 40 CFR 178.32), EPA
construes the statutory language as requiring it to hold a hearing only
where it determines it is necessary to receive proffered evidence. In
other words, the statute grants EPA the discretion to determine that
the issues could be resolved entirely on the basis of the existing
written record. See Philips Petroleum, 475 F.2d at 848-849 (Formal
rulemaking under APA 556 not required even though statute required that
hearing be held, but ``Commission has a very broad discretion in
determining the form of its proceedings'').
EPA's construction is confirmed by the House Commerce Committee
Report accompanying the final bill, which states:
New subparagraph (g)(2)(B) allows an objector to request a
public evidentiary hearing. The Administrator would decide whether
[a] hearing were necessary to receive factual evidence relevant to
material issues of fact raised by the objections. The Committee
expects EPA to use this discretion fairly and to grant hearings to
responsible parties on all sides.
H.R. Rep. No. 104-669, at 49 (1996) (emphasis added). Notably, in
an earlier version of the 1996 amendments, the House bill provided for
a mandatory hearing during the notice-and-comment rulemaking stage of
an EPA-initiated proceeding. [H.R. 1627, 104th Cong. Section 405 (new
FFDCA section 408(e)(2)) (``EPA shall provide an opportunity for a
public hearing * * *'') (emphasis added). This requirement was dropped
prior to enactment but the contrast with section 408(g)(2)(B) confirms
the discretionary character of the latter.
If this were not sufficient indication of Congressional intent,
further evidence is provided by the fact that in amending section 408,
Congress chose not to adopt the provisions of section 701(e) that
Petitioners cite in their objections. Clearly, Congress could have
[[Page 59628]]
adopted the same provisions found in FFDCA 701(e), or in any of the
other comparable FFDCA provisions discussed above, but chose not to do
so.
EPA agrees that, when a hearing is warranted, the FFDCA requires an
evidentiary hearing that comports with the procedures contemplated by
408(g)(2)(B). But that is not the same as a requirement that section
553 be inapplicable to the proceedings, or that any hearing be held in
accordance with APA sections 556 and 557.\7\ Rather, section 408's
provisions are consistent with APA sections 553 (b) and (c), which
recognize the potential for hearings as part of informal rulemaking:
``Except when notice or hearing is required by statute, * * * the
agency shall give interested persons an opportunity to participate in
the rule making through submission of written data, views, or
arguments, with or without the opportunity for oral presentation.'' 5
U.S.C. Sec. 553(b)(c) (emphasis added).
---------------------------------------------------------------------------
\7\ EPA's regulations currently provide for a trial-type
adjudicatory hearing. These regulations were adopted under the
preceding statutory provision, and EPA has not yet undertaken any
effort to revise the regulations to take into account the revised
provisions of section 408.
---------------------------------------------------------------------------
Finally, Petitioners' citation to case law interpreting FFDCA
section 701(e) does not compel a different result. Petitioners claim
that the provisions of FFDCA 701(e) are ``near identical'' to those
under section 408, and on this basis, argue that, ``by analogy'' these
decisions compel an identical interpretation of the requirements of
FFDCA section 408 (Obj at 65). Petitioners are correct that section
701(e) of the FFDCA has been held to be ``one of those statutes, few in
number, that does require rule-making hearings to be on the record in
accordance with APA sections 556.'' Pactra, supra, 555 F.2d 677, 685
(9th Cir. 1977), citing Florida East Coast Railway, 410 U.S. at 237-38,
(dictum). But in all other regards, Petitioners are incorrect.
As previously discussed, there are several significant differences
between the statutory language of FFDCA sections 701 and 408 that
render Petitioners' citation to these cases inapposite. Hearings are
mandatory upon request under section 701, and the filing of objections
operates to automatically stay the provisions of the rule. Section
701(e)(2) requires only that the objection ``state the grounds
therefore,'' rather than requiring the a statement of ``reasonable
grounds.'' See Pactra at 684 (distinguishing FFDCA section 701(e) from
507(f) because the latter requires hearing applicants to show
`reasonable grounds'). Further, although section 701 does not itself
contain the requirement that the hearing be ``on the record,'' the
legislative history of this provision indicates that Congress intended
such hearings to be ``on the record.'' Pactra, 555 F.2d at 682-684
(detailing FFDCA section 701 legislative history). These
characteristics played a significant role in the court's decision that
FDA lacked the authority to deny hearings under section 701(e) on the
basis of summary judgment proceedings.\8\ However, as shown above, the
legislative history of section 408 provides a clear indication of a
contrary Congressional intent with respect to hearings under this
section.
---------------------------------------------------------------------------
\8\ Contrary to Petitioners' allegation, the DC Circuit has not
``arrived at the same conclusion'' (Obj at 65). All of the
discussion from Independent Cosmetic Manufacturers and Distributors
v. U.S. Dept of Health, Education, and Welfare presented in their
objections is dicta from a dissenting opinion. 574 F.2d 553, 572 (DC
Cir. 1978).
---------------------------------------------------------------------------
Petitioner's reliance on the ``substantial evidence'' standard in
FFDCA section 408(i) is equally misplaced. Incorporation of that
standard into judicial review provisions alone has been consistently
held to be insufficient to indicate Congressional intent to impose the
full requirements of APA sections 556 and 557 to a rulemaking.
Wisconsin Gas Co v. FERC, 770 F.2d at 1167 (``The procedures required
to develop this `substantial evidence' are not necessarily the strict
adversary procedures of sections 556 and 557 of the Administrative
Procedures Act''); Public Systems v. FERC, 606 F.2d 973, 979, n. 32 (DC
Cir. 1979) (substantial evidence requirement in Natural Gas Act
``carries no implications for procedures to be followed by the
Commission in compiling the record''); American Public Gas Association
v. FPC, 567 F.2d 1016, 1065-1067 (DC Cir. 1977) (``In our view,
however, this requirement [of the substantial evidence standard] in the
judicial review provision of the Act does not dictate the procedure to
be followed, or the nature of the hearing to be held).
The specific language of 408(i) defines the standard for the
reviewing court; it does not describe the process by which the agency
hearing is to be conducted. This is quite different from the language
under 501(c) of the CWA, on which the DC Circuit relied in holding that
hearings pursuant to APA section 554 were required. Marathon Oil v.
EPA, 564 F.2d 1253, 1262-1265 (DC Cir. 1977). The CWA section 501(c)
states ``[i]n any judicial proceeding * * * in which review is sought
of a determination under this chapter required to be made on the record
after notice and opportunity for a hearing * * *'' 33 U.S.C. 1369(c)
(emphasis added).\9\ By contrast, FFDCA section 408(i) merely provides
that ``[a]s to orders issued following a public evidentiary hearing,
the findings of the Administrator with respect to questions of fact
shall be sustained if supported by substantial evidence when considered
on the record as a whole'' (21 U.S.C. 346a(i)) (emphasis added). It is
also worth noting that the court expressly distinguished this case,
which dealt exclusively with an adjudicatory proceeding, from those
circumstances in which an agency proceeds through rulemaking. 564 F.2d
at 1262, n. 30.
In any event, even if section 556 did apply to hearings under
section 408, Petitioners cannot avoid the case law under section 553
and EPA's interpretation of the interrelationship between any hearing
granted under section 408(g)(2) and the rulemaking preceding it.
Petitioners cite to the general evidentiary provision in section 556(d)
that provides that only irrelevant or immaterial evidence may be
excluded and argue that this generic standard necessarily defines the
scope of a hearing regardless of the statutory scheme in which it is
embedded. However, context matters. As the DC Circuit noted, ``the
informal procedures of section 553 of the APA and the more formal
requirements of sections 556 and 557 are not mutually exclusive.''
American Public Gas Association, 567 F.2d at 1067. Even the caselaw
relied upon by Petitioners does not suggest that section 556(d)'s
evidentiary provision trumps all other considerations. Petitioners cite
primarily to Catholic Medical Center, Inc. v. NLRB, 589 F.2d 1166, 1170
(2d Cir. 1978). In that case, the Second Circuit interpreted section
556(d) as specifying that ``an agency thus may not provide for the
exclusion of evidence not protected by a privilege or countervailing
policy . * * *'' Id. (emphasis added). Here, EPA has interpreted its
authority to impose such a countervailing policy. Moreover, EPA's
interpretation is clearly within the broad discretion granted it by the
statute and the policy underlying the interpretation is a reasonable
adaptation of judicial practice with regard to issues not presented in
notice and comment rulemaking proceedings. Thus, Petitioners' technical
and formalistic argument concerning section 556(d), which ignores the
context of the section 408(g)(2) hearing provision, must be rejected.
Similarly unavailing is Petitioners' argument concerning section
556(e)'s
[[Page 59629]]
specification that the ``exclusive record for decision'' after a
hearing is material or testimony submitted in the hearing or hearing
proceeding. Petitioners assert that this provision somehow removes any
limitations on what can be submitted at the hearing because ``that
`exclusive record' is independent of whatever record may exist in the
prior informal rulemaking * * *.'' (Obj at 64). Yet the hearing record
is not ``independent'' of the rulemaking record in that EPA regulations
require that the rulemaking record be included in the record of the
hearing (40 CFR 179.179.83(a)(1)). Once again, Petitioners' argument
fails because it considers section 556 in isolation rather than taking
into account the context of the entire administrative proceeding in
which the hearing is embedded.
Finally, Petitioners complain that EPA ``raised a host of new
issues and assertions for the first time in the Final [rule],'' and it
would be inequitable for EPA to prevent them from raising objections on
these new assessments. Petitioners identify ten categories of ``new
computations and contentions'' that they claim raise issues that go
beyond those addressed in their prior comments. With one exception, all
of these ``new computations and contentions'' were revisions to
analyses conducted in response to Petitioners' comments. Indeed, some
of these were revisions undertaken in response to Petitioners' specific
request; for example, the ``new'' BMD analyses they identify were: (1)
Corrections made in response to an EPA error identified in their
comments; (2) an extrapolation of BMD50 s, using the dose-
time-response model, to develop a common point of comparison between
all studies, which they had claimed was the appropriate approach; and
(3) a calculation generating a new dose-response model in order to
calculate the BMD50 s for brain and RBC AChE inhibition, in
response to Petitioners' claim that failure to do so was inappropriate
(Refs. 24, 25, 85). Since these analyses were done at their behest,
they can hardly complain that they present new issues on which they had
no opportunity to comment. The Agency's underlying methodologies were
the same as those used for the proposed rule; the analyses were based
on information provided by the Petitioners and/or to address the
revisions requested as part of the Petitioners' comments.
Regarding the remaining analyses: The ``new exposure estimates for
ground and surface water,'' as well as the ``revised dietary risk and
drinking water assessments'' and ``new assessment of the impact of
buffers and setbacks'' were conducted to accurately reflect the use
under the registration, as modified by FMC's cancellation of uses and
additional mitigation measures. The same is true for the ``new analysis
of the various carbofuran labels;'' the analysis related to the labels
submitted as part of the September 2008 comments. The chlopyrifos
studies were raised in response to the Petitioners' citation to a
subset of chlorpyrifos data. They acknowledge that the ``new literature
citations'' were provided to address one of their contentions (Obj at
56). The sole exception relates to EPA's calculation of carbofuran-
specific half-lives for use in the dietary risk assessment. As
discussed in Unit VI.G.2, EPA does not reject Petitioners' challenge to
EPA's calculation of the 186-minute half-life on the basis that it is
untimely.\10\
---------------------------------------------------------------------------
\10\ The Petitioners' claim that ``EPA provided new information
concerning the raw data collected and records maintained by ORD in
relation to its toxicology studies'' is inaccurate. EPA provided no
new information on this topic in the final rule.
---------------------------------------------------------------------------
A fair indication that EPA has not raised a host of new issues in
the final rule is that, with the exception of the revised half-lives,
Petitioners do not challenge the substance of any of the allegedly
``new'' information. Indeed, as discussed in the sections below,
Petitioners have in many instances failed to address any of the
explanations or revised analyses EPA presented in the final rule.
Ultimately, Petitioners' complaint misses the point. EPA does not
interpret the statute and regulations to preclude the submission of any
new information as part of the objections phase. Such a position would
in fact be inconsistent with EPA's own regulations and past practice,
which require that in order to support a hearing request, a party
submit more than ``mere allegations or denials'' (40 CFR 178.32(b)(2)).
Rather, EPA's interpretation in this regard is analogous to the
determination of whether a final rule is the logical outgrowth of the
proposal and the comments. For example, EPA does not reject
Petitioners' citation to new studies in support of the contention that
RBC AChE data are generally more sensitive than PNS tissues on the
grounds that they are untimely. This is because these studies are
simply more evidence supplementing the issue they fairly raised in
their comments, and are intended to rebut EPA's response in the final
rule. Similarly, the submission of new analyses relating to the ground
water pH in Exhibit 14 is not considered untimely, as the issues they
raise relating to ground water pH were fairly raised in comments and
discussed throughout the rulemaking. Ultimately, EPA's policy is merely
that the objections phase does not present an opportunity for parties
to begin the process entirely anew, by raising issues or information
that could have been fairly presented as comments on the proposed rule.
Nor is the statute's additional procedural step an excuse to withhold
information that was clearly available at the time of the rulemaking.
2. Implications for FMC's Submission of New Registration Amendments
as Part of their Objections. On June 29, 2009, in conjunction with
their objections on the final rule, FMC Corporation submitted a request
for EPA to amend its registration in several regards. Some of the
requested amendments were further mitigation measures intended to
address carbofuran's dietary risks. The most significant of these was a
proposal intended to ensure that only 2% of any watershed would be
treated with carbofuran. The proposal would require that, within five
days of applying the product, all applicators report to FMC the
following information: The location that the product will be used,
crop, use rate, application method, acreage, and quantity applied.
Based on this information, FMC would track the percentage in each
watershed. ``Whenever it appears that carbofuran has been applied to
1.75% of any watershed,'' the registrant would report that information
immediately to EPA, ``cease further sales in any county that overlaps
with such a watershed for that use season, and shall attempt to recall
all unused carbofuran within such counties by offering to repurchase
such unused product'' (Exhibit 2). Additionally, FMC requested that its
registration be amended to require that ``based on watershed
boundaries, FMC * * * prior to each use season, allocate to its
distributors in a manner which will attempt to ensure that no
distributor receives more carbofuran for sale than can be accommodated
by the 2% watershed area cap in any watershed supplied by that
distributor.''
In addition, FMC proposed to add geographic restrictions that would
prohibit use in certain parts of the country. Specifically, they
proposed to restrict the use of carbofuran on potatoes to the three
states: Idaho, Oregon, and to select counties in Washington. They
proposed to restrict use on Sunflowers to only Colorado, Kansas,
Nebraska, and South Dakota, as well as limited portions of North Dakota
and Oklahoma. Under this proposal, use on corn would be restricted to
Colorado, Iowa, Illinois, Indiana, Kansas, Missouri, Nebraska, and
limited counties in Wisconsin. Further, they
[[Page 59630]]
proposed to add set-backs (i.e., areas where carbofuran could not be
applied) ranging between 100 and 1,000 feet from drinking water wells,
depending on the geographic area. Finally, as part of these amendments,
FMC also requested that EPA revise its registration to permit use of
carbofuran on pumpkins in Ohio, Illinois, and Indiana, and to cancel
the use on pumpkins in the southeastern United States.
As made clear in Unit VI.C., FMC's newly-proposed registration
amendments are irrelevant to the prior determinations made in the final
tolerance revocation rule. Further, as discussed in Unit VI.D., as a
consequence of the failure to raise these amendments measures as part
of their comments on the proposal, EPA considers that all issues
arising exclusively as a result of these proposed amendments have been
waived. There is no evident reason that FMC could not have offered
these amendments as part of its September 2008 proposals. All of the
information on which they rely was available in September of 2008. All
of the risk concerns that the amendments were intended to address were
discussed at length in EPA's proposed rule. Since 2006, EPA has clearly
stated its determination that carbofuran's potential to leach into
ground water and to runoff into surface water caused unacceptable
dietary risks. EPA's methodologies for evaluating these risks have not
changed since 2006. Indeed, EPA deferred regulatory action for several
months, subsequent to the Agency's determination in 2006 that
carbofuran did not meet either the FIFRA or FFDCA standard, to allow
the Petitioners time to generate data to address the exact same issues
these proposals are intended to address. In their comments on the
proposed rule, Petitioners provided some mitigation measures intended
to address issues relating to the carbofuran's leaching and runoff
potential: Well set-backs, buffers, geographic use restrictions, and
aerial application recommendations.
As previously discussed, EPA provided clear notice in the proposed
rule that issues that that were not raised during the comment period
would be considered waived in subsequent stages of the administrative
process (73 FR 44,865). Petitioners were well aware of this, as they
commented that ``EPA's requirement to raise all issues in the comments
does not appear to be legally binding'' (Ref. 18 at 118). Indeed they
acknowledged that they ``agree that identifying disputed issues in the
comments is efficient and desirable, and may help to narrow the issues
arising in subsequent objections and an administrative hearing.
Therefore, the commenters have made a good faith attempt to raise in
these comments the principal issues of which they are aware'' (Id.).
At this stage of the process, the statute requires the Petitioners
to object to the conclusions and provisions in EPA's final rule, not to
propose some new alternate license that they claim would meet the
statutory standards (21 U.S.C. 346a(g)(2)(A) (``any person may file
objections * * * specifying with particularity the provisions of the
regulation * * * deemed objectionable''). In fact, one might fairly
read their proposal as an admission that the existing license fails to
meet the statutory standards.
A further consideration is that the question of whether these
amendments can be approved depends on whether the Agency eventually
determines the amended registration meets the standards of FIFRA, which
include considerations beyond the dietary risks evaluated under the
FFDCA. Under FIFRA, the Agency's review of the amendments is also
subject to a statutorily mandated schedule (established as part of the
Pesticide Regulatory Improvement Act (PRIA)). These are no small
matters. In terms of timing, FMC explicitly acknowledged in its letter
submitting the proposed amendments that the amendments were subject to
the PRIA review process, requesting that the actions be subject to the
PRIA 8-month statutory deadline (which would establish a statutory
deadline of February 2010 for Agency consideration of FMC's
application). It is not clear whether FMC is arguing that its
application be accorded a higher priority than other applications and
be taken out of turn, or whether FMC is arguing that the consideration
of the objections and request for hearing must be delayed until the
FIFRA review process is completed. EPA rejects either position;
Petitioners cannot use this tolerance proceeding to evade FIFRA's
statutory review scheme, or use that scheme to delay this tolerance
proceeding.
As noted, although FIFRA incorporates the FFDCA dietary risk
standard, FIFRA also requires the Agency to evaluate a much wider scope
of issues in determining whether to grant new license requirements. For
example, EPA must evaluate the impact this proposal would have on
worker and ecological risks. In addition, EPA must carefully evaluate
the policy implications involved in authorizing Petitioners' scheme. In
this regard, it is worth noting that FMC's scheme is a novel one that
raises significant policy questions that are specific to FIFRA, such as
whether the steps proposed could be adequately enforced, which could
affect the confidence that everybody would, in fact, comply with all
the steps, (e.g., who would investigate whether users have properly
notified FMC of use of the product; would users have to keep records to
demonstrate to inspectors that they had appropriately reported use; how
would further sales in a county be prohibited); and whether the steps
themselves are appropriate tools from a policy perspective for dealing
with risks associated with the use of a pesticide (e.g., is it
appropriate to require users to report use to a pesticide manufacturer;
is such reporting subject to approval under the Paperwork Reduction
Act; is it appropriate public policy to limit sales in a watershed so
that some growers may have preferential access to a product; would the
scheme encourage early and potentially unnecessary purchase of product
by users; under what circumstances, if any, should EPA approve label
and license conditions that require the extra vigilance that would be
required here of users, distributors, and state and federal
regulators). Even if this scheme were determined independently to meet
the FFDCA safety standard, if ultimately EPA were unable to grant the
amendment based on the other considerations that it must evaluate under
FIFRA, the unacceptable dietary risks would still remain. Thus, whether
this scheme could result in a determination that the dietary risks are
acceptable is not ultimately severable from the larger FIFRA process.
Nor would it be appropriate to attempt to resolve FIFRA issues in a
hearing under the FFDCA.
Indeed it is questionable whether consideration of the proposed
amendments would be appropriate even under Petitioners' position that
all objections made in good faith may be presented at this stage of the
proceeding (Obj at 61). For example, less than six months prior to
their recent submission, the Petitioners proposed voluntarily
cancellation of all use on pumpkins except in the Southeastern United
States, alleging that sales data demonstrated that carbofuran was
needed in the Southeastern U.S. In response to this amendment, which
was submitted as part of their comments on the proposed rule, EPA
analyzed the dietary risks based on this proposed use pattern for the
final rule. A request, mere months later, for additional use on
pumpkins in states with different geographic and weather conditions and
[[Page 59631]]
cancellation of the use in the Southeastern U.S., may fairly be
considered suspect--an action intended to delay the revocation process
by forcing the Agency to conduct yet additional analyses, rather than a
good-faith objection.
For all of these reasons, EPA has determined that reliance on these
proposed amendments as a basis for raising objections to the final
rule, or for requesting a hearing is not appropriate. Nevertheless, EPA
evaluated the individual objections premised on the newly requested
terms and conditions of registration. And in each case, the submitted
materials relating to these objections and hearing requests
independently failed to meet the statutory and regulatory requirements
to justify a hearing, as discussed in the Units below.
E. Response to Specific Issues Raised in Objections and Hearing
Requests Relating to EPA's Children's Safety Factor
To more fully understand Petitioners' objection and hearing request
with regard to EPA's choice of a 4X children's safety factor and EPA's
responses, a little background is helpful. Section 408 of the FFDCA
imposes a default additional safety factor for the protection of
infants and children, to take into account the fact that children are
frequently more sensitive to a pesticide's effects than adults. This
default 10X safety factor can only be revised if the Agency has
``reliable data'' to demonstrate that the alternative safety factor--or
no safety factor--``will be safe for infants and children'' (21 U.S.C.
346a(b)(2)(C)). In determining whether a different factor is safe for
children, EPA focuses on the three factors listed in section
408(b)(2)(C)--the completeness of the toxicity database, the
completeness of the exposure database, and potential pre- and post-
natal toxicity. In examining these factors, EPA strives to make sure
that its choice of a safety factor, based on a weight-of-the-evidence
evaluation, does not understate the risk to children. (Ref. 79). The
Agency's approach to evaluating whether sufficient ``reliable'' data
exist to support the reduction or removal of the statutory default 10X
is described below in Figure 1.
BILLING CODE 6560-50-P
[GRAPHIC] [TIFF OMITTED] TR18NO09.000
[[Page 59632]]
BILLING CODE 6560-50-C
EPA has consistently required that data comparing the AChE
inhibition in young rat pups (typically PND11) and adult rats be
submitted on AChE-inhibiting pesticides, such as carbofuran, to
determine the extent of children's potential sensitivity. The study
measures the levels of AChE inhibition in both potentially relevant
target tissues: The brain and either the PNS or red blood cell (RBC),
which serves as a surrogate for the PNS. EPA required these data from
FMC for carbofuran, and FMC on two occasions submitted the studies.
Both sets of data, however, were rejected by EPA as scientifically
flawed because they inaccurately measured the levels of RBC AChE.
Despite the invalidity of the two FMC studies as to RBC AChE, EPA
still has certain, limited RBC AChE data and other PNS-related data on
carbofuran from other studies. These other carbofuran data indicate the
following: (1) PNS-related effects (tremors) occur in pups as a result
of exposure to carbofuran at low doses; (2) juveniles are more
sensitive than adults to carbofuran based on brain measures; (3)
juveniles are more sensitive than adults to carbofuran based on RBC
AChE measures; and (4) the relative sensitivity of juveniles compared
to adults as to RBC AChE is significantly greater the relative
sensitivity of juveniles compared to adults as to brain AChE. It is
also noteworthy that the data in adult rats showed RBC AChE was
generally more sensitive to carbofuran's effects than brain AChE (RBC
AChE inhibition was higher than brain at every dose except the lowest),
although these data are of limited relevance, because they were
conducted on adult animals rather than pups, and adult responses are
frequently not predictive of children's responses. However, because the
available pup RBC AChE data from EPA-ORD did not involve testing at
doses that produced a sufficiently low level of inhibition, the data
were not sufficient to develop a PoD for juveniles based on RBC AChE.
Accordingly, in making its children's safety factor determination
for carbofuran, EPA was faced with three significant issues: (1)
Sufficient data on carbofuran that are routinely-required for AChE-
inhibiting pesticides to measure PNS effects was not available; (2)
available data measuring the levels of AChE inhibition in brain and RBC
indicated that juveniles were more sensitive than adults to carbofuran
and other carbofuran data indicated that PNS-related effects could
occur in pups at low dose levels; and (3) although the evidence on
carbofuran as to RBC AChE inhibition in juveniles indicated that
effects on juveniles' PNS might be the most sensitive endpoint, there
was not sufficient data to calculate a PoD (for use in determining the
safe dose or PAD) on these effects. Despite the incompleteness of the
toxicity database and the evidence indicating the potential for pre-
and post-natal toxicity at a very sensitive level, which indicate the
need to retain a children's safety factor, EPA nonetheless determined
that, because there was limited reliable data in juveniles, a full
statutory default 10X was not necessary to ensure that children's
exposures would be ``safe.'' EPA undertook a complex comparison of the
brain and RBC AChE data in juveniles and determined that the likely
increased level of sensitivity for RBC AChE inhibition is 4X. EPA thus
concluded that using an additional children's safety factor of 4X
applied to the PoD from data on brain AChE inhibition in juveniles
would protect infants and children.
1. Challenge to EPA's Scientific Basis for Retention of a 4X
Children's Safety Factor. Petitioners object to EPA's conclusion that
the lack of peripheral tissue data justifies retention of any portion
of the children's safety factor. Petitioners raise two claims in this
regard. First, they allege that a carbofuran PoD based on brain AChE is
adequately protective of PNS effects. Second, they claim that RBC AChE
inhibition data are not the best surrogate for PNS effects when brain
data are available, and therefore, these data are not an ``appropriate
surrogate for PNS effects'' and should not have been relied upon as the
basis for retaining any portion of the safety factor. In support of
these points, Petitioners submit summaries of the testimony they intend
to offer at a hearing, along with copies of published studies that they
allege provide evidence of the points raised in the testimony.
In essence, these two main issues overlap, particularly with
respect to the evidence submitted. Petitioners rely on the same studies
to support both points. However, they are presented below separately as
discrete issues in the interest of clarity. Supplemental to these two
main points, EPA has identified three separate allegations made by
Petitioners in support of this objection, which are also analyzed
individually in this section.
a. Objection/hearing request subissue: Whether a carbofuran PoD
based on pup brain AChE inhibition data alone is adequately protective
of PNS effects. Petitioners argue that by establishing the PoD on pup
brain AChE inhibition data, EPA has adequately accounted for all PNS
effects in pups without the need for an additional children's safety
factor. They argue that brain data will adequately protect against PNS
effects, based on the claim that the available data show that the brain
is equally sensitive or more sensitive than PNS tissue. In support of
this objection, Petitioners' submit the evidence contained in Exhibits
4 and 6. Exhibit 4 consists of a report by Kendall Wallace, PhD,
entitled ``Expert Report: Carbofuran FQPA Safety Factor,'' along with
published studies conducted with OP chemicals, and other NMC chemicals
(Ref. 17, 51, 53, 54, 59, 61, 62, 72). Exhibit 6 consists of a report
by Lucio Costa, PhD, entitled, ``Expert Report: Carbofuran's FQPA
Safety Factor and Interspecies Uncertainty Factor,'' as well as
published literature studies conducted with chlorpyrifos and
disulfoton, both OP pesticides, and a single study with propoxur, an
NMC pesticide.
i. Background. In the proposed tolerance revocation, EPA presented
its rationale for retention of a children's safety factor.
As explained in Unit IV.A, EPA uses a weight of evidence approach
to determine the toxic effect that will serve as the appropriate PoD
(or regulatory endpoint) for a risk assessment for AChE inhibiting
pesticides, such as carbofuran (Ref. 78). Neurotoxicity resulting from
carbofuran exposures can occur in both the central (brain) and
peripheral nervous systems (PNS). In its weight of the evidence
analysis, EPA reviews data, such as AChE inhibition data from the
brain, peripheral tissues and blood (e.g., RBC or plasma), in addition
to data on clinical signs and other functional effects related to AChE
inhibition. Based on these data, EPA selects the most appropriate
effect on which to regulate; such effects can include clinical signs of
AChE inhibition, central or peripheral nervous tissue measurements of
AChE inhibition or RBC AChE measures (Id). Due to the rapid nature of
NMC pesticide toxicity it is difficult to document effects in the PNS
or even AChE inhibition in the PNS and thus studies measuring AChE
inhibition in the PNS are very rare for NMC pesticides. Although RBC
AChE inhibition is not adverse in itself, EPA's policy is to use it as
a surrogate for inhibition in peripheral tissues when peripheral data
are not available. As such, RBC AChE inhibition provides an indirect
indication of adverse effects on the nervous system (Id.).
There are laboratory data on carbofuran for cholinesterase activity
in plasma, RBC, and brain from studies in
[[Page 59633]]
multiple laboratory animals (rat, mouse, dog, and rabbits). Among these
are three studies that compare the effects of carbofuran on PND11 rats
with those in young adult rats (i.e., `comparative AChE studies')
(Refs. 1, 2, 66). Two of these studies were submitted by FMC and one
was performed by EPA-ORD. An additional study conducted by EPA-ORD
involved PND17 rats (Ref. 63).
The studies in juvenile rats show a consistent pattern that
juvenile rats are more sensitive than adult rats to the effects of
carbofuran. These effects include inhibition of brain AChE in addition
to the incidence of clinical signs of PNS neurotoxicity, such as
tremors, at lower doses in the young rats. This pattern has also been
observed for other NMC pesticides, which exhibit the same mechanism of
toxicity as carbofuran (Ref. 81). The 2008 SAP, in its review of the
carbofuran draft NOIC, concurred with EPA that the brain AChE data
clearly indicate that the juvenile rat is more sensitive than the adult
rat (Ref. 36).
The Agency does not have any AChE inhibition data for carbofuran in
the PNS tissue of adult or juvenile animals. There is data on RBC AChE
inhibition, which is a surrogate for PNS tissue AChE inhibition, in
adult animals at both high and low doses, and RBC data in pups, but
only at doses causing greater than 50% AChE inhibition (a very high
level of inhibition). In adults, the data show that RBC is generally
more sensitive to the effects of carbofuran than the brain, but that at
the lowest dose tested, brain and RBC have similar sensitivity. In
pups, the available data at higher doses show that, like adults, RBC is
more sensitive than brain. For example, the EPA-ORD studies showed that
RBC AChE inhibition is more sensitive than brain AChE inhibition in
both PND11 and PND17 pups at the lowest dose tested. However, the
lowest dose (0.1 mg/kg) in both studies missed the lower portion of the
RBC AChE inhibition dose-response curve for pups. At the lowest dose,
PND 11 pups had approximately 40% brain and 53% RBC AChE inhibition
while PND17 pups had approximately 25% brain and 50% RBC AChE
inhibition. Consequently, the Agency does not have RBC AChE inhibition
data in pups at the low doses (i.e., those that cause only 10%
inhibition) that are relevant to risk assessment to serve as a
surrogate for PNS tissue data.
EPA explained that additional evidence for the sensitivity of the
PNS to carbofuran's effects comes from data in pregnant rats exposed to
carbofuran that showed clinical signs that may be indicative of
peripheral toxicity. Finally, EPA explained that data from other AChE
inhibiting pesticides show that direct measures of peripheral nervous
system (e.g., lung, heart, and liver AChE) can be more sensitive than
brain AChE inhibition. To help illustrate, EPA gave an example of
another chemical for which brain inhibition alone was not at all
predictive of toxicity, to help explain why the lack of carbofuran data
was so significant. The example given was fenamiphos (an OP pesticide),
where cholinergic toxicity (e.g., tremors, miosis, salivation) was
observed following inhibition of RBC, but not brain, even up to
maximally tolerated doses (McDaniel and Moser, Ref. 53).
Normally, EPA would regulate based on the most sensitive endpoint,
which in this case would appear to be the effects on children's PNS.
However, as discussed above, EPA lacked the information that would
allow it to establish a PoD (or regulatory endpoint) based on the
effects on children's PNS. EPA therefore established its PoD based on
the AChE inhibition in pup brain. Generally, by regulating based on pup
data, EPA would directly account for any additional sensitivity that
children might have, because the safe levels estimated from these data
would be the levels at which infants and children would be affected. In
such circumstances, EPA could reduce the children's safety factor.
But because EPA lacked the data on the PNS effects in pups at low
doses of carbofuran, which are most analogous to the exposures that
infants and children will receive from eating food with carbofuran
residues, the Agency could not be confident that assessing risk using
brain AChE inhibition would be protective of potential effects in the
PNS for infants and children. Accordingly, EPA determined that, even
though the Agency was relying on pup data, consistent with the
statutory mandate that an additional safety factor be applied to
account for children's increased sensitivity in the absence of
information affirmatively demonstrating that no such safety factor is
necessary, the Agency could not conclude that removal of the statutory
default 10X would be ``safe for infants and children.'' As some
information was available to characterize the effects on infants and
children, EPA concluded that the full default 10X was unnecessary, and
that it could safely reduce the factor to 4X.
Petitioners raised many of the same assertions in their comments on
EPA's proposed rule that they raise in their objections. For example,
the Petitioners claimed that because EPA relied on pup brain data, no
additional safety factor would be necessary to account for children's
increased sensitivity, because ``brain data are a better surrogate for
the PNS than RBC data.'' The comments also contended that RBC data are
problematic in a number of regards, e.g., they are more variable. They
also argued that EPA had generally relied exclusively on brain data for
other NMC pesticides, and that to require an additional safety factor
for carbofuran based on the lack of RBC AChE data was inconsistent with
those other decisions.
In the final rule and response to comments EPA responded to all of
the Petitioners' claims, and comprehensively restated its reasoning
that the lack of PNS inhibition data warranted retention of some
portion of the children's safety factor for carbofuran (74 FR 68694-
68695 (May 15, 2009)). In essence, EPA explained that Petitioners had
not presented any information that fundamentally altered the available
risk information before the Agency. Specifically, EPA concluded that,
given that (1) the EPA-ORD data clearly show that a surrogate measure
of the peripheral nervous system (RBC AChE) in juvenile rats is more
sensitive to the effects of carbofuran than brain AChE inhibition; (2)
clinical signs consistent with toxicity to the peripheral nervous
system were seen at very low doses of carbofuran; and (3) data from
other AChE inhibiting pesticides show that direct measures of
peripheral nervous system (e.g., lung, heart, and liver AChE) can be
more sensitive than brain AChE inhibition, the Agency could not be
confident that assessing risk using brain AChE inhibition would be
protective of potential effects in the peripheral nervous system for
infants and children.
ii. Denial of hearing request. EPA is denying Petitioners' hearing
request on this subissue because the evidence proffered, even if
established, is insufficient to justify the factual determination urged
(40 CFR 178.32(b)(2)). The totality of the evidence submitted fails to
demonstrate a reasonable possibility that exclusive reliance on
carbofuran brain data will be protective, largely because they have
failed to proffer any evidence on several points that are critical to
their argument. As such, the objection rests on speculation and mere
allegation, and a hearing will not be granted on this basis (Id. See,
e.g., 73 FR 42708 (July 23, 2008); 57 FR 6667, 6671 (February 27,
1991)).
It is important to remember that to obtain a hearing on EPA's
children's safety factor decision, Petitioners must proffer more than
evidence on whether
[[Page 59634]]
EPA erred, Petitioners must proffer evidence showing there is
``reliable data'' supporting the children's safety factor they urge.
Without the latter, their objection is immaterial because the default
position is retention of an additional 10X safety factor. Accordingly,
EPA has evaluated Petitioners' proffers on its children's safety factor
claims in terms of whether they are sufficient to provide the
``reliable data'' needed to justify the 1X safety factor that
Petitioners propose.
For purposes of resolving whether the statute requires the
retention of a children's safety factor, the critical issue is whether
sufficient data exists to determine the effects on children's
peripheral nervous systems from low doses of carbofuran. None of the
evidence submitted affirmatively addresses this question. As discussed
in more detail below, the only evidence proffered in support of this
objection was: (1) A subset of the available carbofuran data from adult
animals; and (2) data, primarily in adult animals, from other chemicals
to demonstrate that generally, reliance on brain data will be
protective of PNS effects, and therefore EPA can assume that the same
will hold true for carbofuran. However, the Petitioners have failed to
submit any data to demonstrate that the effects seen in adults will be
predictive of the effects in juveniles. They have also submitted no
evidence specific to carbofuran that demonstrates the effects of low
doses on children's peripheral nervous systems. This is critical
because the evidence they do proffer on other chemicals fails to
establish that as a general matter, reliance on brain data will always
be protective of the effects on the PNS. The majority of the evidence
in other chemicals actually proves that reliance on brain data is
frequently not protective of the effects on the PNS. And the remainder
of the evidence on this point, taken in the light most favorable to the
Petitioners, provides only equivocal support for Petitioners. Such
evidence, by itself, is insufficient to relieve the uncertainty that
remains with respect to carbofuran, based on the affirmative evidence
in carbofuran-specific data, showing that reliance on brain data may
not be protective. And such evidence, that entirely fail to address the
points that the statute makes central to a determination of the
appropriate children's safety factor, cannot justify a hearing.
When examined more closely, their overall evidentiary proffer is
even less impressive. As discussed, much of the evidence was conducted
in adult rats. Indeed the only evidence Petitioners submitted in
support of this objection that was specific to carbofuran's effects on
the PNS was data in adult rats. No evidence was submitted to
demonstrate that adult data are generally predictive of responses in
pups. Nor was any evidence submitted to support the assumption that
pups will respond to low doses of carbofuran in the same way as adults.
Thus their evidentiary proffer is effectively based on mere speculation
that adult data will be predictive of pup responses, which cannot
justify a hearing (40 CFR 178.32(b)(2)). As EPA previously explained in
the proposed and final rules, responses in adult rats are not
necessarily predictive of, or relevant to, responses in juveniles since
the metabolic capacity of juveniles is less than that of adults (73 FR
44864, 74 FR 23046). As such, juvenile rats can be more sensitive to
some toxic agents. Simply put, studies that only involve adult animals,
therefore, do not provide information on effects on the young, which is
the focus of the children's safety factor. No matter how much evidence
Petitioners can amass showing that brain AChE is protective of RBC AChE
in adult animals, that does not relieve the uncertainty concerning
potential sensitivity of PNS tissues in juvenile animals, particularly
when all of the existing carbofuran data shows that pups are more
sensitive than adults to the effects of carbofuran, and that clinical
signs consistent with toxicity to the PNS were seen in pups at very low
doses of carbofuran. Accordingly, in the absence of carbofuran data in
pup PNS tissues or a surrogate such as RBC data, the Petitioners'
evidentiary proffer fails to establish a reasonable possibility that
this issue could be resolved in their favor. A hearing is not
appropriate in such cases (40 CFR 178.32(b)(2)).
The central tenet of this objection is that regulating based on the
effects in the CNS will ensure that the PNS is protected. In this
regard, Petitioners do cite to studies in juvenile animals, but all of
them are conducted with chemicals other than carbofuran.\11\ Moreover,
the Petitioners' evidence fails to demonstrate that the PNS can never
be more sensitive than the CNS, or even that the PNS is typically less
sensitive than the CNS. Rather, the evidence shows only that the CNS
(brain) is sometimes more sensitive, and sometimes less sensitive than
the PNS, depending on the chemical involved. Because the data do not
show a consistent pattern, it indicates only that the relative
sensitivity between the central and peripheral nervous systems varies
depending on the chemical involved, which cannot establish that
exclusive reliance on brain data as a general proposition will always
be protective of PNS effects in pups. Nor can it establish that
reliance on the brain data will be protective of the PNS effects in the
case of carbofuran.
---------------------------------------------------------------------------
\11\ Most of the studies were conducted on OP chemicals, and
expressly caution against extending the results to NMC chemicals
such as carbofuran; a point also raised by Petitioners' own experts
(Ex 4, 6).
---------------------------------------------------------------------------
When data are not available for a specific chemical, conclusions
based on other chemicals can only be scientifically supported if it has
been demonstrated that the conclusion is always true. If, ``in some
cases,'' the conclusion is not true, then in the absence of data on the
specific chemical, the conclusion cannot be made for that chemical, and
uncertainty exists regarding the effects of the individual chemical.
Since there are no data on the effects of carbofuran in PNS tissues or
RBC data at low doses in pups, even assuming that they were able to
prove that for the specific chemicals identified, the CNS is sometimes
more sensitive than the PNS, significant uncertainty would remain
regarding carbofuran's effects on the PNS. This is because the only
evidence specific to the effects of carbofuran on the PNS at low dose
levels that can be used as a comparison with the brain AChE levels is
the adult RBC data.
This also affects the materiality of this objection. If the adult
RBC AChE data are not considered, as Petitioners suggest, no
carbofuran-specific data exists to demonstrate the level of AChE
inhibition in the PNS of either adults or pups at the low dose levels
relevant to risk assessment. Thus, even assuming Petitioners could
successfully establish every point they raise in this regard, the fact
still remains that a decision maker would have no data that provides
any information relating to the potential effects of carbofuran on a
child's PNS. Given that FFDCA section 408(b)(2)(C) compels the
application of a 10X safety factor in the absence of information to
account for the presumptive sensitivity of children, the lack of any
data bearing on carbofuran's PNS effects would require the Agency to
apply a 10X safety factor, rather than the 4X factor applied in the
final rule.
A further flaw in the Petitioners' evidence is that it is
internally inconsistent. Notwithstanding their allegations (discussed
in subissue b below) that RBC data are inherently unreliable and should
be discounted in favor of brain data, the carbofuran adult RBC data are
one of the primary pieces of evidence proffered to support the claim
that reliance on the carbofuran pup brain data will protect against all
[[Page 59635]]
potential PNS effects (Exhibit 4). As discussed in more detail below,
the Report cites to the carbofuran data with adult rats to conclude
that brain AChE inhibition correlated closely with RBC AChE inhibition.
``This was further substantiated by the study published by McDaniel et
al. (Ref. 54), where they report that the `lowest dose of carbofuran
(0.10 mg/kg) significantly decreased brain ChE activity but not RBC ChE
or motor activity' * * *'' (Id. at 4, 6). Yet having granted scientific
validity to the adult RBC data, they must also concede the relevance of
the EPA-ORD carbofuran pup RBC data, which clearly demonstrate that at
every dose tested, RBC AChE, and therefore the PNS for which it is a
surrogate, is more sensitive than the brain in juvenile rats exposed to
carbofuran. They raise no challenge specific to the scientific validity
of the EPA-ORD data, but rely only on their generic challenge that RBC
data are inherently less reliable than brain data. No hearing is
warranted based on such evidence. See 49 FR 6672 (February 22, 1984)
(challenge to one of five related studies; in the absence of any
additional data bearing on the clinical study, the objection
constitutes nothing more than an allegation); 68 FR 46403 (August 5,
2003) (hearing denied because cited studies only contained equivocal
statements supporting objector's position).
Accordingly, the sum of their evidence is no more than mere
speculation that the effects of carbofuran exposure in the CNS will be
protective of effects in the PNS. This falls far short of the
``reliable data'' on the safety of infants and children needed to
justify the entire removal of the 10X children's safety factor and thus
cannot justify a hearing (40 CFR 178.21(b)(2)). See, e.g., 73 FR 42697
(July 23, 2008) (denying hearing where the only evidence submitted was
NRDC's claim that if the DDVP two-generation rat reproduction study had
been conducted pursuant to the 1998 guidelines it might have shown
endocrine effects at lower doses than the doses at which DDVP's
cholinesterase effects were seen on grounds that this was mere
speculation); 57 FR 6667 (February 27, 1992) (hearing denied to an
objector who challenged FDA's rejection of a study for only containing
partial histopathological data on the grounds that ``[s]peculation
regarding data that do not exist cannot serve as the basis for a
hearing'').
A detailed examination of Petitioners' evidence follows below.
(a) Testimony intended to show that brain is the appropriate
endpoint. Petitioners allege that the ``critical effect of concern due
to carbofuran is nervous system AChE. Brain is a direct measure of such
toxic effects, while RBC not linked to any biological function.'' On
this basis, they conclude that brain represents the most appropriate
endpoint for risk assessment.
Essentially this testimony fails to prove any dispute of material
fact. EPA relied on the carbofuran pup brain AChE inhibition data to
establish carbofuran's PoD. The Petitioners have not argued that PNS
effects are irrelevant. Indeed, their submissions make clear that
effects on the PNS are appropriate considerations in a risk assessment;
the only point they dispute is whether brain or RBC data best account
for those effects (Exhibits 4, 6).
Alternatively, if they intend to argue that RBC data entirely lacks
any scientific validity, this is contradicted in several places by
their other objections and their own submissions. As discussed above,
the commenters rely on the adult carbofuran RBC data to support their
claim that reliance on the pup brain data is adequately protective of
PNS effects. Moreover, they explicitly acknowledge that reliance on RBC
data is scientifically valid in the context of the human data (Obj at
13). Consequently, the submitted materials are insufficient to justify
the factual determinations urged, and therefore fail to support a
determination that an evidentiary hearing is warranted (40 CFR
178.32(b)(2)).
(b) Testimony purporting to show that reliance on brain data is
sufficiently protective of the PNS. The Petitioners raise several
arguments in this regard. First, they allege that, ``brain responds
rapidly to carbofuran, which readily passes blood/brain barrier'' (Obj
at 12-13). Petitioners' primary point, however, is that ``the extent of
brain inhibition by carbofuran more accurately compares with the extent
of PNS inhibition, and therefore brain data are adequately protective''
(Id.). In support of this claim, Petitioners cite to Exhibits 4 and 6,
containing a mixture of ``expert testimony'' and published studies.
None of the information contained in these exhibits is sufficient to
establish a reasonable possibility that this issue could be resolved in
their favor.
Petitioners' first claim simply reiterates points made in their
comments on the proposed rule. As explained in the final rule, EPA
agrees that the data show that the brain responds rapidly to
carbofuran, and that it readily passes the blood/brain barrier.
However, evidence regarding the speed with which the brain reacts
proves nothing with regard to the relative sensitivity of PNS tissues
(Ref. 85 at 46). Petitioners have presented nothing that challenges the
substance of EPA's response. Consequently, these claims do not present
a live controversy as to a material issue of disputed fact; both
parties agree on the facts at issue, which is that the brain responds
rapidly to carbofuran. Moreover, a simple repetition of comments made
on the proposal without more is insufficient to warrant a hearing. See,
e.g., 73 FR at 42698-42699 (July 23, 2008) (denying several NRDC
hearing requests because the objections were based on EPA's preliminary
DDVP risk assessment, rather than the revised risk assessment published
with the final order); 53 FR 53176 (December 30, 1988) (where FDA
responds to a comment in final rule, repetition of comment in
objections does not present a live controversy unless objector proffers
some evidence calling FDA's conclusion into question); 62 FR 64102,
64105 (December 3, 1997) (objector claimed that addition of ethoxyquin
invalidated studies; hearing denied because objector did ``not dispute
FDA's explanation in the final rule as to why addition of ethoxyquin
did not compromise the CIVO studies, and provided no information that
would have altered the agency's conclusion on this issue'').
Petitioners' second point--that brain AChE inhibition correlates
closely with PNS inhibition, and demonstrates that reliance on brain
data will be protective of the PNS--is a disputed material issue of
fact that could warrant a hearing, except that none of the evidence
submitted in support of this point presents a reasonable possibility
that the Petitioners could establish the points alleged. Consequently,
they have failed to demonstrate that a hearing is warranted on this
objection (40 CFR 178.32(b)(2)).
(c) Exhibit 4. This exhibit consists of a report by Kendall
Wallace, PhD, entitled ``Expert Report: Carbofuran FQPA Safety
Factor,'' along with published studies (Ref. 17, 51, 53, 54, 59, 61,
62, 72). The report argues that, ``it is my opinion that for
carbofuran, the evidence indicates that inhibition of brain AChE is an
appropriate surrogate for PNS AChE inhibition and that there is
reasonable certainty that a PoD for carbofuran based on brain AChE
inhibition is protective of any adverse CNS and PNS effects.'' The only
carbofuran evidence directly cited in support of this allegation is
data conducted on adult animals, using RBC AChE data, which they
elsewhere try to discount. This assumes that adults and pups are
similarly sensitive despite the carbofuran-specific evidence to the
contrary. No evidence is discussed or
[[Page 59636]]
submitted to support this assumption. This therefore constitutes a mere
allegation, which does not justify a hearing.
None of the published studies conducted with other chemicals cited
in the Report provide more than equivocal support for the points above;
in fact, in several instances, the study results support EPA rather
than the Petitioners.\12\ The studies contained in this exhibit fall
into two general categories. The first group of studies consists of a
subset of the chlorpyrifos literature--which is generally more relevant
to the subissue discussed in the next objection, arguing that RBC data
are not a good surrogate for the PNS--rather than demonstrating
affirmatively that brain is a protective surrogate for the PNS. The
second category of studies is one paper on physostigmine, a carbamate,
that is discussed in the body of the report. All but one of these
studies was conducted using adult rats.
---------------------------------------------------------------------------
\12\ It is interesting to note that, in Exhibit 4, the expert
actually faults EPA for comparing OP and NMC pesticides, saying
``Although OP pesticides inhibit AChE, they are completely different
from carbofuran and other N-methylcarbamates * * *:'' (Exhibit 4 at
4). Yet the Exhibit includes papers on effects of chlorpyrifos, an
OP, and these papers are not discussed in the text of the Exhibit.
---------------------------------------------------------------------------
Marable, et al. (Ref. 51) and Nostrandt et al. (Ref. 59) are two of
the chlorpyrifos studies Petitioners submitted as part of the comments
on the proposed rule, and they contain little evidence to demonstrate
that brain data correlate well with the PNS, and thus are generally
protective of the PNS. Marable et al. involved chronic exposures to
adult dogs; in addition to the fact that adult animals were used, and
therefore provide evidence of little relevance to the question at
issue, there are significant differences between the results of chronic
and acute exposures. As a result of the repeated exposures, blood,
brain and peripheral tissues were at steady state, which cannot occur
from an acute exposure, and therefore this study can provide no
information on the effects from acute exposures. Nostrandt et al.
actually reported that, following a single low dose of chlorpyrifos,
brain inhibition was less (not greater) than the inhibition obtained in
heart which is part of the PNS (although higher inhibition was not seen
in the diaphragm or retina, other parts of the PNS). At higher doses,
the inhibition in brain and peripheral tissues were more similar. Thus,
this study contradicts the Petitioners' claim that brain data will be
protective of all PNS effects. Petitioners offer no explanation of how
the resubmission of these studies addressed EPA's conclusion in the
final rule that the chlorpyrifos data failed to prove their claim.
Chen, et al. (Ref. 17), another study of chlorpyrifos, discussed
whether plasma or RBC AChE should be used to establish a regulatory
endpoint in humans and compared data from several animal studies, some
of which were conducted with adults and some with pups. This is the
only study in Exhibit 4 that contains data on pups. The results of one
of the studies reported in Chen, et al. shows that at the lowest doses,
inhibition was greater in the heart, which is part of the PNS, than in
the brain (56% and 41% respectively); note that these are the data in
adult rats reported in Nostrandt et al. (described above). Based on
data from a developmental study of chlorpyrifos by Hoberman (Ref. 37),
Chen et al. reported that the doses estimated to produce 50% inhibition
in heart and brain actually show that in 5-day old pups (both males and
females), the heart is 2-3 times more sensitive than brain. Thus, this
study contradicts Petitioners' claim that brain data will be protective
of PNS effects, since the PNS inhibition was greater than brain at the
lowest doses in both adults and pups. And in fact, it supports EPA's
concern that the absence of data at low doses is significant because
the effects at low doses can differ significantly from those at higher
doses. The data from Hoberman showed that at higher doses, ranging from
30-100 mg/kg, the levels of inhibition in the brain were higher than
the levels in the PNS (Ref. 37 at 16)--the exact opposite of what
occurred at the lowest doses.
The second group of studies consists of data on NMC chemicals.
McDaniel et al. (Ref. 53) and Padilla et al. (Ref. 62) were cited in
support of the claim that the difference in sensitivity between the
brain and RBC is generally less for NMC chemicals. These studies were
conducted with adult animals, and so do nothing to address the question
before the Agency with respect to pups. These studies merely confirm
the existing carbofuran data in adults, which shows that at the lowest
dose tested, brain and RBC are essentially the same.
Somani et al. (Ref. 72) is a study on another NMC chemical,
physostigmine, in adult animals, cited to support the claim that ``in
adult rats, brain AChE is somewhat more sensitive than RBC or
peripheral AChE to inhibition by acute doses of physostigmine.'' As an
initial matter, it is unclear that this study provides more than
equivocal support for their claim; the study authors claim only that
the brain ``appears'' to have the lowest values. However, even
conceding that this study shows that the CNS tissues in adult rats are
more sensitive to the effects of physostigmine than the PNS tissues,
the data in this study is of limited relevance to the issue at hand,
which is the effects in juveniles. Thus it is ultimately insufficient
to affirmatively support the Petitioners' claim.
In sum, based on the evidence contained in this exhibit, EPA
concludes that there is not a reasonable probability that the proffered
evidence would resolve the issue in Petitioners' favor, and that
consequently no hearing is warranted on this basis. First, all but one
of the studies discussed in this exhibit were conducted with adult
animals, rather than pups. As such, they provide evidence of little
relevance to the question of whether pups' PNS are more sensitive than
the CNS. In the absence of carbofuran PNS data, or pup RBC data, much
of this evidence is effectively mere speculation about whether adult
data will be predictive of pup responses, which cannot justify a
hearing (40 CFR 178.32(b)(1)).
(d) Exhibit 6. This exhibit consists of a report by Lucio Costa,
PhD, entitled, ``Expert Report: Carbofuran's FQPA Safety Factor and
Interspecies Uncertainty Factor,'' as well as published literature
studies conducted with chlorpyrifos and disulfoton, both OP pesticides,
and a single study with propoxur, an NMC pesticide (Refs. 71, 19, 20,
21, 61, 52, 41, 64, 16). According to Costa, these studies generally
show that there was similar or greater AChE inhibition in brain than in
the PNS tissues of heart, ileum, or the diaphragm, which Petitioners
claim proves that reliance on carbofuran pup brain AChE inhibition data
will necessarily be protective of all effects in the PNS (Exhibit 6 at
3). The exhibit also references a human incident study (Ref. 50) of
carbamate poisoning in early childhood and in adults, claiming that,
``Lifshitz * * * showed that signs of adverse effects in the CNS,
rather than PNS, prevailed in young children at the low dose levels
covered by the paper.''
EPA concludes that there is not a reasonable probability that the
evidence contained in this exhibit would resolve the issue in
Petitioners' favor. The results of these studies fail to demonstrate
the point for which Petitioners cite them--that brain AChE is always
equally or more sensitive than PNS AChE, and therefore exclusive
reliance on brain data can be assumed to be protective. Consequently,
the fact that Petitioners can identify examples of other chemicals,
whether OPs or NMCs, that sometimes affect the brain more severely than
the PNS does not prove
[[Page 59637]]
that this will be the case with carbofuran. Furthermore, in several of
the cited examples the Petitioners misinterpret the findings, which
actually support EPA's position.
As explained in EPA's final rule, Petitioners are relying on only a
subset of the chlorpyrifos data. The data, when examined in total, do
not support a conclusion that brain data will always be protective of
PNS effects (74 FR 23054-23055 (May 15, 2009)). But even relying solely
on the studies Petitioners reference in this exhibit, it is clear that
brain is not always inhibited to the same degree as peripheral tissues,
nor is it always protective of peripheral tissues. The data in Padilla
et al. (Ref. 61) are the only chlorpyrifos data that support a
conclusion that reliance on the CNS data will be protective of the PNS.
However, the Padilla study involved chronic dosing of rats via the
feed, and as such, cholinesterase measurements reflected steady-state
conditions. This study cannot provide information relevant to acute
exposure. None of the other chlorpyrifos studies referenced in this
exhibit support this conclusion. In Mattson et al. (Ref. 52), and
Hunter et al. (Ref. 41), following a single dose to pregnant dams,
heart and liver tissues were more inhibited than brain tissues.
Similarly, in Richardson and Chambers (Ref. 64), where repeated doses
were administered to pregnant dams, at both the low and high doses, the
lung tissue was more inhibited than the brain tissue in the one-day old
pups. In Carr et al. (Ref. 16), the results were more equivocal; in a
repeated dosing study using pups of varying ages, whether brain or
peripheral tissues were most inhibited depended on the age of the pups
and the dose. Nevertheless, Carr (2001) showed that brain inhibition
decreased as the age of the pups increased, even though inhibition in
the heart tissues did not. In other words, the submitted material only
supports a conclusion that brain is sometimes inhibited by chlorpyrifos
to the same degree as the peripheral tissues, and in reality, the
studies show that brain is often inhibited to a lesser extent than
peripheral tissues. This cannot support a conclusion that reliance
exclusively on brain data will necessarily be protective in the absence
of some additional carbofuran-specific evidence.
The results are similar for the disulfoton studies. Schwab et al.
(Ref. 71) shows that after both a single dose and repeated doses, the
brain and peripheral tissues were equally inhibited. However, these
results are contradicted by Costa et al. (Ref. 19) and Costa and Murphy
(1983), where the results varied depending on the dosing and the brain
area examined. In Costa and Murphy (Ref. 21), diaphragm tissues were
more inhibited than brain tissues after a single dose of disulfoton,
while after repeated doses, brain and diaphragm tissues were similarly
inhibited. Thus, the relative sensitivity between CNS and PNS changes
with repeated dosing, and these studies provide no information on RBC
inhibition with which to compare the other tissues.
Finally, the Lifshitz study does not support the claim for which it
was cited. The study presents no data on the dose levels associated
with the poisoning incidents, and in fact concludes that there was
``insufficient information to compare the doses ingested by [adults and
children].'' However, based on the symptomology reported (comas,
stupor, and severe hypotoxicity) it is likely that the doses were high,
not low, as the Report claims. Also, this study cannot be used to
discount PNS effects in children; a large percentage of the children
clearly showed PNS effects (myosis, diarrhea). In addition, because
this was a retrospective study of patients admitted to a hospital
intensive care unit, given the severity of some of the CNS symptoms,
such as comas, it is not unlikely that even if the subjects also showed
PNS symptoms, they were not reported. Finally, the study authors'
conclusion was that in children, the ``clinical presentation [of
carbamate poisoning] differs from adult poisoning manifestations''
(Ref. 50). Or in other words, that the effects in adults from exposure
to carbamates such as carbofuran are not necessarily predictive of the
effects in children. It is difficult to see how this study could be
fairly argued to support Petitioners' allegations.
In conclusion, the totality of the evidence in Exhibits 4 and 6
fail to support Petitioners' contention. As shown in Table 1 below, the
majority of the study results demonstrate that the PNS is frequently
more sensitive than the CNS. The remainder, taken in the light most
favorable to the Petitioners, provide merely equivocal support.
Table 1--Summary of Petitioners' Studies
----------------------------------------------------------------------------------------------------------------
Is CNS protective of
Study design Relative inhibition PNS?
----------------------------------------------------------------------------------------------------------------
Chlorpyrifos Studies
----------------------------------------------------------------------------------------------------------------
Padilla et al. 2005.................. Single dose, adults.... RBC > brain [ap] Yes (same sensitivity).
diaphragm.
Mattsson et al. 2000................. Single dose, pregnant RBC > heart > brain.... No.
dams.
Hunter et al. 1999................... Single dose, pregnant Liver > brain.......... No.
dams.
Blood not measured.....
Richardson and Chambers 2003......... Repeated doses to Low dose, lung > serum No.
pregnant dams, [ap] brain > heart.
measured pups at 1 day High dose, lung > brain
old (not direct dose). [ap] heart > serum.
Note, serum has only
[ap] 50% AChE, not
true measure of AChE.
Carr et al. 2001..................... Repeated doses to pups. PND6: brain [ap] Not always, depending
diaphragm > heart [ap] on age, dose, and
lung > skeletal muscle brain region.
[ap] serum.
PND10: heart [ap]
hindbrain [ap]
diaphragm [ap] lung >
skeletal muscle >
forebrain [ap] serum.
PND16: heart [ap] lung
> brain..
PND20: heart > lung >
brain..
PND25: brain > PNS.....
Brain inhibition
decreased with age,
heart did not.
[[Page 59638]]
Nostrandt et al. 1997 (also cited in Acute dose, adults..... RBC > heart > brain > No.
Chen et al. 1999). diaphragm.
Hoberman 1998 as cited in Chen et al. Repeated doses to RBC > heart > brain.... No.
1999. pregnant dams,
measured in pups at 5
days old (not direct
dose).
----------------------------------------------------------------------------------------------------------------
Disulfoton Studies
----------------------------------------------------------------------------------------------------------------
Schwab et al. 1981................... Single dose............ heart [ap] ileum [ap] Yes, similar
Repeated doses......... brain. sensitivity.
brain [ap] ileum >
heart.
No blood measured......
Costa et al. 1981.................... Single dose............ Brain > ileum.......... Not always, depends on
Repeated doses......... Forebrain > ileum > dosing paradigm and
hindbrain. brain region.
Brain [ap] ileum....... Not consistent within
same study.
Repeated doses......... No blood measured......
Costa and Murphy 1983................ Single dose............ Diaphragm > brain...... Not always, depends on
Repeated doses......... Brain [ap] diaphragm dosing paradigm.
[ap] plasma..
Note, plasma has only
[ap] 50% AChE, not
true measure of AChE.
----------------------------------------------------------------------------------------------------------------
Accordingly, Petitioners' proffer is facially insufficient because
there is no reasonable possibility that it can establish a necessary
element of Petitioners' objection--that there are ``reliable data''
that show it would be safe for infants and children to remove entirely
the 10X children's safety factor.
iii. Denial of objection. The objections do not address the
fundamental issue that EPA is required by the statute to resolve: Are
there `reliable' data to support reduction or removal of the statutory
10X for protection of infants and children? The statute compels that
EPA may only revise the 10X default safety factor if, ``on the basis of
reliable data'' EPA can conclude that the alternative safety factor
will be ``safe'' (21 U.S.C. 346a(b)(2)(C)). The statute also requires
EPA to account for the ``completeness of the toxicity data'' in making
this determination (Id). In this case, the Agency concluded that there
are sufficient data to reduce the 10X safety factor but there is
insufficient information to justify removing the factor entirely.
Similar to other AChE inhibiting pesticides, carbofuran can affect
both the central and peripheral nervous system. Because the relative
sensitivity of the central and peripheral nervous system varies among
pesticides and the children's safety factor should account for the most
sensitive toxicity endpoint, the Agency considers the availability of
data in both the central and peripheral nervous systems important in
its safety factor evaluation.
As shown in Figure 1, above, there are several datasets that
evaluate the effects of carbofuran on the central nervous system (e.g.,
brain AChE inhibition) in juvenile rats. There are no AChE data from
peripheral tissues. Lack of peripheral AChE data is typical of NMCs due
to the rapid reactivation of AChE. As a matter of science policy, the
Agency typically uses AChE data from blood, particularly RBCs, as a
surrogate measure for the peripheral nervous system (Refs. 76, 87). In
the case of carbofuran, RBC AChE data from two separate studies
submitted by FMC are considered unreliable and unusable in human health
risk assessment (Ref. 83). Data from EPA's ORD includes high quality
RBC AChE data, but only high doses were used in the ORD studies. Data
at the low end of the dose response curve are not available for
assessing the effects in juvenile rats, which are the doses relevant
for human health risk assessment. Thus, because reliable data are
available to assess affects on the CNS and some surrogate data are
available to assess the PNS, the Agency believes that the children's
safety factor can be reduced. However, this factor cannot be completely
removed since the available carbofuran data show that RBC AChE
inhibition in pups is more sensitive than brain AChE inhibition.
Given that (1) data from other AChE inhibiting pesticides show that
direct measures of peripheral nervous system (e.g., lung, heart, and
liver AChE) can be more sensitive than brain AChE inhibition; (2) a
surrogate measure of the peripheral nervous system (RBC AChE) is more
sensitive in juvenile rats to carbofuran; and (3) clinical signs
consistent with toxicity to the peripheral nervous system were seen at
very low doses, the Agency can not be confident that assessing risk
using brain AChE inhibition is protective of potential effects in the
peripheral nervous system for infants and children. For example, in the
first FMC-sponsored comparative ChE studies (Ref. 4) every pup at the
0.3 mg/kg dose group exhibited tremors. The range-finding portion of
the second FMC-sponsored comparative ChE study (Ref. 1) resulted in
tremors in rats exposed to 0.3 mg/kg carbofuran (\2/5\ males and \2/5\
females) within 15 minutes post-dosing.
Additional evidence for sensitivity of the PNS comes from
carbofuran data in pregnant rats that showed clinical signs that may be
indicative of peripheral toxicity. The California Department of
Pesticide Regulation (CDPR) has calculated a BMD10 and
BMDL10 of 0.04 and 0.03 mg/kg/day, respectively, for mouth
smacking and chewing in pregnant rats exposed to carbofuran. These
signs are early indicators of toxicity from some cholinesterase
inhibitors (Ref. 56). This is notable for two reasons. First,
cholinergic toxicity (e.g., tremors, miosis, salivation) may be
observed following inhibition of blood, but not brain, cholinesterase.
This was the case with fenamiphos (an OP pesticide), even up to
maximally tolerated doses (Ref. 53). Second, the BMDL10 from
the mouth smacking and chewing in pregnant rats is similar to that
being used by EPA for brain AChE in juveniles. The similarity of the
CDPR BMD in adults and EPA's BMD in juveniles is striking because all
of the available data show that pups are more sensitive than adults to
carbofuran toxicity. This therefore suggests that behavioral effects
and/or clinical signs may be occurring in juvenile animals at lower
doses, but which cannot be detected, in part due to the challenges
[[Page 59639]]
with assessing clinical signs in juvenile rats. As noted by the SAP,
this ``limitation reflects the limited range of toxic signs detectable
in very young pups (p. 54).'' This provides further support that the
lack of pup data at lower doses is significant, because the Agency
cannot fully evaluate the behavioral effects on juvenile animals.
Further support for the Agency's concern comes from other clinical
reports of the effects of carbamate poisoning in children. For example,
Lifshitz reported that all children presented with CNS symptoms (coma,
stupor), but CNS symptoms were observed in only 54% and 23% of children
as reported by Zweiner and Ginsburg (1988) and El-Naggar et al. 2009
(Refs. 91, 26). Peripheral muscarinic symptoms were the most commonly
reported (73% and 100%) signs of toxicity in these latter two reports.
These markedly different findings emphasize that conclusions cannot be
unequivocally drawn from only one study.
In addition, Petitioners' own data show that effects can differ
significantly between high and low doses. In Chen, for example, the
data from Hoberman showed that at the lowest doses the levels of
inhibition were higher in the PNS than in the brain, but at higher
doses, the levels were higher in the brain.
Thus, for a number of reasons, the Agency has concerns that
children's PNS may be more sensitive to the effects of carbofuran than
the CNS. This concern is the basis for retention of a portion of the
children's safety factor.
The carbofuran RBC data in adult animals does not resolve this
question. There can be substantial differences in response between pups
and adults, and, as noted, the data show clearly that pups are more
sensitive to the effects of carbofuran. It is not unusual for juvenile
rats, or indeed, for infants or young children, to be more sensitive to
chemical exposures as metabolic detoxification processes in the young
are still developing. Because pups are more sensitive than adult rats,
data from pups provide the most relevant information for evaluating
risk to infants and young children and are thus used to derive the PoD.
In addition, typically (and this is the case for carbofuran) young
children (ages 0-5) tend to be the most exposed age groups because they
tend to eat larger amounts of food per their body weight than do
teenagers or adults.
b. Objection/hearing request subissue: Reliance on RBC AChE
inhibition data as a surrogate for PNS effects. This objection also
challenges EPA's decision to retain some portion of the presumptive 10X
children's safety factor, rather than remove it entirely. As explained
above, EPA retained a portion of the presumptive 10X children's safety
factor because of the absence of sufficient data on PNS effects in
juveniles and the uncertainty created by the limited data relevant to
the PNS that showed greater sensitivity in juveniles. In the previous
subissue, Petitioners argued that in fact there is no uncertainty
created by the lack of low dose RBC data and the finding of sensitivity
in the RBC AChE data because brain AChE data is protective of PNS
effects. In this subissue, Petitioners attempt to buttress their first
argument by claiming that RBC AChE data are not an ``appropriate
surrogate'' for PNS effects, and should not have formed the basis for
retention of any portion of the children's safety factor.
Petitioners do not argue that RBC data are entirely irrelevant, but
rather that brain data are ``preferred.'' They raise several points in
support of this contention; first, that ``RBC AChE inhibition data are
only preferred for risk assessment purposes in two circumstances: (1)
Where the PoD is set using data from human studies where only RBC data
are available or (2) where data from the relevant target tissues are
unavailable.'' They allege that, despite the absence of carbofuran data
in the PNS tissues, brain is preferred in this case because the brain
is ``target tissue'' from the nervous system, and because brain data
are a ``better predictor'' of PNS effects than RBC. As further
evidentiary support, they cite to evidence from OP studies that RBC
AChE can ``in some cases'' be inhibited to a greater degree than either
PNS or brain AChE, and therefore reliance on RBC AChE data can
overstate potential PNS effects. They also argue that RBC AChE is more
variable and less reliably measured at low response levels, such as 10%
AChE inhibition. The evidence in Exhibits 4 and 6 is also proffered in
support of this objection.
i. Background. EPA's well-established policy when evaluating
cholinesterase-inhibiting compounds is to rely on data in the target
tissue where it is available (Ref. 76). As noted in the preceding
section, measures of AChE inhibition in the PNS are rarely collected
for NMC pesticides. And in fact, there are no carbofuran data measuring
effects in PNS tissues. But in the absence of target tissue data, as a
matter of science policy, EPA typically uses RBC AChE inhibition data
as an indicator of possible effects on AChE in the PNS for number of
reasons. (Ref. 76 at 32). Although RBC AChE inhibition is not adverse
in itself, it is a surrogate for inhibition in peripheral tissues. As
such, RBC AChE inhibition provides an indirect indication of adverse
effects on the nervous system (Id.).
Petitioners raised many of the same issues raised in the objections
in their comments on the proposed rule. For example, they argued that,
``as a matter of science policy, brain AChE inhibition is the preferred
endpoint over RBC AChE inhibition.'' They also argued that no
physiological function has been demonstrated for RBC, and RBC AChE
inhibition is not itself an adverse effect.
In the final rule, EPA responded to each of their comments, but
concluded that no information had been submitted to justify altering
the Agency's general policy that reliance on RBC is appropriate as a
surrogate for PNS effects in the absence of direct measurements in PNS
tissues.
ii. Denial of hearing request. This subissue does not raise a
dispute of material fact. There is no dispute regarding many of the
facts raised in this objection: When data in the target tissue are
available, it is preferred over a surrogate. RBC AChE can be more
variable and less reliably measured at low response levels than brain
AChE. RBC AChE inhibition can, in some cases, be more extensive than
PNS AChE inhibition. Equally, there is no dispute that no physiological
function has been demonstrated for RBC, and RBC AChE inhibition is not
itself an adverse effect. All of these points are explicitly recognized
in EPA's Cholinesterase policy and in the tolerance revocation
rulemaking record, and relate purely to the ease or wisdom of relying
on these measures rather than others, as opposed to the scientific
invalidity of such data. The only point on which there is a dispute is,
given that there is no data in the target tissues of the PNS, which
data--brain or RBC--is ``preferred.'' The Petitioners expressly
acknowledge this to be the issue: ``There are other surrogate measures
of PNS AChE that could have been selected by OPP, such as brain AChE''
(Exhibit 4 at 5). This is clearly a question of scientific policy,
since both EPA and the Petitioners agree on the scientific validity and
relevance of RBC AChE inhibition data. As they expressly acknowledged
in their comments, the choice of which surrogate to use is a matter of
``science policy'' (Ref. 18). Indeed, Petitioners explicitly concede
the propriety of relying on RBC data ``where data from the relevant
target tissues are unavailable, or when relying on human data, where
RBC AChE inhibition data are the only data available (Obj at 13).
Hearings are not
[[Page 59640]]
appropriate for debating questions of policy (40 CFR 178.32(b)(1)).
Nor does the proffered evidence present any other issue that would
warrant a hearing. The evidence submitted in Exhibits 4 and 6 on this
point only relates to the question of whether brain data can sometimes
correspond more closely with PNS effects than RBC AChE data, rather
than the question of whether the RBC data are scientifically invalid.
Or in other words, the submitted materials relate only to the point
that reliance on RBC data is unnecessarily conservative, because
sometimes it overestimates the potential PNS effects, rather than to
the factual question of whether RBC data bears no relation whatsoever
to PNS effects. Unless Petitioners can show that RBC AChE is not
related to CNS effects generally or specifically for carbofuran, or
that brain AChE is protective of CNS effects generally or specifically
for carbofuran, then the mere fact that RBC AChE may be a conservative,
or even very conservative, indicator of PNS effects is simply
immaterial to the question of whether there are ``reliable data'' to
justify removing the presumptive 10X children's safety factor in the
absence of sufficient RBC AChE data. As shown in the discussion of
subissue 1, the Petitioners' evidence does not demonstrate that
reliance on juvenile brain data as a surrogate for effects in the
juvenile PNS will guarantee that the levels chosen on that basis will
be predictive of all PNS effects from carbofuran, because the PNS
effects occur only at the same or higher doses than those that produce
effects on the brain AChE--i.e., that the brain data ``bound'' all
potential PNS effects. Nor, as discussed below, does any of
Petitioners' evidence support a conclusion that RBC AChE is unrelated
to PNS effects.
Indeed, much of the evidence in the Exhibit 4 and 6 Reports is
ultimately an irrelevance, and thus fails to present a material factual
dispute. Instead of focusing the stated objection--RBC AChE is
inappropriate marker for CNS effects--the Reports attempt to link EPA's
children's safety factor decision to findings concerning chlorpyrifos
(Exhibit 4 at 4). In fact, a fair portion of the Report in Exhibit 6 is
dedicated to a rebuttal of EPA's conclusion that the majority of the
more recent and more relevant chlorpyrifos evidence did not support
Petitioners' contention. EPA, however, has been clear throughout the
rulemaking that the basis for retention of a children's safety factor
has been the absence of carbofuran data to determine the levels of
exposure that will be protective of children's PNS, in the context of a
statutory provision that expressly requires EPA to account for missing
data. EPA's point in discussing the chlorpyrifos data--which
Petitioners initially raised as relevant--was simply that it showed
that because peripheral tissues can be more sensitive than central
nervous system tissues, the absence of data addressing carbofuran's
effects on the PNS is highly relevant. Whatever the chlorpyrifos data
show cannot resolve the extent of carbofuran's risks. As the
Petitioners' experts themselves point out, ``Even conceding that [EPA's
conclusion in the final rule that peripheral tissues are often shown to
be more sensitive than brain tissue following exposure to chlorpyrifos]
may be true, it is still unclear how this would be relevant to
carbofuran * * *'' (Exhibit 6 at 3). Accordingly, this evidentiary
submission fails to demonstrate that a dispute exists on a question of
material fact.
Finally, their submission provides an inadequate basis on which to
grant a hearing; because evidence is not proffered on critical points,
the objection ultimately rests on allegation, speculation, and general
denials (40 CFR 178.32(b)(2)). As discussed in preceding section, the
majority of the evidence comes from adult data, which are of limited
relevance. Further, and more significantly, the evidence fails to
demonstrate that brain data always--or even more frequently than not--
correlates more closely with PNS effects than RBC AChE data. Instead,
the proffered evidence only demonstrates that whether brain or RBC data
correlate better with actual PNS effects can vary depending on the
chemical. This, therefore, cannot resolve the question as to whether,
in the case of carbofuran, brain AChE data will necessarily correspond
more closely with the PNS. Finally, as also discussed in the preceding
section, Petitioners' argument is internally inconsistent, because they
rely on carbofuran adult RBC AChE data to support their argument that
exclusive reliance on the brain data will be protective of potential
PNS effects in pups. No hearing is appropriate where the proffered
evidence fails to prove the points for which it is offered, or offers
merely equivocal support (See, 73 FR 42705 (July 23, 2008) (hearing
denied because published articles focus on an issue not applicable to
the facts of the case at hand); 68 FR 46405-46406 (August 5, 2003) (a
hearing was denied because the cited studies only contained equivocal
statements)).
A detailed examination of Petitioners' evidence follows below:
(a) Exhibit 4. As discussed in the previous objection, this exhibit
consists of a report, along with published studies. The Report
criticizes EPA for assuming that RBC AChE inhibition provides ``a
stronger and more quantitative concordance with the sensitivity of AChE
of the PNS to inhibition by carbofuran,'' on the ground that EPA failed
to cite to evidence to support this inference (Exhibit 4 at 5). In the
absence of such evidence, the report concludes that, ``one cannot
discount the plausibility that brain AChE may be a more quantitative
and representative surrogate measure of PNS sensitivity'' (Id). To
support this allegation, the report argues that the cited NMC data show
that the difference in sensitivity between brain and RBC shown with NMC
chemicals is less than the differences seen with OP chemicals, citing
studies by Padilla et al. (Ref. 62) and McDaniel et al. (Ref. 54). In
this regard, the Report actually misquotes McDaniel et al. The Report
claims that the paper concluded that there was a stronger correlation
between brain AChE inhibition and motor activity. The study actually
concluded that there was little difference between brain AChE
inhibition and RBC AChE inhibitions (``higher correlation for brain and
motor activity compared to RBC were not significantly different.'')
(Ref. 54). In any event, the Report's equivocal conclusion that ``one
cannot discount the plausibility'' that brain AChE might be the most
representative measure of PNS effect is, on its face, insufficient
grounds to overcome the statutory presumption for retention of the
additional 10X children's safety factor in the face of the evidence of
children's additional sensitivity to carbofuran, and the lack of
carbofuran data in PNS tissues or in a surrogate for such tissues, RBC
AChE.
Chen et al. (Ref. 17), which was discussed at length in the earlier
objection, evaluated whether plasma or RBC AChE should be used to
establish a regulatory endpoint; it did not evaluate whether brain AChE
would be an appropriate surrogate for PNS effects. It is true that the
authors conclude that ``[i]nhibition of RBC AChE activity is
consistently exhibited at lower dosages of chlorpyrifos than those
required to result in clinical symptoms of OP toxicity, or alterations
in cognitive functional responses.'' However, since the study authors
ultimately concluded that, ``inhibition of RBC AChE activity is an
appropriate surrogate for measurement of chlorpyrifos exposure and
provides a conservative endpoint for establishing appropriate margins
of
[[Page 59641]]
safety for both adults and infants,'' it is difficult to see how this
could be argued to provide unequivocal support for Petitioners'
objections.
Exhibit 6. This exhibit consists of a report by Lucio Costa, PhD,
entitled, ``Expert Report: Carbofuran's FQPA Safety Factor and
Interspecies Uncertainty Factor,'' as well as published literature
studies. The report discussed the results of several published studies
that they claim demonstrate that ``where available, brain AChE
inhibition data provide a superior surrogate'' to RBC data because ``in
some cases RBC AChE may overestimate PNS AChE inhibition, while in
other cases * * * RBC AChE inhibition may underestimate actual AChE
inhibition in the PNS.'' In support of this allegation, the report
references data from several studies conducted with chlorpyrifos and
disulfoton, both OP pesticides, and a single study with propoxur, an
NMC pesticide (Refs. 16, 19, 20, 21, 41, 52, 61, 64, and 71). According
to the Report, these studies generally show that there was similar or
greater AChE inhibition in brain than in the PNS tissues of heart,
ileum, or the diaphragm, which Petitioners claim proves that reliance
on carbofuran pup brain AChE inhibition data is more predictive of all
effects in the PNS. The exhibit also references a human incident study
(Ref. 50) of carbamate poisoning in early childhood and in adults,
claiming that, ``Lifshitz * * * showed that signs of adverse effects in
the CNS, rather than PNS, prevailed in young children at the low dose
levels covered by the paper.''
In its denial of the hearing request on the previous issue, EPA
examined the results of the studies in this exhibit at length, and
demonstrated that the results of the studies failed to support a
conclusion that brain data correlate more closely to PNS effects than
RBC data. Indeed, in most of these studies, brain AChE inhibition
poorly reflected the AChE inhibition in PNS tissues. For example, the
Carr et al. study results, reproduced in Table 1 of Exhibit 6, showed
that for PND 10, 16, and 20 rat pups, the heart tissue had the greatest
levels of inhibition, and that PND 16 and 20 rat pups had greater
levels of inhibition in lung tissue than in the brain (Ref. 16 at 3).
Further, since the study was conducted with serum, which contains no
RBC, it is unclear how this study could prove that brain data are a
better indicator of PNS effects than RBC data.
The remainder of the report consists of criticisms of EPA's
conclusions, and contentions that EPA was inconsistent, without
citation to biological evidence to support these claims. For example,
the Report addresses EPA's rejection of the Bretaud study in goldfish
on the grounds that the ``distribution of carbofuran across fish and
mammalian tissues may be quite different,'' by criticizing EPA for
failing to provide ``evidence or a citation to support this point''
(Exhibit 6 at 1). But they cite to nothing demonstrating the similarity
of fish and mammalian tissues or otherwise supporting their proposed
extrapolation across taxa; at this stage of the administrative process
the obligation is on the Petitioners to come forward with evidence to
call EPA's conclusions into question. See, 73 FR 42683, 42706, July 23,
2008 (``NRDC does no more than state `we are aware of no statistical
test' which would support EPA's use of the Gledhill data. As EPA's
regulations make clear, a mere `denial' of an EPA position is not
enough to satisfy the standard for granting a hearing.''); 53 FR 53176,
53199, December 10, 1982 (``Rather than presenting evidence, [the
objector] asserts that FDA did not adequately justify its conclusions.
Such an assertion will not justify a hearing.''). The report also
attempts to dismiss EPA's conclusions by complaining that EPA's
assessment fails to include ``any analysis of the relationship between
RBC AChE and PNS AChE.'' This also, cannot justify a hearing. As has
been previously noted, FMC, who bears the statutory burden for
producing such data, has failed to provide data in the PNS that would
allow EPA to make the suggested comparison (See, 73 FR 42683, 42699,
July 23, 2008 (hearing denied where NRDC made no evidentiary proffer
supporting its claim that each of the factors cited in EPA's risk
assessment ``poses a serious risk of understating the risks''); 70 FR
21619, April 27, 2005 (objector questioned exposure assessment and
studies relied on for assessment; hearing denied because no information
presented); 72 FR 39557, 39560, July 19, 2007 (``Although Public
Citizen alleged that the studies that FDA evaluated do not support the
safety of x-rays of 10 MeV or lower used for inspection of cargo
containers that may contain food, Public Citizen did not present any
evidence that would have led to a different conclusion concerning the
safety of the subject additive.'').
iii. Denial of Objection. EPA's well-established policy when
evaluating blood cholinesterase inhibition is to use RBC AChE data as
an indicator of possible effects on AChE in the PNS; EPA adopted this
policy for a number of reasons (Ref. 76 at 32). EPA's reasoning here is
straightforward. As a biomarker of exposure, blood AChE inhibition can
be correlated with the extent of exposure. There is often a direct
relationship between a greater magnitude of exposure and an increase in
incidence and severity of clinical signs and symptoms as well as blood
AChE inhibition. In other words, the greater the exposure, the greater
the amount of AChE inhibition that will be present in the blood and the
greater the potential for an adverse effect to occur. RBC measures of
AChE inhibition also provide: (1) Pharmacokinetic evidence of
absorption of the pesticide and/or its active metabolite(s) into the
bloodstream and systemic circulation; and (2) pharmacodynamic evidence
of binding to AChE, the neural form of the target enzyme. Because the
interaction with AChE is widely accepted as a key event of the
mechanism of toxicity for anticholinesterase pesticides, inhibition of
this AChE in the blood creates the presumption that a chemical also is
causing inhibition of neural AChE. Chemicals are absorbed into the
blood and transported to the PNS. Pharmacokinetically, the blood
compartment and the PNS are ``outside of'' the central nervous system,
i.e., separated from the CNS by the blood-brain barrier. Thus, RBC
measures of AChE activity are viewed as a better surrogate for the
effects on AChE in the peripheral nervous system than are enzyme
changes in the CNS. Because data on AChE inhibition in the PNS have
rarely been gathered in animals, blood AChE inhibition measures are
generally the only information available to assess the potential of
chemicals to inhibit AChE in the peripheral nervous system.
Finally, based on the record, FMC seemingly intended in the past
for RBC AChE to be used as a surrogate for peripheral AChE inhibition.
In 2005, FMC submitted a time course study with plasma and RBC AChE
inhibition following acute exposure to carbofuran in adult rats. The
title of this study is ``The toxicokinetics of peripheral
cholinesterase inhibition from orally administered carbofuran in adult
male and female CD rats (Ref. 5).'' Although this study is entitled
``peripheral cholinesterase inhibition,'' there are no actual measures
of peripheral toxicity (e.g., liver, lung, heart). Instead, RBC and
plasma ChEs are the only measures included. That report states that
``carbofuran reversibly inhibits cholinesterase activity by binding to
acetycholinesterase in red blood cells * * * Carbamylation of
cholinesterase after the association of carbofuran leads
[[Page 59642]]
to an accumulation of acetylcholine and inhibition of nerve function at
the neuronal and neuromuscular synapse.'' Based on this statement, FMC
assumed at the time of conducting and submitting this study that
measures of RBC AChE were relevant for predicting neurotoxicity and for
use in risk assessment. For all of these reasons, the Petitioners'
objection is denied.
c. Objection/hearing request subissue: ``Lip-smacking'' as CNS
effect. Petitioners object that EPA's evidence of ``lip smacking'' in a
carbofuran adult developmental rat study does not support concern for
potential PNS effects because lip smacking is more properly correlated
to CNS, rather than PNS inhibition. In support, the Petitioners proffer
testimony that relies on four published studies, none of which was
conducted with carbofuran. The papers describe pharmacological and
physiological analyses of the bases of ``purposeless chewing
movements'', ``chewing jaw movements'', ``chewing motions and tongue
protrusions'', and ``tongue protrusion and gaping'' seen in rats dosed
with either cholinergic or dopaminergic drugs.
i. Background. In the proposed rule, in addition to the data in
pups showing frank PNS effects (tremors), EPA discussed the results of
another carbofuran study that appeared to be a possible consequence of
PNS inhibition, to provide further explanation of the basis for EPA's
concern that carbofuran could cause adverse PNS effects. The proposed
rule stated that ``[t]here is indication in a toxicity study where
pregnant rats were exposed to carbofuran that effects on the PNS are of
concern; specifically, chewing motions or mouth smacking was observed
in a clear dose-response pattern immediately following dosing each
day'' (73 FR 44873, July 31, 2008). EPA explained that the California
Department of Pesticide Regulation calculated a BMD05 and
BMDL05 of 0.02 and 0.01 mg/kg/day, and established the acute
PoD based on this study. The Agency also explained that ``[t]hese BMD
estimates are notable as they are close to the values EPA has
calculated for brain AChE inhibition and being used as the PoD for
extrapolating risk to children'' (73 FR 44873, July 31, 2008). The
similarities of the BMDs in adult and juvenile rats suggests that
toxicity may be occurring in juvenile animals which cannot be detected
due to the challenges with assessing clinical signs in juvenile rats.
The Petitioners did not raise the allegation contained in their
objections as part of the Petitioners' comments. The context in which
``lip smacking'' was addressed was a sentence that states, ``One issue
raised at the FIFRA SAP meeting was whether `lip smacking' observed in
the adult females in the developmental toxicity study were the result
of PNS or CNS AChE inhibition'' (Ref. 18 at 82). In a footnote to this
allegation, the Petitioners stated ``Moreover, it is impossible to tell
from the study data whether this ``lip smacking'' was a PNS or a CNS
effect.'' (Ref. 18 at 82). The Petitioners' comments focused instead on
the contention that the study was irrelevant because the dose levels in
the study were higher than the dose levels at which EPA was regulating
for AChE inhibition (Ref. 18 at 82).
EPA did not respond to the Petitioners' description of the
discussion at the SAP, since it correctly characterized the discussion.
However EPA responded fully to the Petitioners' comment regarding the
dose levels in the final rule and response to comments.
ii. Denial of hearing request. There can be no legitimate argument
that this comment raised the issue in sufficient detail to allow
Petitioners to object that ``lip smacking'' is more properly correlated
with CNS inhibition, and to supplement the objection with the published
literature studies they cite here. See, e.g., Forest Guardians v. US
Forest Service, 495 F.3d 1162, 1170-1172 (10th Cir. 2007) (Claim held
waived where comments ``failed to present its claims in sufficient
detail to allow the agency to rectify the alleged violation'');
National Association of Manufacturers v. US DOI, 134 F.3d 1095, 1111
(DC Cir. 1998) (``We decline to find that scattered references to the
services concept in a voluminous record addressing myriad complex
technical and policy matters suffices to provide an agency like DOI
with a `fair opportunity' to pass on the issue.'') For the reasons
discussed in Unit VI.C, EPA considers the objection and evidence
untimely, and therefore waived. As such, this objection does not
warrant a hearing.
But in any event, this issue is not material. EPA's decision to
retain a 4X children's safety factor did not rest exclusively, or even
significantly--on the effects observed in this developmental study.
Rather, EPA retained the children's safety factor based on the lack of
data in the PNS and/or a surrogate at the low end of the response
curve, and the fact that the available pup RBC data at higher doses
affirmatively indicate that the PNS appears to be significantly more
sensitive than the CNS (73 FR 44871-44872; 74 FR 23073-23075). Indeed,
it is clear from both the proposed and final rules that the results of
this study merely supplemented the Agency's bases for concern (73 FR
44871-44872; 74 FR 23073-23075). The Petitioners' complaint that the
effects occurred at dose levels three times higher than PoD and
therefore do not quantitatively support the 4X children's safety factor
is equally immaterial. The record is clear that EPA relied on
comparisons between the BMD50 estimated for pup brain and
RBC AChE inhibition to derive the 4X (73 FR 44871-44872; 74 FR 23073-
23075). A hearing can only be based on a genuine issue of disputed
fact. Where a party's factual allegations are contradicted by the
record, there is no genuine dispute (40 CFR 178.32(b)(1)) (See, 73 FR
42683, 42701 July 23, 2008; 57 FR 6667, 6672, February 27, 1992) (``A
hearing must be based on reliable evidence, not on mere allegations or
on information that is inaccurate and contradicted by the record.'').
iii. Denial of objection. The carbofuran developmental study does
not definitively resolve whether the effects described were the product
of PNS or CNS AChE inhibition; because only RBC AChE inhibition data
were collected it is not possible to determine the degree of CNS
inhibition. However, as the Petitioners acknowledge, chewing or oral
fasciculations, which are the movements EPA described at the SAP
meeting and in the proposed and final rules, have often been reported
as an early sign of toxicity produced by carbamates and OPs in rats
(Exhibit 5 at 2). Petitioners also acknowledge that ``oral
fasciculations'' are indeed a peripheral neuromotor response (Id.)
(``some of the toxicity is peripherally mediated or an effect on the
PNS (for example, muscle fasiculations and tremors are due to
inhibition of AChE at the motor endplate of the muscle)'').
Nevertheless, Petitioners attempt to confuse the issue by providing
several different descriptions of oral movements, from lip-smacking to
mouth smacking to mouth movements to chewing movements, and claiming
that it is clear that these are all CNS effects. As an initial matter,
it is unclear whether all of the study authors in Petitioners' cited
literature are referring to the same phenomenon. It is therefore
unclear whether the oral movements from the carbofuran developmental
study (which EPA described as ``lip-smacking'' and ``fasiculations'')
are the same responses described as ``tongue protrusion,'' ``gaping,''
``yawning,'' and ``chewing movements'' in the pharmacology papers
Petitioners reference. It is not unlikely that all of
[[Page 59643]]
the different papers refer to somewhat different actions; Rupniak et
al. (Ref. 68) were able to produce ``chewing jaw movements'' by chronic
treatment with haloperidol, a dopaminergic receptor antagonist, which
suggests that the movements studied in that paper are not purely
cholinergic. The fact that anticholinergics could block the
haloperidol-induced dopaminergic movements shows that this is not a
straightforward physiological response dealing only with the
cholinergic system. For the same reason, this calls into question the
contention that the effects are exclusively CNS-related.
Similarly, the claim that the ``the masticatory response'' is
clearly a CNS effect is equally misleading and inaccurate. The report
in Exhbit 5 claims that ``[t]he masticatory response is considered a
preliminary index of convulsive activity and convulsions have been
demonstrated to be caused by changes in brain chemistry.'' None of the
papers the Petitioners cited describe this ``masticatory response'' in
that way. Instead, those papers all state that this response is seen at
relatively low doses of these anticholinesterases. By way of contrast,
convulsions are seen at high doses. The Exhibit also implies that the
``masticatory'' response and convulsions are a continuum of the same
phenomemon; however EPA is aware of no scientific support for this
claim, and Petitioners have provided none.
Petitioners' objection on this issue is therefore denied.
The Exhibit also implies that the ``masticatory'' response and
convulsions are a continuum of the same phenomemon; however EPA is
aware of no scientific support for this claim, and Petitioners have
provided none.
d. Objection/hearing request subissue: EPA's analysis does not rely
on Good Laboratory Practice (GLP)-compliant studies. Petitioners object
that EPA's reliance on the ORD data is problematic because the data
were not conducted in accordance with EPA's GLP regulations at 40 CFR
part 160.
i. Background. The only data available on the effects of carbofuran
on the pup PNS are RBC AChE inhibition data from two studies conducted
by EPA-ORD. These data unequivocally show that pup RBC AChE is more
sensitive than pup brain AChE. EPA also used these data in its
calculations supporting the 4X children's safety factor. In their
comments on the proposed rule, Petitioners alleged that, ``the Moser
study may not meet minimum criteria for scientific acceptability.''
They based this on a claim that critical data were unavailable for this
study, including: A complete protocol, analysis of dosing solutions,
clinical observations, standardization of brain and RBC AChE results in
terms of amount per unit of protein, and quality assurance records of
inspections for the carbofuran portion of the study. However, no more
specific explanation was provided as how this purportedly missing data
rendered the data scientifically deficient. EPA responded in full to
these allegations in the final rule and response to comments document.
EPA's regulations at 40 CFR part 160 establish a set of principles
that provides a framework within which laboratory studies are planned,
performed, monitored, recorded, reported, and archived. GLP helps
assure EPA that the data submitted are a true reflection of the results
obtained during the study and can therefore be relied upon when making
risk/safety assessments. The regulations are applicable only to studies
that support, or are intended to support applications for ``research or
marketing permits'' for pesticides regulated under FIFRA (40 CFR
160.1(a)).
ii. Denial of hearing request. On several grounds, a hearing on
this subissue is not warranted. First, this objection fails to identify
a dispute of material fact. There is no dispute that the EPA-ORD
studies were not conducted in strict accordance with EPA's GLP
regulations. Nor have Petitioners identified a substantive flaw in
those studies that they believe resulted from the lack of compliance
with the regulations, or otherwise challenged the scientific validity
of those studies. Thus, the only issue presented is whether EPA should
rely on otherwise scientifically valid studies that were not conducted
in accordance with its GLP regulations. This is clearly a legal or
policy issue. Hearings are not appropriate on such issues; issues of
fact, not of law or policy are required to justify a hearing (40 CFR
178.32(b)(1)).
A further defect is that Petitioners have submitted no evidence on
this point. In fact, this claim consists of nothing more than the bare
statement that EPA's analysis does not rely on GLP-compliant studies. A
hearing will not be granted on ``mere allegations'' or ``general
contentions'' (40 CFR 178.32(b)(2)). To the extent the Petitioners are
relying on the information submitted as part of their comments on the
proposed rule, this does not cure the defect, since no substantiating
information or other evidence was presented in support of their
comments. Nor can simple reiteration of a comment made on the proposed
rule justify a hearing. EPA responded to these comments in the final
rule, and by ignoring the EPA's final rule on this subissue,
Petitioners have failed to lodge a relevant objection. Both EPA and FDA
precedent make clear that when the agency substantively responds to
comments on the proposal, the commenter may only keep that issue alive
in its objections by addressing the agency's substantive response. See,
e.g., 73 FR 42701 (denying hearing because NRDC merely repeated its
assertion that the study was not representative from its petition,
rather than objecting to the basis EPA asserted in its petition denial
for concluding that the study was representative).
Indeed, this entire objection is not material. The EPA-ORD data are
the only valid pup RBC data using carbofuran; in the absence of these
data, EPA would have no data that would provide relevant information on
carbofuran's effects on children's PNS. Under such circumstances, EPA
would be required to retain the statutory default 10X, because there
would be no ``reliable data'' on which to base any other factor.
iii. Denial of objection. The mere fact that a study is not
conducted in accordance with EPA's GLP regulations does not mean that
the study is scientifically invalid, or that EPA is prohibited from
considering the study. The GLP regulations do not apply to EPA-ORD
generated data, but rather to studies conducted to ``support
applications for research or marketing permits for pesticide products''
(40 CFR 160.1(a)). Moreover, the regulations establish general
practices; they do not identify the only good laboratory practices that
will result in scientifically valid data. Other laboratory protocols,
such as that used by EPA-ORD are equally valid. In recognition of this
fact the regulations do not prohibit EPA from considering studies that
were not conducted in accordance with EPA's GLP regulations, but merely
provide that EPA may refuse to consider such studies to be ``reliable''
(40 CFR 160.17(a)).
Nor does compliance with EPA's GLP regulations guarantee the
validity of the study's results. The RBC data from FMC's carbofuran CCA
studies, which were conducted in accordance with EPA's GLP regulations,
were unanimously determined to be scientifically invalid by the FIFRA
SAP (Ref. 36).
Any claim that the conduct of the EPA-ORD studies raised questions
as to their scientific validity is equally baseless. EPA's ORD data
were reviewed by the FIFRA SAP, which concluded that, ``EPA-ORD has
provided excellent
[[Page 59644]]
data regarding RBC AChE inhibition by carbofuran'' (Ref. 36 at 55).
As EPA explained in response to the Petitioners' comments, all of
the information the Petitioners claimed was missing had been previously
made publically available as part of the SAP review of the carbofuran
NOIC, and was provided again in response to FMC's FOIA request. A
complete study protocol, as well as a report of the quality assurance
(QA), technical, and data reviews of the study, were available, which
demonstrated that the procedures and documentation are in accordance
with the National Health and Environmental Effects Laboratory (NHEERL)/
ORD Quality Assurance Management Plan. Concerning standardization of
brain and RBC AChE in terms of protein concentration, the Agency notes
that this analysis has not been performed or provided in all the
studies on the record, including those sponsored by FMC. However, in
the Moser study (Ref. 56), the AChE activity was standardized in terms
of tissue weight per ml, so the amount of protein was consistent across
samples, which is an acceptable and widely used practice. Further,
abnormal (or ``clinical'') observations were recorded when they
occurred, although the animals could not be watched while they were in
the motor activity chambers. Finally, the registrant is correct that
the dosing solutions for the comparative ChE study were not analyzed,
but ORD performed this analysis for the adult studies in McDaniel et
al. (Ref. 54), and the preparation and stability of the carbofuran
samples were confirmed therein. For these reasons, this objection is
denied.
e. Objection/hearing request subissue: Consistency of EPA's
approach to deriving the carbofuran children's safety factor--i.
Background. The Petitioners argue that EPA's approach to deriving
carbofuran's children's safety factor is inconsistent with that
Agency's approach in deriving the safety factors for other NMC
chemicals. Specifically, they point to carbaryl, which had a safety
factor of 1X.
Petitioners raised this issue in their comments on the proposed
rule. In the final rule, EPA explained at length, the basis for its
conclusion that the available data using carbaryl, provided by the
carbaryl registrant, supported a finding that a 1X children's safety
factor would be ``safe'' (74 FR 23058 and Ref. 85). EPA explained that
the different safety factors established for carbaryl and carbofuran
resulted from differences in the chemicals themselves, as reflected by
the available data (Id).
ii. Denial of hearing request. A hearing is not appropriate on this
objection because it raises a legal or policy claim, rather than a
dispute as to a material issue of fact. The claim that EPA acted
inconsistently in assessing different pesticide chemicals is purely a
legal issue. There is no factual dispute that EPA established a
children's safety factor of 1X for carbaryl, and a safety factor of 4X
for carbofuran. The only dispute concerns whether EPA's basis for
distinguishing between the two is reasonable, and this is a legal
claim, on which a hearing is not appropriate (40 CFR 178.32(b)(1)).
In addition, the Petitioners make no claim other than to reiterate
the allegation made in their comments on the proposed rule, that EPA's
assessment of carbofuran is inconsistent with its assessment of
carbaryl. Consequently, Petitioners' objection on this subissue is
irrelevant, and therefore immaterial, with regard to EPA's final
tolerance revocation regulation because Petitioners ignored EPA's
extensive analysis of this issue in the final rule and refiled their
comments on the proposal as if EPA's determination in the final rule
did not exist. By ignoring the EPA's final rule on this subissue,
Petitioners have failed to lodge a relevant objection. Nor have they
proffered any evidence in support of this claim. When EPA responds to a
comment in the final rule, mere reiteration of the comment in
objections does not present a live controversy unless the objector
proffers some evidence calling EPA's objection into question (See,
e.g., 73 FR 42700-42701).
iii. Denial of objection. Carbaryl was evaluated no differently
than carbofuran. The different children's safety factors applied to
each chemical reflects the differences in the chemicals themselves, as
reflected by the data.
It is typical EPA practice to use the central estimate on the BMD
as an appropriate measure for comparing chemical potency and the lower
limit on the central estimate (i.e., BMDL) as an appropriate measure
for extrapolating risk. In the case of carbaryl, the Petitioners
inappropriately focused on the BMDL10, instead of the
BMD10. The more appropriate comparison is between the
BMD10; the carbaryl brain BMD10 is 1.46 mg/kg
compared with the RBC BMD10 of 1.11 mg/kg. As such, the
brain to RBC ratio is 1.3X. Therefore, for carbaryl, the brain and RBC
AChE data are similarly sensitive. When the tissues are similarly
sensitive, the Agency prefers to use data from the target tissue (i.e.,
central or peripheral nervous system) rather than data from a surrogate
tissue (i.e., RBC). EPA's hazard identification for carbaryl states:
``Although the RBC BMDL10 for the more sensitive PND
11 rat is numerically the lowest (0.8 mg/kg) of the two
compartments, biologically the RBC BMDL10 is similar to
the brain BMDL10 (1.1 mg/kg). Since the brain is the
target tissue for the NMCs, and the brain BMDL10 1.1 mg/
kg is also protective of the surrogate and often more variable RBC
ChE measurements (BMDL10 0.8 mg/kg), then the brain
BMDL10 of 1.1 mg/kg is the appropriate PoD for both
children and adults in the carbaryl risk assessment (Ref. 82).''
Thus, for carbaryl, biologically the RBC and brain AChE inhibition were
basically equivalent where brain AChE inhibition is a direct measure in
a target tissue and RBC AChE inhibition is used as a surrogate for the
peripheral nervous system. This is quite different from the situation
with carbofuran where a significant difference was noted between RBC
and brain AChE inhibition, showing that RBC AChE inhibition (used as a
surrogate for the PNS) is more sensitive.
The approach used for carbaryl--i.e., relying on the central
estimate for purposes of comparison across age groups, and using
biological compartments and the lower limits for use as PoDs--is being
used by EPA in its carbofuran risk assessment. In addition, this
approach was used in the NMC cumulative risk assessments (CRA) and
single chemical risk assessments for multiple OPs. Thus, the Agency is,
in fact, being consistent in its hazard identifications among the AChE-
inhibiting pesticides.
With regard to the carbaryl children's safety factor, the available
brain and RBC dose-response data in PND11 pups include data from the
lower end of the dose-response curves. ORD's comparative ChE data with
carbaryl show that at the lowest dose at or near 20% inhibition in
brain and RBC AChE were observed. Although not ideal, the carbaryl data
provide information closer to the benchmark response of 10%, and
therefore allow for a reasonable estimation of the BMD10 and
BMDL10. This is distinctly different from ORD's data with
carbofuran in PND11 and PND17 pups where the 50% or greater RBC AChE
inhibition was observed at the lowest dose. Accordingly, the objection
is denied.
2. EPA's Mathematical Modeling Underlying the Calculation of a 4X
Children's Safety Factor. Petitioners argue that EPA committed numerous
errors in calculating the 4X children's safety factor. First,
Petitioners allege that, even assuming that RBC values are relevant,
EPA's conclusion that the RBC-related effects in the relevant
[[Page 59645]]
studies were four times more sensitive than brain effects is not
mathematically supportable. Referencing statistical analyses performed
by a contractor, they claim that ``[a]t most, the data support a 2X
safety factor, based on actual difference between brain and RBC
(ranging between 1 and 1.9).''
Second, the Petitioners claim that there are several technical
errors in the way EPA conducted the statistical modeling that formed
the quantitative support for the 4X children's safety factor. They also
object that the mathematical assumptions underlying EPA's modeling are
not justified and fail to support the 4X children's safety factor. In
this regard, they allege that EPA's children's safety factor was based
on calculations that (i) are not based on ``within animal
comparisons;'' (ii) have been applied incorrectly and inconsistently to
the data, which exaggerated the difference; (iii) overstate the
evidence for higher relative RBC sensitivity; and (iv) treated
carbofuran inconsistently as compared to other NMCs. They claim that by
removing the inconsistencies from EPA's data, the data yield a brain/
RBC ratio of 1.3, which confirms Petitioners' approach. These five
allegations are addressed separately below.
In support of these claims, the Petitioners offer allegations on
the points above, referencing two memoranda from Drs. R. Sielken and C.
Valdez-Flores (Exhibits 7, 8, 9) that generally describe and summarize
the analyses and modeling they conducted. The full analyses underlying
these memoranda were not included with the objections.
a. Objection/Hearing Request Subissue: Use of Within-Animal Brain to
RBC Inhibition Comparisons To Derive the Children's Safety Factor
i. Background. In the proposed rule, EPA explained its approach to
deriving an alternate to the default 10X children's safety factor. This
safety factor was calculated using the ratio of RBC and brain AChE
inhibition, using the data on administered dose for the PND11 animals
from the EPA-ORD studies and the FMC studies combined. In other words,
EPA estimated the BMD50 for PND11 animals for RBC and brain
from each quality study and used the ratio from the combined analysis,
resulting in a BMD50 ratio of 4.1X. EPA estimated the RBC to
brain potency ratio using EPA's data for RBC (the only reliable RBC
data in PND11 animals for carbofuran) and all available data in PND11
animals for brain. EPA's approach yields a ratio of about 4 fold.
EPA also compared the BMD50 ratios for PND17 pups (who
are slightly less sensitive than 11-day olds) in the EPA-ORD study, to
confirm that the observed differences in sensitivity between RBC and
brain were not unique to the PND11 data. The result of EPA's modeling
showed a BMD50 ratio of 3.3 \13\ between brain and RBC in
the PND17 pups.
---------------------------------------------------------------------------
\13\ EPA corrected a technical error identified in Petitioners'
comments, which resulted in a revised ratio of 2.6X, for the final
rule.
---------------------------------------------------------------------------
In their comments on the proposed rule, Petitioners presented
essentially the same arguments raised in this objection. They argued
that a more plausible and straightforward approach would be to compare
the RBC and brain AChE levels at the same time in the same rat when
these rats are exposed to carbofuran. The comments claimed that a
statistical evaluation of the experimental data on AChE inhibitions in
RBC and brain in rats due to carbofuran exposure had been performed by
Sielken & Associates, which showed that the percentage inhibition of
RBC AChE in a rat is almost the same as the percentage inhibition of
brain AChE in the rat. Although the results of the statistical analyses
were summarized in the comments, the underlying analyses were not
submitted.
In the final rule, EPA provided a detailed explanation of its
rationale for rejecting the Petitioners' approach (74 FR 23055; Ref.
85).
ii. Denial of hearing request. EPA is denying Petitioners' request
for a hearing on this objection for two reasons. First, as in its
comments, Petitioners failed to submit the underlying modeling
conducted in support of its assertions. Petitioners' consultant merely
asserts that the results are as presented in his summarized testimony.
In the absence of the underlying scientific analyses, these are
effectively no more than mere allegations or general contentions.
Hearings will not be granted on this basis alone. (40 CFR 178.32(b)(2);
see also 73 FR 42702 (July 23, 2008)(denying NRDC's hearing request on
objection that EPA's risk assessment was inadequate because EPA lacked
data on how pest strips were used in their homes, because ``NRDC
provided no factual information to support its claim''); 68 FR 46403,
46406-46407 (August 5, 2003) (FDA denied a hearing involving a
challenge to FDA's reliance on consumption pattern data because the
objector ``did not present any specific information to dispute P & G's
consumption pattern data; instead, [objector] simply asserted that
other consumption patterns were likely.''); accord Community Nutrition
Institute v. Novitch, 773 F.2d 1356, 1363 (DC Cir. 1985) (``Mere
differences in the weight or credence given to particular scientific
studies * * * are insufficient [to show a material issue of fact for a
hearing].'')).
Second, Petitioners' hearing request is inadequate because they do
not object to the basis EPA asserted in the final rule for rejecting
this approach. Specifically, Petitioners do not challenge EPA's
conclusion that their suggested approach is fundamentally flawed in
several regards, nor proffer evidence in support of that challenge.
Petitioners also do not challenge EPA's analyses, showing that the
results of their suggested approach are in fact consistent with EPA's
conclusions. As a consequence, Petitioners' objections are irrelevant,
and therefore immaterial, with regard to EPA's final tolerance
revocation regulation. The statute, however, requires that objections
be filed on the final rule not the proposal. By ignoring the EPA's
final rule on this subissue, Petitioners have failed to lodge a
relevant objection. Prior FDA decisions under its regulations are
instructive here. Objections and hearing requests were filed in
response to a food additive regulation covering the irradiation of
poultry. (62 FR 64102 (December 3, 1997)). The objector argued that the
addition of an anti-oxidant (ethoxyquin) to irradiated chicken prior to
the chicken's use in animal feeding studies compromised the studies
because the ethoxyquin would have decreased the level of lipid
peroxides in the chicken to levels found in chicken that had not been
irradiated. The FDA noted, however, that it had considered the question
of ethoxyquin's effect on lipid peroxide levels in the final rule and
determined that while ethoxyquin can retard the normal oxidation of
chicken fat to peroxides, ethoxyquin cannot reverse oxidation that has
already occurred. FDA denied the hearing request reasoning that because
the objector did ``not dispute FDA's explanation in the final rule as
to why addition of ethoxyquin did not compromise the CIVO studies, and
provided no information that would have altered the agency's conclusion
on this issue * * * there is no factual issue that can be resolved by
available and specifically identified reliable evidence'' (62 FR
64105). See also 53 FR 53176, 53191 (December 30, 1988) (FDA denied a
hearing request noting that given FDA's prior conclusion that the
studies relied upon by the objector were unreliable, the ``burden
shifted to [the objector] to maintain the viability of its
[[Page 59646]]
objection by proffering some information that called into question the
agency's conclusion on this matter.'')). Similarly, here, Petitioners
have not challenged the basis EPA asserted for rejecting their
suggested within-animal analyses, nor have they proffered any
information calling into question EPA's conclusion.
iii. Denial of objection. EPA notes that the Petitioners
recommended this approach of comparing the degree of inhibition for
each animal as part of their presentation to the carbofuran SAP. EPA
also addressed this approach, comparing RBC to brain in the same
animals, at the SAP and in the responses to the SAP report (Ref. 83).
It is notable that the SAP did not endorse this approach (Id.).
EPA's analyses of the Petitioners' approach identified several
significant deficiencies. First, the comparison suggested by the
Petitioners would require that EPA ignore existing data. This is
because only EPA's study of PND 11 animals contains both brain and RBC
data, so the comparisons suggested by the commenter can only be made
using that dataset. However, the dose levels in that study were so high
that the lower portion of the dose-response curve was missed. At these
higher doses, there is little difference between the levels of brain
and RBC inhibition. This phenomenon--i.e., that the relative
sensitivity of RBC compared to brain appears smaller at higher doses--
is also shown in multiple chlorpyrifos studies where blood or
peripheral measures of AChE inhibition are more sensitive than brain at
low to mid doses, but the tissues appear to be similar at higher doses.
Second, the Petitioners' approach is fundamentally flawed. The
Petitioners' suggested alternative relies exclusively on comparisons
between the degree of inhibition in the treated animals without any
regard to the doses at which the effects occurred. For example, one
animal may have shown, on average, 10% inhibition in the brain, when it
demonstrated 20% RBC inhibition. Under this approach, what would be
relevant would simply be the ratio of 1:2. But the Agency believes it
is critical to focus on the ratios of potency, which is the ratio of
the doses in the data that cause the same level of AChE inhibition. The
Agency's approach of comparing potencies is more directly relevant for
regulatory purposes than comparisons of average inhibition. This is
because dose corresponds more directly to potential exposures, which is
what EPA regulates (i.e., how much pesticide residue does a child
ingest). By comparison, the Petitioners' suggested reliance purely on
the average degree of inhibition provides no information that
corresponds to a practical basis for regulation.
Finally, the range of ratios of effects that the Petitioners
propose as an alternative is consistent with range of potencies that
EPA has calculated at these higher doses, so the Petitioners' results
do not ultimately contradict EPA's assessment, which is intended to
account for the effects at lower doses. Briefly, if the dose-responses
for RBC and brain inhibition were linear, ratios of inhibition would
equal ratios of BMDs. However, these dose-responses are not at all
linear; rather the available data demonstrate that brain and blood
dose-responses have somewhat different shapes. Thus, estimates of
relative effects at particular, relatively high, doses will not
determine the estimated ratios at lower doses. This is because the
dose-response curves begin to level off as they reach maximal
inhibition (i.e., no more inhibition is possible), so, at high doses,
there is almost no difference between the ratio of brain and RBC
inhibitions. Except at the lowest dose, which produced 50% AChE
inhibition, where the ratio is slightly greater than 2, the remaining
ratios are only slightly greater than 1. Given the inevitable
statistical noise in these measures, it is clear that the ratios
expected from EPA's modeling are substantially similar to the results
the Petitioner finds in its comparison between individuals.
Accordingly, the Petitioners' suggested comparisons at higher doses
provide no evidence of what occurs at lower doses; and thus provides no
evidence that demonstrates that EPA's modeling results at lower doses
is inaccurate.
b. Objection/hearing request sub issue: Scientific validity of
EPA's approach. The Petitioners object that EPA's approach has not been
established as scientifically valid. They claim that data for other
carbamates suggests that BMD50 s for the carbamates tend to
diverge more than the dose levels used to select the PoD (i.e., the
BMD10 s). In addition, they criticize EPA's approach for
incorrectly assuming that the relationship between BMD50 s
and BMD10 s is linear, which they claim overstates the
potential differences. They claim that these issues could be avoided by
adopting their suggested approach of using within-animal comparisons to
determine the relative sensitivity of RBC and brain AChE. The evidence
submitted in support of this subissue is the summary presented in the
objection.
i. Background. In the proposed rule, EPA explained that its
comparisons of the BMD50 s for brain and blood relied on an
assumption that the magnitude of the difference between RBC and brain
AChE inhibition is constant across dose. In other words, EPA assumed
that the RBC and brain AChE dose curves are parallel, even though there
are no data to test this assumption (73 FR 44873). In their comments,
the Petitioners criticized EPA for this assumption, and recommended
using ``within animal comparisons'' to avoid having to make this
assumption. In the final rule, EPA explained that its decision to rely
on comparisons of BMD50 s rather than BMD10 s was
because the RBC data for 10% inhibition levels was insufficient to
allow the Agency to generate the necessary estimates. EPA agreed that
the dose-response curves were not parallel at these lower doses, (i.e.,
that the relationship between BMD50 s and BMD10 s
was not linear) but that EPA lacked any data that would allow it to
make any other assumption. EPA nevertheless rejected the Petitioners'
suggested approach of relying on within-animal comparisons, because, as
described in the preceding objection, it is intrinsically flawed and
scientifically invalid.
ii. Denial of hearing request. A hearing on this subissue is not
appropriate because Petitioners' request is based on mere allegations,
general contentions, and speculation (40 CFR 178.32(b)(2)). No evidence
has been submitted on any of the issues raised in this objection.
Petitioners have provided no evidence that supports their assertion
that EPA's assumption that the dose-response curves will remain
parallel at lower doses overestimates the ratios. In the absence of
data at the low end of the dose-response curve, which Petitioners were
required to have developed, there is just as great a likelihood that
EPA's assumption underestimates the ratios. Petitioners have not cited
to any data from other carbamates to support their contention that
BMD50 s tend to diverge more than BMD10 s; the
objection fails to even identify the carbamate chemicals that
purportedly support this claim. Further, the claim is untimely, as it
was not raised as part of their comments on the proposed rule. For the
reasons discussed in Unit VI.D, EPA will not consider such information
in support of a request to justify a hearing.
In addition, a hearing on this objection is denied on the ground of
materiality (40 CFR 178.32(b)(1)). In the absence of EPA's assumption,
EPA would have no basis for deriving an alternate children's safety
factor. Thus, EPA would have to raise the children's safety factor from
4X to the statutory
[[Page 59647]]
default of 10X, rather than to lower the factor as the Petitioners
seek. As discussed at length in the preceding objection subissue, the
Petitioners' suggested alternative of within-animal comparisons is
scientifically invalid, and provides no useful basis for regulatory
action. Accordingly, if Petitioners establish that available
information does not support EPA's assumption that the dose-response
curves are parallel, then EPA is left with no valid scientific
information to determine the correct dose-response curve at lower
doses, or to establish a BMD10 (21 U.S.C. 346a(b)(2)(C)).
Because deviation from a 10X children's safety factor requires some
``reliable data'' on the shape of the dose response curve for RBC AChE,
Petitioners' objection on EPA's low dose-response curve assumptions, in
combination with the failure to provide a valid alternate approach
would result in a higher children's safety factor, and a conclusion
that EPA has underestimated carbofuran's risks.
iii. Denial of objection. EPA disagrees that its approach is not
scientifically valid. The models used to develop the BMD estimates have
been repeatedly reviewed and approved by the SAP (Refs. 34, 35). The
most recent occasion was the February 2008 carbofuran SAP, which
concluded that ``[t]he dose-response analysis done by the Agency for
the EPA-ORD PND11 study was appropriate and led to a very uncertain
BMD10 * * * This [assumed dose-response] curve fit well in
the region where there were data, but there was no way to validate it
at low doses'' (Ref. 36 at 54).
EPA acknowledges that it lacks information to confirm its
assumption that the dose-response curves remain parallel at lower
doses. EPA believes this is the most reasonable assumption, given the
absence of information at low doses, since it neither presumes that RBC
inhibition will increase or decrease at lower doses. Contrary to
Petitioners' naked assertion that EPA's approach overestimates the
difference, there is no inherent reason to expect that EPA's assumption
would overestimate or underestimate the difference between
BMD50 s and BMD10 s. If indeed data were to show
that EPA's assumption overestimated the difference--and Petitioners
have submitted none--it would only be as a result of the animal
biology, as there is no indication in the mathematical modeling that it
overestimates the difference in any way. The mathematical relationship
between BMD50 s and BMD10 s certainly provides no
hint that there might be a bias. In this regard, it is notable that the
February 2008 SAP concluded that `[w]hat the Panel observed at the low
end [of the dose-response curve] made it tempting to assume linearity
at this part of the dose-response curve'' (Ref. 36 at 55).
Regarding the Petitioners' claim that data for other carbamates
suggests that BMD50 s for the carbamates tend to diverge
more than the dose levels used to select the PoD (i.e., the
BMD10 s). EPA cannot confirm the accuracy of this
allegation, as Petitioners have provided neither data nor any
explanation of a biological basis to support this claim. Nor is EPA
able to substantiate this claim based on the information currently
available. However, there is no a priori reason to expect such a
systematic divergence between ratios of BMD50's and ratios
of BMD10 s for blood and brain, based either on biology or
the mathematical relationship between BMD50's and
BMD10 s. It is actually far more probable that the variation
from chemical to chemical (due both to real variation among chemicals
and to statistical sampling noise) would be large enough to make a
conclusive determination from data difficult.
c. Objection/hearing request sub issue: Combining data from
different toxicological studies--i. Background. In its risk assessment,
EPA relied on all of the valid data from the available studies to
calculate the estimates that served as the PoD, and to calculate the
estimates of BMD50 s that serves as quantitative support for
derivation of the 4X children's safety factor.
For purposes of the PoD, the Agency used a meta-analysis that
combined valid data from all available studies to calculate the
BMD10 and BMDL10 for pups and adults; this
analysis includes brain data from studies where either adult or
juvenile rats or both were exposed to a single oral dose of carbofuran.
The quality brain AChE data from the three studies (2 FMC, 1 EPA-ORD)
conducted with PND11 rats, in combination, provides data to describe
both low and high doses. By combining the three studies in PND11
animals together in a meta-analysis, the entire dose-response range is
covered.
EPA also combined studies in calculating the 4X children's safety
factor. EPA derived the ratio of RBC and brain AChE inhibition using
the data on administered dose for the PND11 animals from the EPA-ORD
studies and the FMC studies combined. In other words, EPA estimated the
BMD50 for PND11 animals for RBC and brain from each quality
study and used the ratio from the combined analysis, resulting in a
BMD50 ratio of 4.1X. EPA estimated the RBC to brain potency
ratio using EPA's data for RBC (the only reliable RBC data in PND11
animals for carbofuran) and all available data in PND11 animals for
brain.
In their comments on the proposed rule, Petitioners claimed that
EPA's decision to combine data for different strains of rats, sexes,
experiments, laboratories, dates, dose preparations, rat ages, and
times between dosing and AChE measurement, is problematic, claiming
that these differences in study design severely limit the validity of
EPA's comparisons. Further, they alleged that differences in data and
methods EPA used to estimate its BMD50 (brain) and
BMD50 (RBC) caused EPA to overestimate the difference
between brain and RBC, and thereby invalidating any comparison of the
estimates. Specifically, Petitioners were concerned that the datasets
from the six studies EPA used for brain differ not only because they
were from different studies, but also because the data were taken at
different times ranging from 15 minutes to 4 hours after dosing.
EPA responded to these comments in full during the rulemaking (74
FR 23055-23057 (May 14, 2009); Ref. 85). Petitioners referenced these
comments in their objections, but presented no further argument or
evidence on any of these points. Because Petitioners originally raised
this claim also with respect to the derivation of EPA's PoD, even
though they only raise it in this objection here, the Agency responds
to both points below.
ii. Denial of hearing request. The Petitioners have not met the
requirements for a hearing on this subissue. Petitioners have not
challenged the basis EPA asserted for rejecting their suggested within-
animal analyses, and have therefore failed to lodge a relevant
objection. Both EPA and FDA precedent make clear that when the agency
substantively responds to comments on the proposal, the commenter may
only keep that issue alive in its objections by addressing the agency's
substantive response (40 CFR 178.32(b)(3)). Nor have they proffered any
evidence that calls the substance of EPA's conclusions into question. A
hearing is not warranted on the basis of mere denials or contentions
(40 CFR 178.32(b)(2)). See 73 FR 42698-42699 (When an objector does not
challenge EPA conclusions in the section 408(d)(4)(iii) order but
rather challenges some prior conclusion that was superseded by the
section 408(d)(4)(iii) order, the objector has not raised a live
controversy as to an issue material to the section 408(d)(4)(iii)
order); 53 FR 53176, 53191 (December 30, 1988) (FDA denied a hearing
request noting that given FDA's prior conclusion that the
[[Page 59648]]
studies relied upon by the objector were unreliable, the ``burden
shifted to [the objector] to maintain the viability of its objection by
proffering some information that called into question the agency's
conclusion on this matter.'')).
Second, this objection is not material. In the case of carbofuran,
EPA used a sophisticated analysis of multiple studies and datasets to
develop the PoD for the carbofuran risk assessment. Instead of this
analysis, EPA could simply have followed the general approach laid out
in its BMD policy (Ref. 100), which is used in the majority of risk
assessments. Under this general approach, EPA would regulate using the
most sensitive effect, study, and/or dataset. If the Agency chose not
to combine the data in its analyses, as the commenters' suggested, data
collected at or near the peak time of effect (i.e., 30 minutes) would
in fact provide the more relevant datasets. If this more simple
approach were taken, in accordance with BMD guidance, EPA would select
the lowest BMDL10. Assuming the commenters' values were
used, EPA would have selected a PoD of 0.009 mg/kg/day, instead of the
0.03 mg/kg/day that EPA is currently using in its risk assessment. A
lower PoD of 0.009 mg/kg/day would significantly increase carbofuran's
level of estimated risk.
iii. Denial of objection. In general, EPA believes that
consideration of all available data is the scientifically more
defensible approach, rather than the selective exclusion of reliable
data. The Agency's Draft BMD Guidance says the following: ``Data sets
that are statistically and biologically compatible may be combined
prior to dose response modeling, resulting in increased confidence,
both statistical and biological, in the calculated BMD'' (Ref. 76). The
SAP has reviewed and approved EPA's practice of combining data from
studies numerous times (Refs. 34, 35, 36). Most recently, as part of
the carbofuran SAP, the SAP was fully aware that the Agency was
planning to derive BMD estimates from data sets using different strains
of rats (Ref. 36). Accordingly, the Agency's carbofuran analysis has
included all available, valid data in its analysis.
By contrast, the Petitioners' suggested analysis ignores relevant,
scientifically valid data. Their analysis left out the 30-minute data
from MRID no. 47143705 (Ref. 2), but provided no rationale as to why it
would be appropriate to selectively exclude data from the time frame in
this study most relevant to the risk assessment (i.e., peak AChE
inhibition). The Petitioners' analysis of the individual datasets from
this study showed that at 30 minutes the females and males provide
BMDL10 s of 0.009 mg/kg/day and 0.014 mg/kg/day,
respectively. When the datasets were combined, inclusion of the 30-
minute timepoint from MRID no. 47143705 decreased the BMDL10
from 0.033 mg/kg/day to 0.030 mg/kg/day.
Although the Petitioners complain that EPA's approach of combining
data across multiple studies is scientifically inappropriate, the
Petitioners themselves combined the results of analysis from four
datasets in the information presented with their comments and
referenced in their objections. Indeed, it is notable that most of the
criticisms raised by the Petitioners also apply equally to the
Petitioners' own analysis, as described in more detail in EPA's
Response to Comments document (Ref. 85).
The Petitioners are also incorrect that differences in the data
available for brain and RBC are so great as to invalidate comparisons
of the BMD estimates. EPA used all the data available in each case, and
used a hierarchical model to account for variability of the BMD among
laboratories for the brain endpoint, which the SAP has explicitly
reviewed and approved numerous times (Refs. 34, 35, 36).
The Petitioners are correct that data from both sexes were combined
for brain but only male data were used for RBC. However, EPA first
performed an evaluation of the differences between the sexes. EPA
combined data from males and females only after showing that they did
not respond differently.\14\ The only remaining study to examine AChE
activity in RBC in PND11 animals, after FMC's flawed studies were
eliminated, contained only male animals. Both BMD50 s for
brain and RBC in adults were based on 15 minutes, the minimum time
interval after dosing when a sample was taken, in each dataset.\15\
This is also true for the brain endpoint in PND11 animals. However, the
only study available of the RBC endpoint in PND11 animals was conducted
at 40 minutes after dosing, and did not include a recovery time course
study.
---------------------------------------------------------------------------
\14\ See pp. 34-35 in the brain document dated October 25, 2007
for adults, pp. 47-48 in the same document for PND11 animals; p. 15
in the RBC document dated October 23 for adults.
\15\ See Oct. 5, 2007 reports, page 8 (for the values of the
time interval) and page 63 (setting the parameter delta to the
minimum non-zero value for that interval) in the RBC report, and
page 9, and page 45 for the corresponding report for Brain.
---------------------------------------------------------------------------
EPA believes that its decision to combine data for purposes of its
BMD50 estimates supporting the children's safety factor is
equally appropriate, and any differences in the way in which the
studies were conducted did not impact the validity of EPA's analyses.
For example, one of Petitioners' complaints was that it was
inappropriate to combine studies because the data in the studies were
taken at different times, ranging from 15 minutes to 4 hours after
doses. EPA responded to the allegation that this was problematic by
conducting the analysis that the Petitioners claimed should have been
done to support this. As explained in the final rule, although EPA
disagreed with the Petitioners' contention that this was necessary or
appropriate, EPA conducted the Petitioners' suggested analysis, and
used the dose-time-response model to extrapolate BMD50 s to
develop a common point of comparison between all studies. Specifically,
EPA extrapolated the PND11 brain analysis to estimate BMD50
for 40 minutes after dosing for comparison with the existing PND11 RBC
BMD50, and extrapolated the PND11 RBC BMD50 to 15
minutes after dosing for a range of assumed recovery half-lives, for
comparison to the existing PND11 brain BMD50. The results
are provided in (Refs. 24, 25). In either approach, the estimate of the
RBC to brain potency ratio in PND11 animals is increased, and EPA's
safety factor would correspondingly increase to reflect that larger
difference. For example, when the PND11 brain BMD50 is
extrapolated to 40 minutes, the RBC to brain potency ratio grows to 4.7
(Ref. 24 at 46), and when the PND11 RBC BMD50 is
extrapolated to 15 minutes, using a range of estimates for the recovery
half-life of the RBC endpoint, the RBC to brain potency ratio ranges
from 4.2 to 4.6 (Ref. 24). The Petitioners' approach would therefore
support a children's safety factor of 5X rather than the 4X EPA is
currently applying in its risk assessments. Nevertheless, EPA continues
to believe that its current use of a 4X factor reflects the most
reliable interpretation of existing quality data.
Although it is true that EPA's BMD50 for brain was based
on data from 6 datasets while the RBC BMD50 was based on a
single study, this is because scientifically acceptable RBC data are
only available from a single study. As discussed, the fact that EPA
used all available data sets in its modeling does not affect the
validity of its modeling (Ref. 76).
For all of the foregoing reasons, this objection is denied.
d. Objection/hearing request sub issue: Technical Flaws in EPA's
statistical comparisons. In their objections, Petitioners claim to have
found a number of technical errors and inconsistencies in how the
modeling
[[Page 59649]]
was conducted. Correcting for these errors, they claim, shows that the
BMDs for brain and RBC data are essentially the same, which was
consistent with the results of modeling conducted by the Petitioners
when evaluating the individual animal data. Specifically, Petitioners
allege that the approach EPA used to estimate BMD50 s for
carbofuran is inconsistent with its ``meta-analysis'' approach of
combining studies. The Petitioners also argued that EPA's modeling
failed to account for significant difference in study methodologies
(e.g., time to sacrifice following dosing). For example, EPA's
BMD50 (Brain) is calculated at 15 minutes after exposure
starts whereas EPA's BMD50 (RBC) is calculated at 40 minutes
after exposure starts. EPA's BMD50 (brain) is based on 6
studies whereas EPA's BMD50 (RBC) is based on 1 study, and
the dose-time-response modeling methodology for combined studies and
EPA's BMD50 (brain) is different than the dose-time response
modeling methodology for a single study and EPA's BMD50
(RBC). Petitioners also allege that EPA applied its dose-time-response
model inconsistently between the brain and RBC calculations, alleging
that the power was fixed to 1.00 for brain, but estimated for RBC.''
They also criticize the modeling on the grounds that EPA did not: (1)
Account for differences between the combined datasets; (2) develop a
protocol supporting its approach; (3) clearly document its method; (4)
accurately document model parameters; (5) rely on a plausible dose-
response model, or (6) report its data accurately or transparently.
They further allege that ``removing all of these inconsistencies in
methodology results in a ratio of 1.3, which corresponds with the ratio
that the Petitioners claim to have obtained based on their within
animal comparisons.
Petitioners have provided neither further details of their concerns
than the explanation above, nor any other evidence to support this
objection.
i. Background. EPA addressed all of the commenters' claimed
inconsistencies in its final rule and Response to Comments document (74
FR 23055-23056; Ref. 85 at 61-62). For the majority of these claimed
flaws and inconsistencies, EPA explained that the Petitioners had
misunderstood EPA's analyses, or that the Petitioners' were incorrect.
However in response to certain allegations, EPA conducted new analyses
to determine whether the suggested alternative approaches would make
any significant difference in EPA's modeling outcomes.
Petitioners have provided little detail in their objections on the
issues they intend to raise in their testimony; in most instances, they
simply allege that EPA's modeling was incorrect. But as the objections
reference the Petitioners' comments on the proposed rule, EPA assumes
that they intend to raise only the points previously discussed in their
comments.
ii. Denial of hearing request. The Petitioners' request for a
hearing on the issues raised in this objection is denied on two bases.
First, Petitioners have not challenged the substance of EPA's response
to their comments or submitted evidence that calls the substance of
EPA's conclusions into question. As previously explained, their failure
to challenge the actual basis of EPA's final rule affects the
materiality of the objection and hearing request (40 CFR 178.32(b)(3)).
See 73 FR 42698-42699 (When an objector does not challenge EPA
conclusions in the section 408(d)(4)(iii) order but rather challenges
some prior conclusion that was superseded by the section 408(d)(4)(iii)
order, the objector has not raised a live controversy as to an issue
material to the section 408(d)(4)(iii) order) 53 FR 53176, 53191
(December 30, 1988) (FDA denied a hearing request noting that given
FDA's prior conclusion that the studies relied upon by the objector
were unreliable, the ``burden shifted to [the objector] to maintain the
viability of its objection by proffering some information that called
into question the agency's conclusion on this matter.'')). Further,
Petitioners have not rebutted, or even acknowledged, the additional
analyses EPA undertook at their suggestion, and discussed in the final
rule, which ultimately provided further support for EPA's position. For
example, in response to the complaint that EPA should have generated a
new dose-response model in order to calculate the BMD50 s
for brain and RBC, EPA conducted the suggested calculation, and under
that analysis, the result is the same as that EPA originally
calculated. Similarly, in response to the complaint that EPA should
have used the dose-time-response model to extrapolate BMD50
s to develop a common point of comparison between all studies, EPA
conducted that analysis and described it in the final rule (74 FR
23055-23056 (May 15, 2009)). The result of this reanalysis supported a
higher children's safety factor than EPA's 4X. But rather than
challenge the new analysis, Petitioners simply repeat the assertions
made in their comments. Because the objections on these points fail to
account for EPA's analyses, the objections are contradicted by the
record, and accordingly, fail to demonstrate a factual dispute (40 CFR
178.32(b)(1)). See 73 FR 42698-42699 (Denying NRDC hearing where
objection reiterated claims premised on conclusions in EPA's
preliminary risk assessment, rather than objecting to EPA's conclusions
in the revised assessment prepared for the petition denial); 49 FR 6672
(February 22, 1984) (no hearing if claim based on demonstrably false
premise); 57 FR 6667 (February 27, 1992) (``A hearing must be based on
reliable evidence, not on mere allegations or on information that is
inaccurate and contradicted by the record'').
Second, as in their comments, Petitioners failed to submit the
underlying modeling they claim to have conducted in support of their
objections. Petitioners' consultants merely assert that the results are
as presented in their summarized testimony. In the absence of the
underlying scientific analyses, these are effectively no more than mere
allegation or general contentions. Hearings will not be granted on this
basis. (40 CFR 178.32(b)(2); see also 68 FR 46403, 46406-46407 (August
5, 2003) (FDA denied a hearing involving a challenge to FDA's reliance
on consumption pattern data because the objector ``did not present any
specific information to dispute P & G's consumption pattern data;
instead, [objector] simply asserted that other consumption patterns
were likely.''); accord Community Nutrition Institute v. Novitch, 773
F.2d 1356, 1363 (DC Cir. 1985) (``Mere differences in the weight or
credence given to particular scientific studies * * * are insufficient
[to show a material issue of fact for a hearing].'').
iii. Denial of Objection. For all of the reasons discussed in the
final rule and Response to Comments documents, this objection is
denied. A summary of EPA's bases, which were discussed in detail in
both the final rule and Response to Comments document, is presented
below.
Consistency of EPA approach. In their comments, the Petitioners'
explained that the alleged inconsistency with which they were concerned
was that ``EPA attempts to extrapolate a BMD10 to a
BMD50 without refitting the data. That is, EPA uses the
dose-response model obtained for the BMD10 rather than
obtaining a new model for BMD50.'' They claimed this was
``especially troublesome since EPA has expressly stated that the model
obtained for BMD10 (RBC) is unreliable.''
[[Page 59650]]
The Petitioners' allegation on this point is incorrect. The model
itself does not need to change in order to develop a BMD50.
Whether one wants to estimate the BMD10 or the
BMD50, one would use the same underlying model. EPA simply
developed a mathematical expression to adjust parameter values for that
fitted model so that, for any given benchmark response level (in
particular, for 10% or 50% inhibition), the corresponding BMD could be
estimated as a parameter in that model. The same expression makes it
possible to compute a BMD for any given response level from estimates
based on any other response level. Mathematically, it is not necessary
to refit the model to the data to estimate different BMD levels.
However in response to the comments, EPA conducted their suggested
calculation, and the ratio of brain to RBC BMD50 s in this
new analysis is the same as the ratio EPA calculated by using the
mathematical expression (Refs. 24, 25). Both provide a ratio of brain
to RBCs BMD50 of 4X. Specifically, in the just cited
documents above, the values are for PND11 brain BMD50 are
0.35 (Ref. 24 at 40) and for RBC, 0.086 (Ref. 25 at 20), resulting in a
ratio of 4.09.
With regard to the EPA's purported statement that the
BMD10 model is unreliable, the Petitioners misconstrued
EPA's statement. EPA stated that it cannot reliably estimate the RBC
BMD10 and BMDL10 in pups because it lacks data at
low doses, not because its model is unreliable. Given the greater
amount of data, the estimate for the BMD50 is substantially
better supported, and thus, less uncertain, than the estimate of the
BMD10.
Differences in study methodologies. Both BMD50 s for
brain and RBC in adults were based on 15 minutes, the minimum time
interval after dosing when a sample was taken, in each dataset.\16\
This is also true for the brain endpoint in PND11 animals. However, the
only study available of the RBC endpoint in PND11 animals was conducted
at 40 minutes after dosing, and did not include a recovery time course
study.
---------------------------------------------------------------------------
\16\ See Oct. 5, 2007 reports, page 8 (for the values of the
time interval) and page 63 (setting the parameter delta to the
minimum non-zero value for that interval) in the RBC report, and
page 9, and page 45 for the corresponding report for Brain.
---------------------------------------------------------------------------
As noted in the previous objection response, EPA used the dose-
time-response model to extrapolate BMD50 s to develop a
common point of comparison between all studies. Using that approach
would support a children's safety factor of 5X rather than the 4X EPA
has applied.
Although it is true that EPA's BMD50 for brain was based
on data from 6 datasets while the RBC BMD50 was based on a
single study, this is because scientifically acceptable RBC data are
only available from a single study. As discussed in the preceding
objection response, the fact that EPA used all available data sets in
its modeling does not affect the validity of its modeling (Ref. 76).
Inconsistent application of model. EPA did not apply its model
inconsistently; the difference to which the Petitioners refers results
from the differences between the available data. In order to generate
an estimate of the power parameter, data at both extremes of the dose-
response curve are necessary. Despite the comparatively greater amount
of brain inhibition data, the brain data did not provide information at
both extremes of the curve. A value of 1.00 is the standard default in
this situation for all the NMC dose-response analyses. Moreover,
despite the limited information at the extremes of the dose-response
curve for estimating power in the brain data, a power parameter of 1.00
is consistent with the available brain data. By contrast, because the
available RBC data provides the necessary information at higher doses,
the power in the RBC data could be directly estimated and was
significantly less than 1.0.
EPA is unable to comment on the analyses referenced in the
Petitioners' objections as they failed to provide them. However, EPA
has previously explained the reasons for rejecting the suggested
analysis based on brain RBC comparisons within the same animal. This is
discussed at length in the final rule and response to comments, as well
as Unit VI.E.2.a of this Order.
f. Objection/hearing request sub issue: Consistency in approach
between carbofuran and other NMC chemicals--i. Background. In their
comments on the proposed rule, the Petitioners argued that EPA's
approach to deriving carbofuran's children's safety factor was
inconsistent with its approach to deriving the safety factors for other
NMC pesticides. They identified only three specific chemicals:
Aldicarb, oxamyl, and carbaryl. With respect to aldicarb they argued
that although the relative potency of carbofuran is less than aldicarb,
the uncertainty factors assigned by EPA presuppose that carbofuran is
ten times more toxic that aldicarb. They claim that the aldicarb data
show that by all objective measures of toxicity, aldicarb is nearly
twice as acutely toxic as carbofuran across all species tested. They
further claim that an alternative approach to relative rankings of
carbamates proposed by the SAP in its assessment of the NMCs (which
also considered the rate of recovery) also showed aldicarb having
approximately twice the potency of carbofuran. They further alleged
that the children's safety factor for carbaryl was inconsistent with
the safety factor applied to carbofuran. Finally, the Petitioners
compared the aPAD, aRfD, and uncertainty factors for oxamyl, aldicarb,
and carbaryl, concluding that these were inconsistent with EPA's
conclusions for carbofuran.
EPA responded to these comments in both the final rule and the
accompanying response to comments document (74 FR 23058 (May 15,
2009)).
In their objections, Petitioners have not identified any specific
facts that they believe demonstrate inconsistency. They merely allege
that the ``relative potency of carbofuran as compared to other N-methyl
carbamates does not correspond with OPP's aPAD for carbofuran relative
to those same compounds.''
ii. Denial of hearing request. A hearing is denied on this subissue
because there is no disputed factual matter for resolution at a
hearing. There is no dispute concerning the children's safety factors
that EPA applied to the other carbamates, nor how EPA derived those
safety factors. Thus, the only question is whether it was reasonable
for EPA to account for the fact that other chemicals had a greater
amount of toxicity data, and therefore greater uncertainty, in
determining the appropriate children's safety factor, when the statute
requires EPA to account for ``the completeness of the data'' (21 U.S.C.
346a(b)(2)(C)). This question requires the application of a legal
standard to undisputed facts. Hearings are not appropriate on questions
of law or policy (40 CFR 178.32(b)(1)). See, 73 FR 42706-42707)
(denying NRDC hearing request when the only question raised was whether
a human study using only adult males met the regulatory requirement of
``scientifically valid and relevant data''. FDA has repeatedly
confirmed that the application of a legal standard to undisputed facts
is a question of law for which a hearing is not required. (See, e.g.,
68 FR 46403, 46406 n.18, 46408, 46409 (August 5, 2003) (whether facts
in the record show there is a reasonable certainty of no harm is a
question of law; whether a particular effect is a ``harm'' is a
question of law)).
In addition, Petitioners have not challenged the substance of EPA's
response to their comments, but simply reiterated their comments on the
proposed rule. Accordingly, a hearing is
[[Page 59651]]
not warranted, as the objection is subissue is irrelevant, and
therefore immaterial, with regard to EPA's final tolerance revocation
regulation (40 CFR 178.32(b)(3)). See 73 FR 42698-42699 (July 23, 2008)
(When an objector does not challenge EPA conclusions in the section
408(d)(4)(iii) order but rather challenges some prior conclusion that
was superseded by the section 408(d)(4)(iii) order, the objector has
not raised a live controversy as to an issue material to the section
408(d)(4)(iii) order; 53 FR 53176, 53191 (December 30, 1988) (where FDA
responds to a comment in the final rule, repetition of the comment in
objections does not present a live controversy unless the objector
proffers some evidence calling FDA's conclusion into question)).
Nor have they submitted evidence that calls the substance of EPA's
conclusions into question. Petitioner's entire argument concerning this
issue is a single conclusory sentence. A hearing will not be granted on
``mere allegations'' or ``general contentions.'' (40 CFR 178.32(b)(2))
(See 53 FR 53176, 53199 (December 30, 1998)) (``Rather than presenting
evidence, [the objector] asserts that FDA did not adequately justify
its conclusions. Such an assertion will not justify a hearing.'').
iii. Denial of objection. Although it is unclear which precise
chemicals the Petitioners believe demonstrate that EPA was
inconsistent, the only ones on which any allegations were arguably
presented were those identified in their comments on the proposed rule:
aldicarb, carbaryl, and oxamyl. Accordingly, EPA denies this objection
for the same reasons that EPA explained in its final rule and comment
responses.
In their comments, the Petitioners provided information on the oral
LD50 in rat and the BMDL10 for AChE in rat brain
or human RBC. The comments also provided uncertainty factors for the
three NMCs, the respective aRfD \17\ or aPAD \18\ and the cumulative
risk assessment oral potency factor. The LD50 and
BMDL10, values provided are not completely accurate.
---------------------------------------------------------------------------
\17\ aRfD is the acute reference dose.
\18\ aPAD is the acute RfD adjusted for the Children's Safety
Factor.
---------------------------------------------------------------------------
The allegations and the supporting information contained in
Petitioners' comments were inaccurate. For example, the LD50
values in the oxamyl RED were 3.1 mg/kg (male) and 2.5 mg/kg (female),
rather than 30 mg/kg as the Petitioners claimed. Further, the Agency's
recent hazard assessments of carbaryl and aldicarb are each consistent
with EPA policies and practice, as well as with the Agency's approach
to the assessment of carbofuran.
The Petitioners' assertions regarding aldicarb were based on an
earlier assessment. At the time the Agency conducted the assessment to
which the commenters refer, the Agency was unaware of the difference in
sensitivity between PND17 and PND11 animals. Since EPA became aware of
the differences, EPA has required the aldicarb registrant to conduct a
CCA study in PND11 rats; the Agency anticipates the receipt of this
study and the companion range-finding and time course studies in 2009.
In the absence of these data, EPA will apply the statutory default
children's safety factor to account for the additional sensitivity of
PND11 animals, because the Agency lacks any ``reliable data'' that
could be used to derive a reduced factor that EPA could determine will
be ``safe for infants and children.''
With regard to the carbaryl children's safety factor, the available
brain and RBC dose-response data in PND11 pups include data from the
lower end of the dose-response curves. ORD's comparative AChE data with
carbaryl show that at the lowest dose 20% or near 20% inhibition in
brain and RBC AChE was observed. Although not ideal, the carbaryl data
provide information closer to the benchmark response of 10%, which
allows for a reasonable estimation of the BMD10 and
BMDL10. This is distinctly different from ORD's data with
carbofuran in PND11 and PND17 pups where 50% or greater RBC AChE
inhibition was observed at the lowest dose.
Petitioners' other comparisons are equally inapposite. The
LD50, BMDL10, and relative potency factor from
the cumulative risk assessment are each measures of chemical potency.
Thus, these calculations provide reasonable comparisons of the relative
potency of aldicarb, carbofuran, and oxamyl. However, the Petitioners'
allegations were based on comparisons of the aPAD, aRfD, and
uncertainty factors, which are not measures of potency and should not
be interpreted as such (Ref. 79). The magnitude of the uncertainty
factors is intended to account for uncertainty in the available data
for a particular chemical. For example, it is standard practice to
apply a 10X uncertainty factor for extrapolation from animals to humans
when ethically and scientifically sound human data are not available
for the pesticide of interest. And this explains the difference in the
uncertainty factors applied to the three chemicals. Deliberate dosing
studies in human subjects conducted with aldicarb and oxamyl were
reviewed and accepted by the HSRB for both scientific validity and
ethical conduct. This is not the case for carbofuran. As discussed
below in Unit VI.G, the HSRB concluded that the carbofuran study was
not sufficiently scientifically robust for use in the risk assessment.
Therefore, there is less uncertainty in the aldicarb and oxamyl risk
assessments since quality data are available in humans and the
interspecies factor can be reduced or removed for these chemicals.
There are no comparable data for carbofuran.
Accordingly, this objection is denied.
F. Objections to EPA's Drinking Water Exposure Assessments.
Petitioners raise separate objections to EPA's estimates of
drinking water exposures from contaminated ground water and to the
estimates from contaminated surface water. In each objection,
Petitioners argue that, based on newly proposed restrictions submitted
as part of their objections, the exposure estimates will be
significantly lower than EPA's estimates in the final rule.
1. Objections relating to groundwater exposure estimates.
Petitioners raise several challenges to the ground water concentration
estimates in the final rule. They allege that EPA's estimates are not
based on the best available data, but on obsolete data and overly
conservative assumptions that are inappropriate because use has been
prohibited in all areas like those seen in these data. The objection
also claims that the requirements in the new registration proposals to
require setbacks from all drinking water wells ranging between 100 and
1,000 feet will ensure that all potential groundwater exposures will be
below the level of concern. In support of this objection three analyses
were submitted in Exhibits 12, 13, and 14.
a. Objection/hearing request subissue: Reliance on the results of
the prospective ground water study (PGW) and historical monitoring to
validate groundwater exposure estimates. The Petitioners object that
EPA should not have relied for validation on their PGW study or
historical monitoring data. They argue that these data are from a
period when use was an ``order of magnitude greater.'' Additionally
they allege that all areas like those seen in the PGW have now been
removed from the carbofuran label, and so the study results do not
accurately reflect current risks. In support of this objection,
Petitioners reference their comments on the proposed rule, and Exhibit
12.
i. Background. In the proposed rule, EPA relied on a drinking water
assessment that used both monitoring data for carbofuran and modeling
[[Page 59652]]
methods (Refs. 13, 42, 44, 47, 67). Regarding the potential exposure
from contaminated groundwater, the Agency concluded that drinking water
taken from shallow wells is highly vulnerable to contamination in areas
where carbofuran is used around sandy, highly acidic soil, although
sites that are less vulnerable (e.g., deeper aquifer, higher organic
matter) could still be prone to have concentration exceeding acceptable
exposures. EPA concluded that the results of its modeling were
consistent with the results of the available monitoring data, including
a PGW study conducted by FMC in the 1980s, when scaled to reflect the
current lower rates of application (73 FR 44881).
In their comments, the Petitioners complained that EPA's reliance
on the PGW was inappropriate because that study no longer reflected
current conditions. Petitioners also summarized the results of their
``National Leaching Assessment'' which used PRZM and ``databases
specifically created to provide access to all necessary inputs for a
national scale PRZM modeling.'' They claimed that after accounting for
the use prohibitions on their September 2008 label, the maximum 1-in-10
year peak concentrations in all potential carbofuran use areas is 1.2-
1.3 ppb, while expected concentrations in most areas covered by this
assessment are below 1.0 ppb. Neither the ``National Leaching
Assessment'' nor the ``National Pesticide Assessment Tool'' upon which
the assessment appears to have been based, were submitted to EPA as
part of the Petitioners' comments.
In the final rule, EPA revised the assessment conducted for the
proposed rule in response to the FMC comments submitted during the
comment period, which requested cancellation of the use on a number of
crops and imposed a number of restrictions intended to address the
potential for groundwater contamination. These restrictions included
use prohibitions in certain states, and well setbacks. Taking these
into account, ground water concentrations were estimated for all
remaining crops on carbofuran labels, using two new Tier 2 scenarios.
Based on a new corn scenario in Wisconsin, representative of
potentially vulnerable areas in the upper Midwest where use remained,
EPA estimated one-in-ten year concentrations for ground water source
drinking water of 16 to 1.6 x 10-3 ppb, for pH 6.5 and 7,
respectively. Well setback prohibitions of 50 ft were proposed on the
new label for the flowable and granular formulations in select counties
in Kentucky (7 counties), Louisiana (1 county), Minnesota (1 county),
and Tennessee (1 county). Analysis of the impact of these setbacks for
the use on corn indicated that the setbacks would not reduce
concentrations significantly at locations where exposure to carbofuran
in ground water is of concern because at acid pHs, carbofuran does not
degrade sufficiently during the travel time from the application site
to the well to substantially reduce the concentration.
EPA concluded that the results of the revised corn modeling were
consistent with the PGW. Using higher use rates than currently
permitted, the peak concentration measured in the PGW study was 65 ppb;
when scaled to current use rates, the estimated peak concentration was
11 ppb. The final rule explained that EPA's modeling is also consistent
with a number of other targeted groundwater studies conducted in the
1980s showing that high concentrations of carbofuran can occur in
vulnerable areas; the results of these studies as well as the PGW study
are summarized in References 13 and 67 (74 FR 23079).
ii. Denial of hearing request. For this hearing request, the
Petitioners have failed to proffer evidence, which would, if
established, resolve a material issue in their favor. First,
Petitioners' evidentiary proffer does not support their contention, and
consequently, EPA is unable to conclude that there is a reasonable
possibility that the issue could be resolved in its favor (40 CFR
178.32(b)(2)). Petitioners' own experts relied on the PGW to validate
the modeling submitted in support of this objection and to demonstrate
the safety of the tolerances. The Executive Summary of the National
Carbofuran Leaching Assessment states
``[a] model validation study was conducted in which the results
of a prospective groundwater monitoring (PGW) study conducted for
cabofuran in Maryland from 1981-1983 were compared to the model
simulations that most closely matched the PGW study site in terms of
location, soil texture, organic carbon content, and pH. The annual
peak concentrations during the simulation are on the order of 9 to
11 ppb, which are similar to the measured concentrations in the PGW
study (9 to 10 ppb after adjusting for application rate). The
validation provides context that the model predictions are
reasonable.''
(Exhibit 12 at 7). See, e.g., 57 FR 33244 (July 27, 1992) (Studies
cited by NRDC do not provide a basis for the hearing because they
``support the [FDA] conclusion in question.'').
Second, this objection is premised on inaccurate factual statements
that are directly contradicted by the record. For example, the
objection disregards the fact that EPA scaled the PGW modeling to
reflect the lower current use rates. The Petitioners present no
challenge to the methods EPA used to scale the study results; indeed,
it is likely that their contractor used the same or similar
methodology. Equally, the objection that EPA relied on ``historical
monitoring data from a period when carbofuran use was an order of
magnitude larger'' is simply incorrect (Ref. Obj at 40). The monitoring
results EPA cited in the final rule were from the 1980s, but the
targeted monitoring studies were conducted with the same or lower use
rates as those permitted under the current labeling (74 FR 23085, May
15, 2009). Such a submission is insufficient to justify a hearing (See,
73 FR 42696 (July 23, 2008)(denying hearing where objector incorrectly
claimed that EPA had failed to rely on DDVP-specific information in
making its children's safety factor determination); 57 FR 6667
(February 27, 1992) (``A hearing must be based on reliable evidence,
not on mere allegations or on information that is inaccurate and
contradicted by the record.'')
Further, the Petitioners' misrepresentation of EPA's analyses also
affects the materiality of the hearing request (40 CFR 178.32(b)(3)).
Even if Petitioners were able to successfully refute the validity of
the PGW study, it would not affect the validity of the additional
monitoring data cited in the final rule (74 FR 23079 (May 15, 2009)),
on which EPA also relied to validate its monitoring. See, 49 FR 6672
(February 22, 1984) (challenge to one of five related studies; in the
absence of any additional data bearing on the clinical study, the
objection constitutes nothing more than an allegation).
Finally, the evidentiary proffered with respect to the Petitioners'
allegation that all areas with conditions similar to those found in the
PGW have been removed from the label is insufficient to warrant a
hearing (40 CFR 178.32(b)(2)). To the extent this allegation is based
on the information presented as part of the 2008 comments, this claim
was rebutted in EPA's final rule, by the modeling based on the
Wisconsin corn scenario, and by the lack of any underlying analyses to
support of Petitioners' comments. As explained in the final rule, the
information provided is insufficient to allow EPA to confirm the
Petitioners' contention that there is no overlap between use and all
potentially vulnerable ground water (74 FR 23061-23062 (May 15, 2009)).
The evidence submitted along with this objection does not cure this
defect. The only evidence proffered in this regard is the Petitioners'
comments on
[[Page 59653]]
the proposed rule, and the new analysis submitted in Exhibit 12. As
previously discussed, mere reiteration of comments made in response to
the proposed rule does not provide an adequate basis for a hearing,
unless the objector proffers some evidence calling EPA's conclusion
into question. Consequently, Petitioners' submission on this issue is
irrelevant and therefore immaterial, with regard to EPA's final
tolerance revocation (40 CFR 178.32(b)(3)). The analysis in Exhibit 12
appears to be the National Leaching Assessment described in
Petitioners' comments, but modified to account for the proposed
amendments submitted as part of the objections. As noted previously,
neither the National Leaching Assessment nor the model on which it was
based was submitted as part of the comments. Because the National
Leaching Assessment was available during the comment period but was
withheld, this information is considered to be untimely and the
Petitioners have waived the right to rely on it. For the reasons
discussed in Unit VI.D, EPA therefore will not consider it as an
appropriate basis for justifying a hearing on its final rule. See 73 FR
42683, 42696 (July 23, 2008); 72 FR 39318, 39324 (July 18, 2007).
Further, for the reasons discussed in Unit VI.C, EPA has determined
that objections and hearing requests based on the newly proposed
amendments, as well as evidence or analyses premised on those
amendments, are irrelevant, and therefore immaterial, to EPA's
determination in the May 15, 2009 final rule that the carbofuran
tolerances were unsafe and could not be sustained under FFDCA section
408. Petitioners are actually not objecting to the conclusions in EPA's
final rule; rather, they are suggesting that EPA might reach a
different result in a different factual scenario. Objections, however,
must be directed ``with particularity [at] the provisions of the
regulation or order deemed objectionable'' (21 U.S.C. 346a(g)(2)).
iii. Denial of objection. EPA denies this objection on several
bases. Based on the information available, and even accounting for the
September 2008 geographic restrictions, the Agency cannot confirm the
Petitioners' claim that use has been prohibited in all areas with
conditions similar to the PGW study. Based on the information that was
timely submitted, the only information provided was in map format.
While maps are useful for interpreting results, maps alone are
insufficient for a thorough evaluation of the Petitioners' claim, in
part because of the maps' spatial resolution. The maps submitted were
all on a nation-wide scale, which does not provide the level of detail
necessary to verify the combination of paramaters (e.g., soil textures,
pH) at locations identified as vulnerable. Further, the maps provided
by the Petitioner do not represent all carbofuran use patterns. For
example, Figure IV-2 on page 42 of the Petitioners' comments does not
address the granular use patterns and proposed label prohibitions. In
addition, as a general matter, none of the previously submitted
assessments provided a comprehensive analysis of the distribution of
soil and water pHs for the Midwest, Northwest or any other region of
the country where carbofuran use would be permitted on the September
2008 label, or have the Petitioners provided such an analysis with
their objections.
Further, the available scientific information does not support
their contentions. EPA examined readily available data with respect to
ground water and soil pH in order to evaluate the spatial variability
of pH. Data from the USGS and other readily available sources do not
necessarily encompass the entire range of ground water pH values
present within a state. This is especially true for shallow ground
water systems, where local conditions can greatly affect the quality
and characteristics of the water. Also, pH in a water body can be
higher or lower than the tabulated average values. In addition, average
ground water pH values for a given area do not truly characterize the
area's temporal and especially spatial heterogeneity. This can be seen
by comparing differences in pH values between counties within a state,
and by the fact that even within a county individual wells will
consistently yield ground water with either above- or below-average pH
values for that county. The ground water simulations in Reference 84,
Appendix I reflect variability in pH by modeling carbofuran leaching in
four different soil and subsurface pH conditions (pH 5.25, 6.5, 7.0,
and 8.7), representing the range in the aquifer system in that area.
This range also approximates the pH range of natural waters in general.
The results of the ground water simulations for corn use showed that a
relatively small (0.5) decrease in pH from 7 to 6.5 resulted in an
increase in the 1-in-10-year peak concentrations of carbofuran in
ground water of 4 orders of magnitude.
The results of EPA's revised corn modeling, based on a new scenario
in Wisconsin, are consistent with the results of the PGW study
developed by the registrant in Maryland in the early 1980s. Using
higher use rates than currently permitted, the peak concentration
measured in the PGW study was 65 ppb; when scaled to current use rates,
the estimated peak concentration was 11 ppb. EPA's modeling is also
consistent with a number of other targeted ground water studies
conducted in the 1980s showing that high concentrations of carbofuran
can occur in vulnerable areas; the results of these studies as well as
the PGW study are summarized in References 13 and 67. For example, a
study in Manitoba, Canada assessed the movement of carbofuran into tile
drains and ground water from the application of liquid carbofuran to
potato and corn fields. The application rates ranged between 0.44-0.58
pounds a.i./acre, and the soils at the site included fine sand, loamy
fine sand, and silt loam, with pH ranging between 6.5-8.3.
Concentrations of carbofuran in ground water samples ranged between 0
(non-detect) and 158 ppb, with a mean of 40 ppb (Refs. 13 and 67).
Finally, as discussed above, to the extent this objection relies on
untimely information and analyses, and on the newly submitted
registration amendments, the objection is denied as irrelevant and
immaterial.
b. Objection/hearing request subissue: Accounting for FMC's label
mitigation measures. Petitioners object that EPA's risk assessment
relies on ``unrealistic and overly conservative assumptions about
potential concentrations,'' and fails to account for FMC's label
mitigation measures. They claim that maximum concentrations of
carbofuran in groundwater are expected to be below 1.1 ppb, based on
the new proposed geographic restrictions and well setbacks. They allege
that, ``only permeable soils (e.g., greater than 90% sand and less than
1% organic matter) with acidic soils and water conditions, and shallow
water tables (e.g., less than 30 feet) are vulnerable to carbofuran
applications.'' They also claim that vulnerable groundwater only exists
along eastern seaboard, and in select counties in the United States,
where use has already been prohibited. They argue that further
confirmation is provided by the available NAWQA data, which show that
detections of carbofuran are rare, and occur only at low levels except
in areas where use is now prohibited. Finally, Petitioners allege that
in the specific regions where carbofuran will continue to be used under
the revised label, groundwater pH data collected under the USGS NAWQA
program demonstrate that the average pH is approximately 7.25, and in
most regions, moving two standard deviations
[[Page 59654]]
away from average, which they claim would capture 95% of all observed
values, results in pHs that are still greater than 6.0. According to
the Petitioners, under such conditions the combination of hydrolysis
and drinking water well setbacks would ensure that any carbofuran that
might reach ground water sources would degrade to only de minimis
concentrations less than or equal to 1.1 ppb.
In support of this objection, Petitioners cite the analyses
submitted as part of their comments, and the new analyses in Exhibits
12, 13, and 14. Exhibits 12 and 13 contain the revised modeling of the
estimated groundwater concentrations from carbofuran use, based on the
label restrictions proposed as part of the objections. Exhibit 14
consists of a statistical summary of groundwater pH statistics from the
USGS NAWQA database. Means, standard deviations, and numbers of
groundwater measurements in the database are summarized by state and
land use within each state.
i. Background. In the proposed rule EPA concluded that drinking
water taken from shallow wells is highly vulnerable to contamination in
areas where carbofuran is used around sandy, acidic soil, although
sites that are less vulnerable (e.g., deeper groundwater, less coarsely
textured soils) could still be prone to have concentrations exceeding
acceptable exposures (73 FR 44881-44883 (July 31, 2008)). EPA also
described the available NAWQA monitoring data, and explained the
reasons that the monitoring data tends to underestimate exposure for
acute risks, such as those carbofuran presents, and so are not
sufficiently robust to be used as an input into a quantitative risk
assessment or to serve as a lower bound (73 FR 44880-44881 (July 31,
2008)).
As part of their comments on the proposed rule, FMC requested that
EPA amend their registration to include a number of geographic use
restrictions and migitation measures intended to address the risks to
groundwater. In their comments, Petitioners claimed that
``[g]roundwater sources are vulnerable to carbofuran leaching only
under certain conditions, namely where permeable soils (e.g., areas
with soils greater than 90% sand and less than 1% organic matter),
acidic soil and water conditions, and shallow water tables predominate
(e.g., where ground water is less than 30 feet).'' The commenters
claimed that these conditions are rare in areas where carbofuran would
be used under the new label proposed as part of their comments. They
further asserted that in ``most states where carbofuran is used, less
than 2% of the entire surface areas possess sandy soil texture'' and
that ``low pH conditions are not found in carbofuran use areas allowed
under the registrant's amended label'' (Ref. 18 at 33-34). They
described, but did not submit analyses they claimed to have conducted
to demonstrate this. The summary consisted primarily of maps depicting
areas identified as vulnerable.
On December 24, 2008, FMC again requested that EPA amend their
registration to include additional restrictions intended to further
mitigate carbofuran's risks to groundwater.
In response to the September 2008 proposed label restrictions
submitted as part of the comments, EPA revised its risk assessment to
take into account the new geographic restrictions, as well as the
proposed risk mitigation measures. Based on its revised assessment, EPA
explained in the final rule that it disagreed that the criteria on the
September 2008 label defined 100% of the conditions where ground water
sources would be vulnerable to carbofuran leaching. EPA noted that no
comprehensive analysis had been provided that evaluated how the
Petitioners had reached this conclusion. As discussed in greater detail
in EPA's Response to Comments, the information provided as part of the
Petitioners' comments--primarily maps depicting areas identified as
vulnerable--was not sufficient to allow the Agency to evaluate their
claim (Ref. 84).
EPA also disagreed that the commenters provided sufficient
information to support their general claim that only high pH conditions
(pH above 7) existed in all the areas in which carbofuran could be used
under FMC's September 2008 revised label. EPA presented its assessment
of the newly submitted label in its Response to Comments document and
these issues were addressed in substantial detail there (Ref. 84).
EPA did not evaluate the mitigation measures proposed in the
December 24, 2008 submission. The mitigation measures in that
submission were incorporated into the measures proposed by the
Petitioners as part of their objections on June 30, 2009.
ii. Denial of hearing request. EPA is denying the hearing requested
on this objection because, in large measure, if not entirely, it rests
on the newly submitted mitigation measures accompanying Petitioners'
objections. As discussed in Unit VI.C, EPA has determined that these
objections do not warrant a hearing because they are irrelevant, and
therefore immaterial, to EPA's determination in the May 15, 2009 final
rule that the carbofuran tolerances were unsafe and could not be
sustained under FFDCA section 408 (40 CFR 178.32(b)(3)). Petitioners
are actually not objecting to the conclusions in EPA's final rule;
rather, they are suggesting that EPA might reach a different result in
a different factual scenario. Objections, however, must be directed
``with particularity [at] the provisions of the regulation or order
deemed objectionable'' (21 U.S.C. 346a(g)(2)). In addition, for the
reasons discussed in Unit VI.D, EPA has determined that the new risk
mitigation measures are not appropriately considered at this stage of
the administrative process, and will not grant a hearing on this basis.
Petitioners' objections provide no further clarification as to what
is meant by their claim that EPA's assessment relied on ``unrealistic
and overly conservative assumptions.'' Therefore, this objection, and
the attendant hearing request, is denied based on Petitioners' failure
to state with ``particularity * * * the basis for the objection * * *''
(40 CFR 178.25(a)(2)). As Petitioners raised similar allegations in
their comments, EPA has assumed that they intended to incorporate all
of the issues raised in the comments on the proposed rule.
To the extent this objection relies on the September 2008
mitigation measures, EPA denies the hearing request because the
evidentiary proffer in support of this objection is insufficient to
warrant a hearing. The record is clear on its face that EPA did account
for the mitigation measures in its revised risk assessment supporting
the final rule. A hearing can only be based on a genuine issue of
disputed fact (40 CFR 178.32(b)(1)). Where a party's factual
allegations are contradicted by the record, there is no genuine dispute
(73 FR 42701-42702 (July 23, 2008) (Denying NRDC's hearing request
where EPA had revised its residential exposure assessment to address
the issue complained of); 57 FR 6667, 6668 (February 27, 1992) (``A
hearing must be based on reliable evidence, not on mere allegations or
on information that is inaccurate and contradicted by the record.'')).
The objection also suffers from a further defect; many of the
allegations in this objection merely reiterate points Petitioners had
raised in their earlier comments. For example, EPA addressed the claim
that the NAWQA data from 1993-2006 rarely show detections of
carbofuran, and that in ``almost every instance'' the observed
concentrations are low. EPA also addressed the claim that only areas
with permeable soils (e.g., areas with soils greater than 90% sand and
less than 1% organic matter), acidic soil and water conditions, and
[[Page 59655]]
where shallow water tables predominate (e.g., where ground water is
less than 30 feet) present significant risks of leaching. As previously
discussed, mere reiteration of comments made in response to the
proposed rule does not provide an adequate basis for a hearing, unless
the objector proffers some evidence calling EPA's conclusion into
question (40 CFR 178.32(b)(3)). See, e.g, 73 FR 42701-42702 (July 23,
2008); 53 FR 53176 (December 30, 1988).
The evidence submitted in Exhibits 12-14 does not cure these
defects. As a preliminary matter, much of this evidence is untimely.
The analyses in Exhibits 12 and 13 appear to be the National Leaching
Assessment described in Petitioners' comments, but modified to account
for the proposed amendments submitted as part of the objections. As
noted previously, neither the National Leaching Assessment nor the
model on which it was based was submitted as part of the comments.
Certainly, there is no justification for Petitioners' refusal to
provide the analyses that were available during the comment period.
Because the National Leaching Assessment was available during the
comment period but was withheld, this information is considered to be
untimely and the Petitioners have waived the right to rely on it.
Accordingly, as discussed in Unit VI.D, because this evidence was not
presented as part of the Petitioners' comments, EPA considers that the
evidence submitted in support of this objection is not appropriately
considered as a basis for justifying a hearing on the final rule. See
73 FR 42683, 42696 (July 23, 2008); 72 FR 39318, 39324 (July 18, 2007).
And in the absence of this evidence, this portion of the objection
consists of mere allegations and denials, which do not warrant a
hearing (40 CFR 178.32(b)(2)).
But even assuming that the evidence was appropriately considered,
the evidence is insufficient, even if established, to justify the
factual determination urged (40 CFR 178.32(b)(3)). Nothing in Exhibits
12-13 provides any information that substantively differs from the
information summarized in the comments. Second, even assuming that the
analysis in Exhibit 14 is valid, on its face the submission states that
the analysis only addresses 95% of the samples chosen by the study; no
information was provided to explain how the samples relate to the state
or other geographic area in which carbofuran would be used. This is
important because NAWQA samples were not evenly distributed across most
states, but tended to be concentrated in particular regions; in
statistical parlance, the samples were not collected randomly. The maps
in Exhibit 14 clearly demonstrate that the study samples were not
randomly distributed across the state but were primarily in the
southern and eastern portions of each state, even though carbofuran use
is not restricted to those portions of the states. In other words, no
evidence was provided that would allow the Agency to determine the
percentage of the carbofuran use area represented by the 95% of the
samples the Petitioners' analysis addressed. Nor was any information
provided to document the significance of the remaining 5% of the
samples that were not captured by their analysis; for example, although
this may have only represented 5% of the samples, it is not clear
whether this 5% relates to only 5% of the areas where carbofuran may be
used, or whether it actually represent a far greater percentage of the
use area.
iii. Denial of objection. EPA denies this objection on several
bases.
The contention that the NAWQA monitoring data--or indeed any
available carbofuran monitoring data--provide an adequate basis for
concluding that concentrations will remain low in the areas where use
is now permitted is incorrect. The NAWQA program focuses on ambient
water rather than on drinking water sources, is not specifically
targeted to the high use area of any specific pesticide, and is sampled
at a frequency (generally weekly or bi-weekly during the use season)
insufficient to provide reliable estimates of peak pesticide
concentrations in surface water. For example, significant fractions of
the data may not be relevant to assessing exposure from carbofuran use,
as there may be no use in the basin above the monitoring site. Unless
ancillary usage data are available to determine the amount and timing
of the pesticide applied, it is difficult to determine whether non-
detections of carbofuran were due to a low tendency to move to water or
from a lack of use in the basin. As a consequence, the data do not
support relying on the non-detections as a lower bound, or relying on
the detections as an upper bound. The program, rather, provides a good
understanding on a national level of the occurrence of pesticides in
flowing water bodies that can be useful for screening assessments of
potential drinking water sources, especially for those assessments
concerned with chronic, rather than acute toxicants.
While there have been additional groundwater monitoring studies
that included carbofuran as an analyte, there has been no additional
monitoring targeted to carbofuran use in areas where aquifers are
vulnerable, and the locations of sampling and the sampling frequencies
generally are not sufficient to capture peak concentrations of the
pesticide in a watershed or aquifer where carbofuran is used. Capturing
these peak concentrations is particularly important for assessing risks
from carbofuran because the toxicity end-point of concern results from
single-day exposure (acute effects). Pesticide concentrations in ground
water are generally the result of longer-term processes and less
frequent sampling can often adequately characterize peak ground water
concentrations. However, such data must be targeted at vulnerable
aquifers in locations where carbofuran applications are documented in
order to capture peak concentrations. As a consequence, monitoring data
tends to underestimate exposure for acute endpoints.
EPA also disagrees that the Petitioners' criteria of soils composed
of 90% sand and less than 1% organic matter, and wells of less than 30
feet define all of the conditions under which ground water sources are
vulnerable to carbofuran leaching. No comprehensive analysis was
provided evaluating how they reached this conclusion. Although the
Petitioners proposed these criteria as restrictions on the carbofuran
label, the spatial extent of the label restrictions was not provided.
Moreover, as discussed in greater detail in EPA's Response to Comments,
the information provided as part of the Petitioners' comments
(primarily maps depicting areas identified as vulnerable) was not
sufficient to allow the Agency to evaluate their claim (Ref. 84). For
example, the percent sand, one of the criteria used in this analysis,
varies significantly across a field and the whole range of soil
textures may occur at a county-level. The national map provided
purports to represent this parameter and several others aggregated
together to identify vulnerable locations. This national-scale map does
not provide the level of detail needed to verify the combination of
paramters at locations identified as vulnerable.
While the assertion that soils with 90 percent sand are the most
vulnerable to leaching is in part true, it is misleading. While many
states have only small areas of sandy soils, several of the states in
which carbofuran would continue to be used under the Petitioners'
proposals have quite extensive areas. For example, according to the
Petitioners' own assessment of states with high amounts of carbofuran
application (Ref. 6), Texas had 4.2% of soils classified ``as sand'',
Michigan had 21.3% and Nebraska had
[[Page 59656]]
26.3%. In addition, the Petitioners' statements imply that soils that
are sandy textured define the universe of soil textures that are
vulnerable to leaching. It is possible that more fine-textured soils,
for example sandy loams or silt loams, could also be sufficiently
permeable to result in carbofuran leaching as it has not been
established how much of a reduction in leaching might occur as texture
becomes finer. Furthermore, finer textured soils tend to have more
cracks and root channels and thus are more prone to preferential flow.
Petitioners' claims regarding pH concentrations are also incorrect.
As an initial matter, their analysis fails to prove that pH values in
all use areas will ensure that concentrations are below the level of
concern because the analysis in Exhibit 14 is based on a flawed
statistical analysis. The methodology on which the Petitioners relied--
the use of the mean minus two standard deviations--to estimate the 5th
percentile (i.e., 95% of the samples above the value) of the
distribution of ground water pHs in a state depends strongly on the
shape of the distribution. This method relies on three assumptions: 1)
That the data is randomly sampled, 2) that the samples are normally
distributed (i.e., a bell-shaped distribution), and 3) that the samples
are independent (i.e., the sampling locations do not share common
characteristics and are not clustered). The maps in Exhibit 14 clearly
demonstrate that the study samples were not randomly collected across
each state but were primarily in the southern and eastern portions of
the states, even though carbofuran use is not restricted to those
portions of the states. For example, Figure 1 in Exhibit 14 clearly
shows that the vast majority of the wells sampled in North Dakota and
South Dakota are in the eastern half of the state, and in Nebraska in
the southern and eastern parts. Therefore the wells sampled will not be
representative of the full distribution of wells in the state. On the
second assumption, the analysis provided by the Petitioners did not
determine whether the distribution was normal; the accuracy of
percentiles at the tails of the distribution, such as the 95th
percentile, are very sensitive to the accuracy of this assumption.
Environmental data are usually not normally distributed; log-normal
distribution is more typical (Ref. 60). If the shape of the
distribution is not known, a non-parametric or `empirical' estimation
of the percentiles is better because it does not depend on the same
assumption of normal distribution. Finally, the pH in various wells may
or may not be statistically independent. Samples taken across the
landscape are usually spatially correlated up to a certain distance.
Beyond that distance, they are statistically independent.
Unfortunately, this was not determined as part of this analysis. While
pH is clustered across the state, there is considerable spatial
variability in pH conditions for both the subsurface and surface
environments. This is especially true for shallow ground water systems,
where local conditions can greatly affect the quality and
characteristics of the water. This can be seen by comparing differences
in pH values between counties within a state, and noting that even
within a county individual wells will consistently yield ground water
with either above- or below-average pH values for that county.
Furthermore, even if the statistical calculations was correct, by
definition this evidence would not support a determination that
groundwater concentrations would never exceed 1.1 ppb, as 5 percent of
the samples would result in concentrations that are higher.
In conducting its modeling for the final rule, EPA examined readily
available data with respect to ground water and soil pH to evaluate the
spatial variability of pH in Wisconsin. As part of the final rule, EPA
explained that ground water pH values can span a wide range; this is
especially true for shallow ground water systems, where local
conditions can greatly affect the quality and characteristics of the
water (higher or lower pHs compared to average values). As noted even
within counties in the same state, wells will consistently yield ground
water with either above- or below-average pH values for that county.
Thus, EPA concluded that average ground water pH values for a given
area do not truly characterize the (temporal and especially spatial)
heterogeneity common in most areas. The actual significance of using a
single pH even if it is a 95th percentile value, which as described
above was not demonstrated to be accurately calculated, is not clear.
For this reason, EPA bracketed potential exposure using a range of pH
values.
As further explained in the final rule, the considerable spatial
variability in pH conditions for both the subsurface and surface
environments is significant because the pH has a large effect on the
persistence of carbofuran. This is demonstrated by the results of the
ground water modeling simulations from the South-Central Wisconsin
scenario, which show that what might appear as relatively small
variations in soil pH can have a significant impact on estimates of
carbofuran in ground water. Under more acidic conditions, the
hydrolysis half-life increases from 28 days at pH 7 to years or more at
pHs less than 6. Further, the results of EPA's corn ground water
simulations (bounded by the high and low pH values of the aquifer
system underlying the scenario location) showed that a relatively small
(0.5) decrease in pH from 7 to 6.5 resulted in an increase by 4 orders
of magnitude in the 1-in-10-year peak concentration of carbofuran.
The ground water simulations reflect variability in pH by modeling
carbofuran leaching in four different pH conditions (pH 5.25, 6.5, 7.0,
and 8.7), representing the range in the Wisconsin aquifer system. The
upper and lower bound of pH values that EPA chose for this assessment
were measured values from the aquifer, and the remaining two values
were chosen to reflect common pH values between the measured values.
Estimated 1-in-10-year peak ground water concentrations at pH 7 are
1.6x10-3 ppb; however, the estimated 1-in-10-year peak
ground water concentration at pH 6.5 is 16 ppb, nearly 4 orders of
magnitude greater. EPA explained that, because of carbofuran's
sensitivity to pH, the Agency had concerns that any given set of
mitigation measures would not successfully protect groundwater source
drinking. Data indicate that pH varies across an agricultural field,
and also with depth (Ref. 49). In particular, the pH can be different
in groundwater than in the overlying soil. The upper bound of the
carbofuran concentrations estimated by EPA at pH 6.5 is much greater
than the concentrations the Petitioners reported in their objections.
EPA's complete assessment of the 2008 revised label can be found in its
Response to Comments document and these issues were addressed in more
detail there (Ref. 84).
For all of these reasons, the objection is therefore denied.
c. Objection/hearing request subissue: Consistency with groundwater
concentration in NMC-CRA. Petitioners object that EPA's estimates in
the final rule are inconsistent with the groundwater concentration
estimates EPA developed for the NMC (CRA). However, they do not
identify any specific inconsistency, they simply make the general
allegation. They allege that, by contrast, their assessment, which
estimated maximum concentrations of 1.1 ppb, is consistent with the NMC
CRA.
i. Background. The NMC CRA examined carbofuran at two sites,
northeastern Florida and the Delmarva Peninsula. In Florida,
concentrations
[[Page 59657]]
were found to be below levels of concern because of high pH, but in
Delmarva, both in corn and in melon scenarios EPA estimated that 90% of
daily concentrations could be as high as 20.5 and 25.6 ppb,
respectively. In the proposed and final rules, EPA cited the modeling
conducted for the NMC to support its estimates. In addition, EPA used
the same methodology used to develop the estimates for the NMC CRA, to
conduct the modeling for the additional crops and locations on which
carbofuran use occurs.
Although the Petitioners alleged that their estimates were
consistent with the NMC CRA in their comments on the proposed rule,
they did not identify any specific inconsistency between EPA's
groundwater estimates for the proposed rule and its estimates for the
NMC CRA.
ii. Denial of hearing request. EPA denies the request for a hearing
on this subissue because there is no disputed factual matter for
resolution. There is no dispute as to the methodology EPA used to
conduct its modeling in either assessment. Petitioners have not
identified any specific inconsistency between EPA's groundwater
exposure assessment conducted for this rule and the assessment
conducted for the NMC CRA. Instead, they rely on mere allegations and
denials. As EPA's regulations make clear, a mere ``denial'' of an EPA
position is not sufficient to satisfy the standard for granting a
hearing (40 CFR 178.32(b)(2)). Moreover the question of whether EPA's
assessments are consistent requires the application of a legal standard
to undisputed facts, and is thus a legal or policy question. Hearings
are not appropriate on questions of law or policy (40 CFR
178.32(b)(1)). (73 FR 42696-42697) (denying a hearing on EPA's decision
to reduce the children's safety factor, in the absence of data from the
endocrine screening program, on the ground that the objection
constituted a legal issue). FDA has repeatedly confirmed that the
application of a legal standard to undisputed facts is a question of
law for which a hearing is not required. (See, e.g., 68 FR 46403, 46406
n.18, 46408, 46409 (August 5, 2003) (whether facts in the record show
there is a reasonable certainty of no harm is a question of law;
whether a particular effect is a ``harm'' is a question of law)).
Neither does the claim that their modeling is consistent with the
NMC CRA justify a hearing on this question. As EPA explained in the
final rule, the values estimated in the modeling conducted for the NMC
CRA are greater than the 1 ppb that FMC claims is the maximum expected
1-in-10-year peak concentration. A hearing is not warranted where the
claim is clearly contradicted by the record (40 CFR 178.32(b)(2)). See,
e.g., 57 FR 6667 (February 27,1992) (``A hearing must be based on
reliable evidence, not on mere allegations or on information that is
inaccurate and contradicted by the record.''); 49 FR 6672 (February 22,
1984) (hearing denied where claim was based on demonstrably false
premise).
iii. Denial of objection. As discussed in the final rule and
response to comments document, the Petitioners' results are not
consistent with the estimates developed for the NMC CRA. The NMC CRA
examined carbofuran at two sites, northeast Florida and the Delmarva
Peninsula. In Florida, concentrations were found to be below levels of
concern because of high pH, but in Delmarva, both in corn and in melon
scenarios EPA estimated that 90% of daily concentrations could be as
high as 20.5 and 25.6 ppb, respectively. These values are greater than
the 1 ppb that Petitioners claim is the maximum expected 1-in-10-year
peak concentration.
2. Objections relating to surface water exposure estimates--a.
Objection/hearing request subissue: Use of percent of the crop treated
(PCT) in surface water modeling. The Petitioners object to the
assumption in the surface water assessments in the final rule that 100%
of the crops in a watershed will be treated with carbofuran. The
Petitioners argue that actual carbofuran sales data on a county basis
from 2002-present demonstrate that the current carbofuran PCT is less
than 4.25%. Using this PCT, and taking into account the recently
submitted ``no application buffers,'' the Petitioners allege that the
modeling in Exhibit 15 demonstrates that carbofuran concentrations in
surface water will not exceed 1.1 ppb, ``which is below the level of
concern.''
In support of this objection, the Petitioners reference county
level sales data that were submitted to the Agency on November 7, 2008,
after the close of the comment period. They also reference the use
tracking system proposed in their recent registration amendments
(Exhibit 2) and the modeling contained in Exhibit 15.
i. Background. To conduct an assessment of a pesticide's potential
to contaminate surface water, EPA estimates the percentage of farmland
in a watershed on which a particular crop is grown (e.g, corn); this is
referred to as the percent cropped area (PCA). EPA then assumes that
100% of the cropped area is treated with the pesticide that is the
subject of the assessment. In the proposed rule, EPA explained that the
reason for its assumption that 100% of PCA in a watershed is treated is
due to the large uncertainties in the actual PCT on a watershed-by-
watershed basis. EPA developed an extensive discussion of the
uncertainties in PCT and how they impact drinking water exposure
assessment in its proposed rule (73 FR 44885 (July 31, 2008)), and in a
background document previously provided to the SAP considering the
draft carbofuran NOIC (Ref. 45). The data are generally not available
on the scale necessary to allow for reliable estimates of pesticide use
in a watershed. Such data are generally available only on a statewide
basis, and if such estimates are used to account for PCT, it will
underestimate the risks for some drinking water facilities in the
state, as these estimates represent only a state-wide average. In some
cases this underestimate can be substantial, because usage may not be
evenly distributed across the landscape; due to differences in factors
like pest pressure, local consultant recommendations, and weather, it
may be much higher in some areas. Further, temporal uncertainties can
result in changes in use that might be driven by weather, changes in
insect resistance over time, and changes in agronomic practices. To
date, methods that account for this uncertainty, given the nature of
the available data, have not been developed. EPA explained that as a
consequence, the Agency could not accurately estimate a drinking-water
watershed scale PCT that, when used in a quantitative risk assessment
on a national or regional basis, standing alone, provides the necessary
level of certainty to allow the Agency to confidently conclude that
exposures will meet the FFDCA section 408 safety standard. EPA also
described the results of a sensitivity analysis conducted using a low
PCT estimate.
In their comments on the proposed rule, the Petitioners criticized
the Agency for this assumption, arguing that because carbofuran is used
on such a low percentage of crops nationally that it is unrealistic to
assume that such a large percentage of any individual watershed would
be treated. To support their claims that the PCT would generally be
below 4%, they referenced county-level ``use'' data, but failed to
provide either the data or methodology on which they relied until after
the close of the comment period.
In the final rule, EPA explained at length the reasons that the
information provided during the comment was insufficient to allow the
Agency to reliably estimate a lower PCT for carbofuran. EPA did not
review the information submitted after the close of
[[Page 59658]]
the comment period. However, based on the information that could be
gleaned from the description in the comments, EPA explained that the
data on which they relied did not appear to be ``use'' data, but sales
data, and that both the data and methodology failed to support the
claims made in the Petitioners' comments. The Agency also described the
results of a sensitivity analysis conducted to determine the impact
that PCT could have on the risk assessment, which demonstrated that
even assuming that a low percentage of a watershed is treated with
carbofuran, exposures will still be unsafe for infants.
ii. Denial of Hearing Request. To the extent Petitioners' objection
is limited to EPA's refusal to use a 4% PCT in estimating drinking
water concentrations, EPA has concluded that the objection does not
warrant a hearing because the Petitioners' objection on this subissue
is irrelevant, and therefore immaterial, with regard to EPA's final
tolerance revocation. The Petitioners have not responded to EPA's
explanation in the final rule of the reasons that the information and
methodology on which they relied to estimate a 4% PCT was flawed. As
discussed in the final rule, EPA had assumed that the data on which
they were relying was sales data, and so the resubmission of the
information sent in after the close of the comment period only confirms
that the Agency's analysis was correct; it does not rebut EPA's
substantive concern that such information is insufficient to support
the conclusions the Petitioners assert. In essence, the Petitioners
ignored EPA's extensive analysis of this issue in the final rule and
simply refiled their comments on the proposal as if EPA's determination
in the final rule did not exist. The statute, however, requires that
objections be filed on the final rule not the proposal. By ignoring
EPA's final rule on this issue, Petitioners have failed to lodge a
relevant objection. When an objector does not challenge EPA's
conclusions in the final rule, but merely reiterates comments made on
the proposed rule, without submitting some evidence that calls EPA
final rule conclusions into question, the objector has not raised a
live controversy as to an issue material to the final rule (See 73 FR
42698-42699 (July 23, 2008) (denying several NRDC hearing requests
because the objections were based on EPA's preliminary DDVP risk
assessment, rather than the revised risk assessment published with the
final order); 53 FR 53176, 53191 (December 30, 1988) (where FDA
responds to a comment in the final rule, repetition of the comment in
objections does not present a live controversy unless the objector
proffers some evidence calling FDA's conclusion into question)).
An additional flaw in this objection is that the proffered evidence
is untimely and insufficient. Neither the proposed registration
amendments nor the evidence submitted as part of this objection,
including the modeling in Exhibit 15, was provided to the Agency during
the comment period. The modeling in Exhibit 15 was available, because
it was summarized in Petitioners' comments; however the underlying
modeling was withheld. Equally, there is no evident reason that the
sales data could not have been submitted as part of the Petitioners'
comments. Petitioners relied on this data to perform analyses completed
in 2006-2007, for purposes of the January 2008 SAP review of the draft
carbofuran NOIC, so the information was available long before their
comments needed to be filed. Accordingly, as discussed in Unit VI.D,
this information is not appropriately considered as a basis for
justifying a hearing on its final rule. Moreover, as explained below,
because no evidence was submitted in support of the newly proposed use
tracking system, reliance on that proposal to support a low PCT
constitutes nothing more than an allegation. This is not an adequate
basis on which to grant a hearing (40 CFR 178.32(b)(2)). Finally, to
the extent this objection relies on Petitioners' recently proposed risk
mitigation measures, as discussed in Units VI.C and D, objections and
hearing requests based on these new risk mitigation measures are not
appropriately considered at this stage of the administrative process,
and are denied as immaterial (40 CFR 178.32(b)(3)).
iii. Denial of objection. While the Agency typically uses PCT in
developing estimates of pesticide residues in food, this is entirely
different than developing estimates of the percent of a watershed that
is treated for purposes of estimating drinking water exposures. Food is
generally randomly distributed for sale across the nation without
regard to where it is grown. This tends to even out any PCT variations
that may arise on local levels. By contrast, the source of water
consumption (and consequently exposure) is localized, either in a
private well or a community water system. The PCT in any watershed will
therefore directly impact the residues to which people living in that
watershed will be exposed.
For this reason, among others, for drinking water exposure
estimation, the Agency assumes that 100% of the cropped area (or 100%
PCT) is treated with the pesticide. EPA also makes this assumption due
to the large uncertainties in the actual PCT on a watershed-by-
watershed basis. EPA included an extensive discussion of the
uncertainties in PCT and how they impact drinking water exposure
assessment in its proposed rule (73 FR 44834) and in a background
document provided to the SAP considering the draft carbofuran NOIC
(Ref. 45). Because usage is often not evenly distributed across the
landscape, due to differences in factors like pest pressure, local
consultant recommendations and weather, it may be much higher in some
areas. Further, temporal uncertainties can result in changes in use
that might be driven by weather, changes in insect resistance over
time, and changes in agronomic practices. To date, methods that account
for this uncertainty, given the nature of the available data, have not
been developed. Consequently, EPA cannot accurately estimate a
drinking-water watershed scale PCT that, when used in a quantitative
risk assessment on a national or regional basis, standing alone,
provides the necessary level of certainty to allow the Agency to
confidently conclude that exposures will meet the FFDCA section 408
safety standard.
In most cases, EPA agrees that it is unlikely that 100% of the crop
will be treated with a single pesticide in most watersheds,
particularly in larger watersheds. However, for small watersheds, it is
reasonable to assume that an extremely high percentage of the crops in
the watershed may be treated.
Moreover, EPA has an obligation to evaluate all legally permitted
use practices under the label, and to ensure that all such use meets
the requisite statutory standards, not simply to base its decisions on
the practices the majority might typically use. The September 2008
proposed label, submitted during the comment period, imposes no
restriction on the application of carbofuran related to whether a
particular percent of the watershed has been treated. Thus, even with
the restrictions on FMC's September 2008 labels, it remains legally
permissible for 100% of the watershed to be treated with carbofuran.
Nor is EPA aware of an enforceable mechanism to ensure that farmers
applying pesticide to their individual fields will have the ability to
indendently determine whether a particular percentage of the watershed
has been treated. There are significant practical difficulties inherent
in implementing such label directions, as
[[Page 59659]]
they force individual growers to have continual knowledge of the
variances of the behavior of other farmers across the entire watershed.
While for small watersheds that involve only one or two farms it might
be feasible for neighbors to independently coordinate applications with
respect to adjacent fields, for larger watersheds or for smaller
watersheds with multiple farms, the practical difficulties increase
significantly. And as explained below in Unit VI.F.2.D, significant
questions remain regarding the efficacy of Petitioners' proposed use
tracking system.
However, in the final rule, EPA conducted a sensitivity analysis to
explore the impact of the PCT assumption on dietary risk using an
assumed 10% PCT, a figure proposed previously by FMC (74 FR 23065-
23066). The results of that analysis demonstrated that even at these
low percentages, which may significantly underestimate exposures,
particularly in small watersheds, carbofuran exposures from drinking
water contribute significantly to children's dietary risks. EPA
conducted a similar sensitivity analysis for the final rule, discussed
below in Unit VI.F.3, which demonstrates that even assuming that a low
percentage of a watershed is treated, exposures will still be unsafe
for infants.
Since EPA's 2006 determination that carbofuran does not meet the
safety standard, FMC has submitted three assessments that relied in
part on what they refer to as ``county-level usage data'' (Refs. 29,
74, and 89). Based on the information provided with the objections, the
original source of the ``county-level usage data'' is sales data,
apparently collected at the distributor level. The Petitioners claim to
have augmented these sales data in an unspecified manner, by
incorporating information from the distributors, which was used to
allocate carbofuran usage at the county level. In their comments on the
proposed rule, the Petitioners provided maps representing county level
and watershed-scale use estimates, but did not provide the actual usage
estimates in any clearly understandable format.
The Petitioners did submit these sales data as part of their
objections, but have provided only a limited description of how these
data were collected and no description of how they were actually
analyzed or validated; what was characterized as ``careful and proven
techniques to capture this data'' were not described. The method used
to attribute carbofuran sales to counties was not described. Nor have
they explained what is meant by negative usage estimates.
The Agency agrees that county-level use data would be useful in
generating reasonable estimates of PCT that might be appropriately used
in drinking water assessments. However, no usage data have been
provided. Rather, the Petitioners only provided county-level use
estimates for Illinois, although they have not submitted the analyses
that presumably are the basis for the estimates. County-level estimates
to support other risk assessments have not been submitted by the
Petitioners. Further, the Petitioners have provided limited
characterization of the source data, noting that these data were
derived from FMC billings and ``EDI data'', but they did not provide
either the billings or the EDI data, nor explain how they were
collected.
There are two major problems in equating sales information with use
information: (1) Mapping the point and time of sale to the point and
time of use and (2) allocating the amount sold across the crops on
which it can be used. The submission did not explain how either of
these two problems was resolved.
The first problem is highlighted by the fact that for some county/
crop/year combinations in the submitted tables, estimated usage is
negative. Use of a pesticide clearly cannot be negative, but sales at a
particular point and time can be negative because buyers can return
unused product. The fact that some usage estimates are negative
suggests that buyers are returning carbofuran product purchased in an
earlier time period or from another location. But if farmers are
returning carbofuran purchased in a previous time period, any
assessment must also account for the possibility that they also could
use stocks purchased previously. Thus, use in a given year may be
greater than sales in that year. Similarly, if farmers are returning
carbofuran purchased in another location, it must be recognized that
they could be using carbofuran purchased in another location. Thus, use
in any given county or watershed could be greater than sales in that
locality. That is, regardless of whether the issue is use over space,
time, or both, the results are that usage will be underestimated in
some localities. Further, zeroing out the negative values will not
result in appropriate estimates; the negative usage estimates merely
make the problem manifest. Even total sales at a point in time may
underestimate actual use.
The second problem arises with the allocation of product sales
across the crops on which it can be used. The data provided as part of
the objections were aggregated for all crops, including crops on which
use is no longer allowed, such as cotton or alfala; the data were not
collected based on the individual crops. No explanation is provided to
indicate how the Petitioners divided the quantity sold between the
amount used on cotton, on alfalfa, and on all other crops. Since part
of the purpose of the Petitioners' assessment is presumably to show
that eliminating the use on the cancelled crops, such as alfalfa, will
sufficiently reduce any risks, it is critical to know how they
determined the amount used on alfalfa as opposed to other crops, and it
is difficult to imagine how this could be done with any accuracy. For
example, one could assume that the chemical is used on equal proportion
of all crops, but there is no basis for such an assumption. It might
not matter if all EPA were interested in was the total amount used in
an area, but this is not useful for purposes of assessing the risk on a
smaller scale, such as in the present case.
The method the Petitioners used to generate use estimates from the
sales data does not account for the uncertainties described above nor
for the potential for use to be locally concentrated due to pest
pressures. The method that is summarily described as having been used
to allocate county-level usage estimates to watersheds appears to be
similar to a method that has been used by others to calculate ``best-
estimate'' county-level PCT (Ref. 73) to map nationwide pesticide
usage. However, these methods are not appropriate for calculating PCTs
for surface drinking water sources or watersheds that drain to
community water systems, because they do not adequately account for the
uncertainty in the data at the appropriate spatial scale. This
methodology produces an estimate that is a measure of central tendency
and, as such, roughly half the estimated values will underestimate the
PCT. Furthermore, because pesticide use varies from year to year, and
can in some cases be patchy, with high levels of use in small areas and
little use in most areas, the underestimates of PCT can be substantial
in small watersheds. As previously noted, methods for calculating PCT
that account for these uncertainties have not been developed.
Accordingly, EPA denies this objection.
b. Objection/hearing request subissue: Results of FMC modeling. The
Petitioners claim that the prior surface water assessments submitted to
the Agency demonstrated that carbofuran concentrations in surface water
were not expected to exceed 1.1 ppb. They claim
[[Page 59660]]
that these studies provide further confirmation of the results of the
new modeling conducted to support their objections, which also
concluded that concentrations would be less than 1.1 ppb. In support of
this objection, the Petitioners reference the previously submitted
studies, along with the modeling provided in Exhibit 15. The modeling
in Exhibit 15 appears to be the modeling that was originally summarized
in their comments, but that the Petitioners withheld. The modeling was
also supplemented to account for the newly proposed registration
amendments submitted as part of the objections.
i. Background. In their comments, the Petitioners alleged that the
results of their modeling showed that concentrations of carbofuran in
surface water would not exceed 1.1 ppb. The comments referenced two
surface water assessments that they had submitted to the Agency prior
to the proposed tolerance revocation: a surface water assessment based
on an Indiana Community Water System (CWS) (Refs. 89 and 90) and an
assessment based on the Watershed Regressions for Pesticides (WARP)
model. They also summarized additional surface water modeling that had
been conducted to support their comments on the proposed rule, a
Nationwide Community Water System Assessment (Ref. 57), but did not
submit the actual modeling, or identify or describe in detail the model
on which they relied.
In the final rule, EPA explained the flaws in all of the
Petitioners' assessments that caused the Agency to reject the studies'
conclusions. For the two assessments that had actually been submitted
to the Agency, EPA was able to definitively explain the flaws. With
respect to the Nationwide CWS modeling that was summarized in their
comments, EPA evaluated the modeling based on the information it was
able to glean from the description provided in the comment discussion.
ii. Denial of hearing request. A hearing is denied on this subissue
because EPA has concluded that Petitioners' objection on this issue is
irrelevant, and therefore immaterial, with regard to EPA's final
tolerance revocation regulation (40 CFR 178.32(b)(3)). In the final
rule, and in other rulemaking documents, EPA provided a detailed
explanation of the bases for its conclusions that the previously
submitted assessments were invalid (74 FR 23062-23064 (May 15, 2009)).
Petitioners have not challenged EPA's explanation, nor explained how
the resubmission of the same studies addressed the substantive issues
EPA raised. Because Petitioners ignored EPA's extensive analysis of
this issue in the final rule, they have essentially refiled their
comments on the proposal as if EPA's determination in the final rule
did not exist. The statute, however, requires that objections be filed
on the final rule, not on the proposal (21 U.S.C. 346a(g)(2)). By
ignoring the EPA's final rule on this subissue, Petitioners have failed
to lodge a relevant objection. Petitioners' resubmission of the exact
same information does nothing to call EPA's conclusion into question,
which is what is required to maintain their claim at this stage of the
proceeding. When an objector does not challenge EPA conclusions in the
final rule, but merely reiterates comments made on the proposed rule
without submitting some evidence that calls EPA final rule conclusions
into question, the objector has not raised a live controversy as to an
issue material to the final rule. (See 73 FR 42700-42701 (July 23,
2008) (hearing request denied where NRDC failed to challenge EPA's
conclusion that challenged study is consistent with several other
studies, but merely reiterated assertions from its original petition
that the study is not representative); 53 FR 53176, 53191 (December 30,
1988) (where FDA responds to a comment in the final rule, repetition of
the comment in objections does not present a live controversy unless
the objector proffers some evidence calling FDA's conclusion into
question)).
With respect to the modeling submitted in Exhibit 15, this evidence
is untimely. The modeling submitted in Exhibit 15 appears to be a
fuller description of Petitioners' National CWS Assessment, which was
described but not provided as part of their comments on the proposed
rule. The modeling also has been revised to account for the newly
proposed risk mitigation measures. However, even with the greater
detail provided, the information contained in Exhibit 15 still fails to
address many of the deficiencies EPA identified in the final rule. For
example, although some further detail has been provided of how the
Petitioners modeled the vegetated buffer strip, the complete
information EPA would need to assess the modeling was not provided; the
material provided is insufficient to understand how the simulations
were performed or how the simulations were parameterized. Nor have the
Petitioners submitted the inputs used in modeling estimated
concentration from spray drift. As discussed in Unit VI.D, because the
modeling in Exhibit 15 was not provided during the comment period, and
to the extent that the detailed information EPA identified as lacking
in the final rule has still not been provided, the evidence submitted
in Exhibit 15 is not appropriately considered as a basis for justifying
a hearing on its final rule. And in the absence of this evidence, this
objection consists of mere allegations and general denials, which are
inadequate to justify a hearing (40 CFR 178.32(b)(2)).
Further, to the extent that this objection relies on the ``no
application buffers,'' or the proposed use tracking system newly
submitted as part of their objections to support the models' assumption
of a low PCT, the hearing request is denied as irrelevant, and
therefore immaterial, to EPA's determination in the May 15, 2009 final
rule, for the reasons discussed in Unit VI.C. Petitioners are actually
not objecting to the conclusions in EPA's final rule; rather, they are
suggesting that EPA might reach a different result in a different
factual scenario. Objections, however, must be directed ``with
particularity [at] the provisions of the regulation or order deemed
objectionable'' (21 U.S.C. 346a(g)(2). And, as explained below, because
no evidence was submitted in support of the newly proposed use tracking
system, reliance on that proposal to support a low PCT constitutes
nothing more than an allegation. This is not an adequate basis on which
to grant a hearing (40 CFR 178.32(b)(2)).
iii. Denial of objection. To the extent this objection relies on
Petitioners' newly submitted registration amendments, the objection is
denied as immaterial. EPA also denies the remaining objections because,
based on its review of the submitted modeling, EPA has concluded all of
the modeling has substantial flaws that render the model results
invalid. EPA has previously reviewed these assessments, and provided a
detailed explanation of the reasons for the Agency's conclusions, most
recently, in the final rule and the associated response to comments (74
FR 23060-23064, Ref. 84). EPA's reasoning is summarized briefly below.
Indiana CWS Assessment
EPA has previously reviewed the Indiana surface water assessment,
and has provided comments on that submission (Ref. 45), many of which
were reiterated at length in the final rule and response to comments
documents (74 FR 23062-23064, Ref. 84). The Petitioners originally
submitted this study to demonstrate that ``EPA's standard index
reservoir scenario
[[Page 59661]]
overestimates surface water concentrations compared with expected
concentrations in actual Indiana CWS where carbofuran is used.'' The
Index Reservoir is designed to be used as a screen, and as such,
represents watersheds more vulnerable than most of those that support a
drinking water facility. It is thus protective of most drinking water
on a national basis. That, however, does not mean that EPA believes
this scenario overestimates concentrations for all drinking water
reservoirs. EPA agrees that it is an appropriate refinement to simulate
local and regional watersheds, and has in fact done so (Refs. 44, 46,
47, 48, and 84). However, for the reasons discussed below, EPA does not
believe that the Petitioners' assessment demonstrates that carbofuran
concentrations will not exceed 1.1 ppb in Indiana surface water sources
of drinking water. Even accepting the Indiana surface water assessment
at face value, the estimated 1-in-10-year peak concentrations at some
facilities were as high as 6.88 [micro]g/L, and these concentrations
substantially exceed the 1.1 ppb concentration the Petitioners now
claim represent reasonable estimates.
The study also fails to support the Petitioners' other conclusions.
The study was originally intended to demonstrate two points: (1) That
the vulnerability of the Indiana CWS ``brackets'' the Index Reservoir,
and (2) that the concentrations they estimated for these locations are
significantly less than EPA estimates. Regarding the vulnerability of
the CWS, the assessment describes their approach for modifying the
parameters of the Index Reservoir scenario to represent 15 reservoir-
based watersheds in Indiana cropped in corn. The study indicates the
Petitioners have included data that, based on EPA's review of these
submissions, are not available at the appropriate scale to determine
all site-specific parameters. The Petitioners modified some of the
parameters based on available data to represent more localized
conditions that are more or less vulnerable than for the Index
Reservoir. From the description, the Petitioners' approach is similar
to the methods that EPA uses to develop new scenarios, in that soil and
weather data are varied in order to represent different locations.
However, for other parameters, EPA believes the modifications are
inconsistent with fundamental assumptions upon which the modeling is
based. In previous submissions to the Agency, FMC has described that
they have made modifications to scenarios to reflect local conditions
of each CWS in Indiana by modifying the soil and weather data and
altering the ratio of watershed drainage area to the reservoir capacity
(Ref. 89). EPA agrees that soil and weather data can be modified to
reflect conditions at local watersheds. However, EPA disagrees that
altering the ratio of watershed drainage area to the reservoir capacity
(i.e., the DA/NC) is a reasonable modification.
The DA/NC parameter is associated with increased concentrations in
drinking water reservoirs to a certain point. The Petitioners adjusted
their EDWCs for each drinking water facility by a factor representing
the ratio of the DA/NC for each reservoir divided by the DA/NC for the
Index Reservoir (which is 12). EPA does not believe this is appropriate
for two reasons. First, the relationship between concentrations and the
DA/NC is not strictly linear. Small DA/NCs imply a small watershed
combined with a large reservoir. As the DA/NC increases, the relative
watershed size increases, and thus the runoff volume going into the
reservoir also increases. This is also means the reservoir's ability to
dilute the runoff decreases; the result is that concentrations increase
with an increase in the DA/NC. However, at some point, the runoff
volume exceeds the reservoir capacity, and rather than increasing the
pesticide concentration, the excess runoff flows out of the reservoir,
carrying the pesticide with it. Thus, because pesticide concentrations
are not linearly related to the DA/NC, it is not appropriate to
multiply the model output by a linear DA/NC adjustment factor.
Secondly, the PRZM model, which is used to simulate the watershed for
the Index Reservoir, is a field-scale model. As the watershed size (and
the DA/NC) increases, assumptions upon which PRZM relies (namely:
uniformity of soils, equal and simultaneous movement of runoff to the
reservoir, and uniform weather across the watershed) no longer hold and
the model becomes less valid for simulating the runoff processes. The
geometry of the Index Reservoir was chosen partly to avoid these two
limitations (Ref. 43).
The study authors also calculated their own PCA values \19\ for
this assessment. EPA uses the maximum PCA calculated for any HUC8 (8-
digit hydrologic unit code) watershed in exposure estimates. HUC8s are
cataloging units for a watershed developed by the USGS and are used as
surrogates for drinking water watersheds. The process by which PCAs
were developed and how they are used by the Agency has been vetted with
the FIFRA SAP (Refs. 30 and 31). The Agency has developed PCAs for four
major crops--corn, soybeans, wheat, and cotton--and uses a default PCA
based on all agricultural land for characterizing other crops. The
Agency has also calculated regional default PCAs for use in
characterizing regional differences in drinking water exposure. EPA
limited further development of PCAs for additional crops in response to
the FIFRA SAP peer review, which concluded that the data were not
available at the appropriate scale to do so. The Petitioners'
assessment estimated PCAs for specific watersheds in Indiana, but did
not provide sufficient detail in their descriptions of how they
calculated those PCAs to enable EPA to assess their validity.
---------------------------------------------------------------------------
\19\ The PCA is the fraction of the drinking water watershed
that is used to grow a particular crop.
---------------------------------------------------------------------------
Regarding the statement that the concentrations estimated for the
study locations in Indiana are significantly less than EPA estimates,
EPA has determined that the Petitioners included an adjustment factor
to account for the percent of a crop that is treated with carbofuran.
As previously discussed, EPA does not believe that it is appropriate to
base its aggregate risk estimates on PCT within watersheds. This is
because data and/or methods are not available that would allow EPA to
develop PCT at the watershed scale with the necessary level of
confidence to allow EPA to make a safety finding. The PCT factors that
the Petitioners applied would generate significantly lower
concentrations than those estimated by EPA.
WARP Assessment
EPA has reviewed the WARP assessment previously and has provided
comments on the submission (Refs. 45 and 86). The WARP model has not
been fully evaluated for quantitative use in exposure estimation by the
Agency, although it has been preliminarily reviewed by the SAP (Ref.
32). EPA used WARP to select monitoring sites for the herbicide
atrazine, based on predicted vulnerability of watersheds to atrazine
runoff within the corn/sorghum growing regions. EPA presented its
approach to the FIFRA SAP in December 2007. The SAP report concluded
that ``WARP appears to be a logical approach to identify the areas of
high vulnerability to atrazine exposure,'' endorsing EPA's use of this
tool only for atrazine, and for the limited purpose of designing a
monitoring program. The SAP noted that the most important explanatory
variable with WARP was use intensity, which underscores the
[[Page 59662]]
importance of having the most accurate data for this parameter.
WARP is a regression model developed by the USGS to estimate
concentrations of the pesticide atrazine in rivers and streams. As a
regression model, it is based on monitoring data from 112 USGS NAWQA
monitoring locations. WARP does not directly estimate daily
concentrations, but predicts the percent of the time in a randomly
selected year that concentrations of the pesticide are less than a
specified value, with a specified level of confidence. USGS attempted
to develop an approach to estimate annual time series for other
pesticides, and concluded that ``further data collection and model
development may be necessary to determine whether the model should be
used for areas for which fewer historical data are available * * *
Because of the relative simplicity of the time-series model and because
of the inherent noise and unpredictability of pesticide concentrations,
many limitations of the model need to be considered before the model
can be used to assess long-term pesticide exposure risks'' (Ref. 92).
The Petitioners had previously relied on their WARP assessment to
support the conclusion that the ``maximum 1-in-10-day estimated
concentrations of carbofuran at the 90th percentile level in Illinois,
Indiana, Iowa, and Nebraska * * * will be less than or equal to 0.3687
ppb.'' This is erroneous. WARP does not provide direct estimates of
return frequency, i.e., 1-in-10 days, but rather percentiles of the
expected distribution of measurements. This may be similar but not
identical to the return frequency expressed as a percentile, depending
on the number of measurements used to support the regression. EPA
lacked the information necessary to determine whether the contractor
calibrated the model correctly. However, taking the conclusion at face
value, the value the Petitioners predicted using WARP, 0.3687 ppb,
appears to represent the maximum of the estimated values of the annual
90th percentile among all the sites evaluated. Such a site would be
expected to have higher concentrations than 0.3687 ppb about 37 days a
year (10% of the year). Generally, the 90% prediction intervals tend to
be about plus or minus an order of magnitude. Thus, roughly 5% of such
sites could have about 37 days a year greater than about 3.7 ppb, or
over 3-fold higher than the 1.1.ppb concentrations the Petitioners now
claim will be the maximum concentrations in surface water.
The Agency also disagrees that the differences between the
Petitioners' and EPA estimates are only due to Petitioners' use of
county-level use estimates. Most importantly, the Petitioners relied on
estimates of 1-in-10-day concentrations, rather than the 1-in-10-year
peak concentrations estimates used routinely by EPA. 1-in-10-day
concentrations are not the measurement endpoint EPA uses for human
health risk assessment and are not appropriate for estimating drinking
water exposure. The Agency uses 1-in-10-year peak concentrations for
screening level assessments, and the full time series (typically 30
years) of daily concentration values for refined assessments. EPA's
reliance on the 1-in-10-year peak concentration has been reviewed and
approved by the FIFRA SAP (Ref. 30).
A concentration that occurs 1-in-10 days occurs 350 times as often
as a 1-in-10-year event. Using this value instead of the one EPA used
would result in significantly lower estimates of pesticide water
concentration and human exposure. For example, EPA's estimate of the 1-
in-10-year peak concentration from the simulation of corn in Kansas
with a 300 ft buffer was 31.8 ppb. By contrast, EPA's estimate of the
1-in-10-day concentration from the same simulation was 4.5. Use of the
1-in-10 day concentration to assess dietary risk would be inconsistent
with the SAP's advice and EPA's typical practice, as well as with EPA's
statutory requirement to protect human health.
EPA disagrees with the Petitioners' claim that ``the extreme nature
of a 1-in-10-year event would result in dilution effects that cancel
out any increased loading.'' The Index Reservoir scenario has been
validated against monitoring collected at the site it was designed to
represent, Shipman City Lake in Illinois (Ref. 43). This assessment
showed that the 1-in-10-year event EPA modeled was similar in magnitude
to the peak value of the pesticide concentrations shown in 5 years of
monitoring data collected at that site. The 1-in-10-year peak
concentration calculated for that pesticide (not carbofuran), using the
Index Reservoir was 33 ppb, while the peak value from 5 years of
monitoring was 34 ppb.
EPA cannot determine the validity of the use intensities assumed
for the Petitioners' assessment. The source of county level use data
appears to have been sales data at the distributor level, similar to
the data provided in the Petitioners' November 7, 2008 submission.
However, as previously explained, the method chosen to estimate county
level use estimates from the sales data was not provided. The county
level estimates used in the assessment for 2002 to 2004 for Illinois
were provided in a table. These estimates for each county were averaged
over the 3 years for input to the model. A summary description of how
watershed-scale use estimated from county level use data was provided,
but because the sales data for the individual crops and the method that
was used to generate county level estimates were not available, the
validity of this assessment cannot be evaluated.
Nationwide CWS Assessment
EPA has previously reviewed the Petitioners' ``Nationwide CWS
Assessment'' and provided a response to the submission as part of the
final rule and Response to comments (Ref. 45). As a preliminary matter,
this assessment only included use intensity for reservoir-based
systems, and excluded use intensity for all stream- or river-based
systems from their assessment. Therefore, this assessment provides no
evidence to demonstrate that carbofuran can be safely used in stream or
river-based community water systems.
Similar to the Indiana CWS study discussed above, this study relied
on county-level usage estimates to estimate use intensity. The National
CWS Assessment concluded that a use intensity below 2.1 lbs a.i/mi\2\
would assure that surface water concentrations will be below the level
of concern.
To evaluate the study, it is therefore important to understand how
the use intensities were derived. The Petitioners' methods have been
poorly described, but EPA has been able to piece together a general
sense of the methods from the various reports provided to EPA. To
summarize, the Petitioners relied on sales data to generate the use
intensity estimates, but the method used to generate the county-level
use estimates from the sales data is not described. The actual county
level use estimates used in the use intensity calculations were not
provided. There is a limited description indicating only that the
county level use estimates were apportioned to different crops, but the
method used to do this was not provided. The Petitioners appear to have
used an objective method to group the county-level use estimates into 5
classes, but the method is only briefly described. Thus, because EPA
cannot determine how use intensity was estimated, the Agency cannot
determine if the conclusions made in the National CWS Assessment are
justified by the underlying data.
[[Page 59663]]
In the absence of this information, EPA is unable to substantiate
the study conclusion that 75% of the permissible use areas have a
carbofuran use intensity below 2.1 lbs a.i/mi\2\--even assuming that
reliance on only 75% of the use areas would be protective, and nothing
has been submitted to substantiate that conclusion. Use intensity maps
that were provided with the Petitioners' comments appear to indicate
that carbofuran use varies year by year, and it is not clear for which
year or years, the Petitioners are relying to support their claim that
use intensity will be below 2.1 lbs a.i/mi\2\. No further support for
this claim was provided with the Petitioners' objections, even though
EPA presented its conclusions in the final rule.
As noted, the National CWS Assessment assumed that a use intensity
below 2.1 lbs a.i/mi\2\ would assure that surface water concentrations
will be below the level of concern. EPA agrees that using lower rates
of carbofuran will result in lower exposure. But EPA does not agree
that it has been demonstrated that a use intensity below 2.1 lbs a.i./
mi\2\ will assure that surface water concentrations will be below the
applicable level of concern. The National CWS Assessment does not
justify such a finding, nor has any other assessment that has been
submitted to date. The Agency modeled use rates for carbofuran on corn
based on the label proposed in September 2008, which are the rates at
which farmers are legally allowed to apply carbofuran, and the results
clearly demonstrate that estimated exposures will substantially exceed
safe levels. The results of EPA's assessments are described in more
detail in Unit V.E. of this order, the final rule and in Reference 111.
EPA is equally unable to confirm the study's claim that the no-
application buffers on the September 2008 labels will adequately
mitigate the risks ``in areas with historical use intensities greater
than 2.1 lbs a.i./sq. mi.'' On the September 2008 labels, FMC included
buffers of 300 feet on water bodies in Kansas, and 66 feet around water
bodies in other places, but EPA cannot evaluate how these buffers
relate to areas where carbofuran use intensities exceeded a specific
value, for all of the reasons stated above. EPA did, however, model the
effects from the buffers proposed on the September 2008 labels and
found that these buffers reduce exposure by 5.1% (33.5 to 31.8 ppb) for
corn in Kansas with a 300-foot spray drift buffer and 4.7% (29.9 to
28.5 ppb) for corn in Texas with a 66-foot spray drift buffer. However,
even with the buffers, EPA's analyses clearly demonstrate that
estimated exposures will substantially exceed safe levels. These
results are described in more detail in Unit V.E. of this order, the
final rule, and Reference 84, Appendix I. For all of these reasons, the
objection is denied.
c. Objection/hearing request subissue: Challenges to EPA use of
NAWQA monitoring data. The Petitioners object to EPA's discussion in
the final rule of the extremely high concentrations detected in Zollner
Creek in Oregon. They argue that reliance on these concentrations to
confirm the results of EPA's modeling is not supportable because
Zollner Creek is a small isolated creek, not a drinking water source,
and that because of its size, is not representative of potential
drinking water anywhere else. They also argue that the majority of the
concentrations in the NAWQA data, including those detected at Zollner
Creek, are extremely low--below the 1.1 ppb they claim is supported by
their modeling. They also contend that the higher observed
concentrations in the NAWQA monitoring data are the result of use
patterns that are no longer permitted, and that allowed a much higher
use rate than is currently permitted.
i. Background. In the proposed rule, EPA described the available
monitoring data that characterized carbofuran concentrations in surface
water. EPA described that the highest concentrations of carbofuran are
reported from a sampling station on Zollner Creek, which EPA
acknowledged ``is not directly used as a drinking water source'' (73 FR
44883). USGS monitoring at Zollner Creek from 1993 to 2006 detected
carbofuran annually in 40-100% of the samples. EPA stated that although
the majority of the concentrations detected were in the sub-part per
billion range, concentrations have exceeded 1 ppb in 8 of the 14 years
of sampling (Id.). The maximum measured concentration was 32.2 ppb,
observed in the spring of 2002. EPA compared its modeling results to
the concentrations seen in all of the USGS monitoring, Safe Drinking
Water Act (SDWA) monitoring, and to the results of the available field
scale studies. EPA concluded that the concentrations estimated in its
modeling were consistent with the results of all of the available
monitoring and studies (73 FR 44883-44884).
In their comments on the proposed rule, the Petitioners alleged
that comparisons between EPA's modeling concentrations and Zollner
Creek detections were inappropriate because they were based on ``older
data [that] are not reflective of future carbofuran use areas and/or
intensities'' (Ref. 18 at 55). In support, they claimed that
``carbofuran was once used at several nurseries and strawberry farms in
the Zollner Creek watershed at estimated application rates of up to 15
lbs. a.i./acre (5 times higher than the maximum rate on the current
label, and 15 times higher than the most common use rates)'' (Id at
56).
In the final rule, EPA explained that it had not relied solely on
Zollner Creek concentrations to validate its modeling. EPA again
described the results of all available modeling, which included the
detections at Zollner Creek, but also included results from all other
NAWQA sites, SDWA post-treatment monitoring, and the results of field
studies. Based on all of these data, EPA concluded that the results of
the revised modeling conducted for the final rule was consistent with
the available monitoring data.
ii. Denial of hearing request. This subissue does not meet the
standard for a hearing. The objections regarding Zollner Creek are not
material. EPA did not rely in on the concentrations detected at Zollner
Creek to provide significant support its assessment.
In the final rule, EPA was clear that it considered the levels seen
at Zollner Creek to be a rare circumstance:
While available monitoring from other portions of the country
suggests that the circumstances giving rise to high concentrations
of carbofuran may be rare, overall, the national monitoring data
indicate that EPA cannot dismiss the possibility of detectable
carbofuran concentrations in some surface waters under specific use
and environmental conditions.
(74 FR 23081). The final rule was clear that EPA placed greater
reliance on the concentrations detected in Safe Drinking Water Act
(SDWA) post-treatment monitoring, showing concentrations ranging
between 4 and 7 ppb (74 FR 23079-23080). EPA also discussed the results
of the UK tile drain studies as supplemental confirmation of its
modeling (74 FR 23082).
Petitioners' contentions regarding the NAWQA monitoring also fail
to present a genuinely-disputed issue of material fact. In both the
proposed and final rules, EPA acknowledged the large percentage of non-
detections and low concentration levels in the majority of the NAWQA
monitoring data, and repeatedly explained the reasons that these data
cannot serve as lower or upper bounds (73 FR 44882-44883; 74 FR 23081).
Petitioners do not dispute those conclusions, or submit evidence to
rebut them. When an objector does not challenge EPA conclusions in the
final rule, but merely reiterates
[[Page 59664]]
comments made on the proposed rule, without submitting some evidence
that calls EPA final rule conclusions into question, the objector has
not raised a live controversy as to an issue material to the final
rule. (See 73 FR 42700-42701 (denying hearing request where NRDC failed
to object to the basis EPA asserted in its petition denial for
rejecting their original challenge). Finally, no evidence has been
submitted to support the contention that all of the higher
concentrations exclusively result from uses or higher use rates that
are no longer permitted. Hearings will not be granted on mere
allegations (40 CFR 178.32(b)(2)).
iii. Denial of objection. Data compiled in 2002 by EPA's Office of
Water show that carbofuran was detected in treated drinking water at a
few locations. Based on samples collected from 12,531 ground water and
1,394 surface water source drinking water supplies in 16 states,
carbofuran was found at no public drinking water supply systems at
concentrations exceeding 40 ppb (the MCL). Carbofuran was found at one
public ground water system at a concentration of greater than 7 ppb and
in two ground water systems and one surface water public water system
at concentrations greater than 4 ppb (measurements below this limit
were not reported). Sampling is costly and is conducted typically four
times a year or less at any single drinking water facility. The overall
likelihood of collecting samples that capture peak exposure events is,
therefore, low. For chemicals with acute risks of concern, such as
carbofuran, higher concentrations and resulting risk is primarily
associated with these peak events, which are not likely to be captured
in monitoring unless the sampling rate is very high.
Unlike drinking water derived from private ground water wells,
drinking water from public water supplies (surface water or ground
water source) will generally be treated before it is distributed to
consumers. An evaluation of laboratory and field monitoring data
indicate that carbofuran may be effectively removed (60-100%) from
drinking water by lime softening and activated carbon; other treatment
processes are less effective in removing carbofuran (Ref. 81). The
detections between 4 and 7 ppb, reported above, represent
concentrations in samples collected post-treatment. As such, these
levels are of particular concern to the Agency. An infant who consumes
a single 8-ounce serving of water with a concentration of 4 ppb, as
detected in the monitoring, would receive approximately 130% of the
aPAD from water consumption alone.
To further characterize carbofuran concentrations in surface water
(e.g., streams or rivers) that may drain into drinking water
reservoirs, EPA analyzed the extensive source of national water
monitoring data for pesticides, the USGS NAWQA program. The NAWQA
program focuses on ambient water rather than on drinking water sources,
is not specifically targeted to the high use area of any specific
pesticide, and is sampled at a frequency (generally weekly or bi-weekly
during the use season) insufficient to provide reliable estimates of
peak pesticide concentrations in surface water. For example,
significant fractions of the data may not be relevant to assessing
exposure from carbofuran use, as there may be no use in the basin above
the monitoring site. Unless ancillary usage data are available to
determine the amount and timing of the pesticide applied, it is
difficult to determine whether non-detections of carbofuran were due to
a low tendency to move to water or from a lack of use in the basin. The
program, rather, provides a good understanding on a national level of
the occurrence of pesticides in flowing water bodies that can be useful
for screening assessments of potential drinking water sources.
The national monitoring data indicate that EPA cannot dismiss the
possibility of detectable carbofuran concentrations in some surface
waters under specific use and environmental conditions. Even given the
limited utility of the available monitoring data, there have been
relatively recent measured concentrations of carbofuran in surface
water systems at levels above 4 ppb and levels of approximately 1 to 10
ppb measured in streams representative of those in watersheds that
support drinking water systems (Ref. 81). Based on this analysis, and
since monitoring programs have not been sampling at a frequency
sufficient to detect daily-peak concentrations that are needed to
assess carbofuran's acute risk, the available monitoring data, in and
of themselves, are not sufficient to establish that the risks posed by
carbofuran in surface drinking water are below thresholds of concern.
Nor can the non-detections in the monitoring data be reasonably used to
establish a lower bound of potential carbofuran risk through this route
of exposure. Nevertheless, these results are consistent with the
results of EPA's surface water modeling (Refs. 12, 47, 67). For all of
these reasons, the Petitioners objection is denied.
d. Objection/hearing request subissue: New label restrictions and
revised terms of registration. As discussed in Units VI.C and D, FMC
submitted a request to amend its existing registration to incorporate a
requirement intended to ensure that no more than 2% of any watershed
will be treated with carbofuran. Petitioners allege that these new use
restrictions will ensure that drinking water concentrations will not
exceed 1.1 ppb. In support, the objection presents a June 30, 2009
letter describing the restrictions, along with proposed revisions to
the carbofuran labels.
i. Background. On June 30, FMC requested that EPA amend its
registration to incorporate a requirement that, within five days of
applying the product, all applicators report to FMC the following
information: the location that the product will be used; crop, use
rate, application method, acreage, and quantity applied. Based on this
information, FMC would track the percentage in each watershed.
``Whenever it appears that carbofuran has been applied to 1.75% of any
watershed,'' the registrant would report that information immediately
to EPA, ``cease further sales in any county that overlaps with such a
watershed for that use season, and shall attempt to recall all unused
carbofuran within such counties by offering to repurchase such unused
product'' (Exhibit 3). In addition, FMC requested that its registration
be amended to require that ``based on watershed boundaries, FMC * * *
prior to each uses season, allocate to its distributors in a manner
which will attempt to ensure that no distributor receives more for
carbofuran for sale than can be accommodated by the 2% watershed area
cap in any watershed supplied by that distributor.''
ii. Denial of hearing request. EPA denies this hearing request on
two grounds. First, discussed in VI.C, Petitioners' objections and
hearing requests are denied as irrelevant, and therefore immaterial, to
EPA's determination in the May 15, 2009 final rule that the carbofuran
tolerances were unsafe and could not be sustained under FFDCA section
408. Petitioners are actually not objecting to the conclusions in EPA's
final rule; rather, they are suggesting that EPA might reach a
different result in a different factual scenario. Objections, however,
must be directed ``with particularity [at] the provisions of the
regulation or order deemed objectionable'' (21 U.S.C. 346a(g)(2)).
Further, as discussed in Unit VI.D, this objection is untimely, because
it was not raised in comments. Neither this specific proposal, nor any
other proposal regarding a potential tracking system, was presented to
EPA by the close of the September 29, 2008 comment period. EPA
therefore
[[Page 59665]]
considers this issue waived, and will not consider this as an
appropriate basis for justifying a hearing on its final rule.
However, there is a further equally material defect in this hearing
request. The Petitioners have submitted no evidence to support their
allegation that these proposed requirements would be effective in
ensuring that carbofuran would be applied to no more than 2% of any
watershed. The only submission was the description provided in the June
30 letter (Exhibit 3), and repeated above. However, this vague
description leaves several critical questions unanswered. For example,
the critical component of this proposal is a post-use reporting scheme,
with a five-day delay between use and reporting. Even assuming that one
accepts that reporting an address would allow for complete
identification of the location within an individual watershed--a point
on which no evidence has been submitted--no evidence, or even an
explanation, has been provided to demonstrate how this after-the-fact
reporting requirement will prevent application to greater percentages
of the watershed. For smaller watersheds, as discussed in the final
rule, application to only one or two farms may be sufficient to
substantially exceed 2% of the watershed. In such cases, since
applicators are only required to report within five days after
application, it is likely that FMC would not be informed until after
the 2% cap had been exceeded. Further, there will inevitably be some
delay between FMC's attempt to repurchase the product and the reports
suggesting (or confirming) that the cap either has been or will shortly
be exceeded. Given the inevitable delay, it is not unlikely that
further application would occur before FMC could even attempt to
repurchase the product. No details whatsoever have been provided
regarding the timing or mechanism by which this would occur. Further,
this program operates in the absence of any enforceable use
restriction, and no description of the means by which this would be
enforced is provided. Although the company would ``attempt to recall
the product'' or make it less available by ``attempting'' to direct
sales to particular distributorships, in the absence of some mechanism
to prevent sales or use, such as a permitting process, there is no real
assurance that these voluntary measures would be effective (Exhibit 3).
This is further complicated by the extremely low percentages
contemplated by this proposal.
Additionally, this scheme rests on a variety of assumptions that no
evidence has been submitted to substantiate. For example, the proposal
to restrict sales to distributors in particular watersheds rests on an
assumption that farmers always purchase products from a distributor
within their watershed. It also assumes that growers and distributors
will accept FMC's offer to repurchase unused stock of the products,
rather than seeking to stockpile the product for use in the next
growing season.
In the absence of any evidence to demonstrate the efficacy of these
proposed restrictions, any objection based on these proposed amendments
constitute no more than mere allegations or denials. Hearings will not
be granted on such a basis (40 CFR 178.32(b)(2)).
iii. Denial of objection. For the reasons discussed above, even if
it were appropriate to consider the proposed registration amendments,
EPA is unable to conclude that those amendments would ensure that
concentrations of carbofuran in drinking water derived from surface
water will not exceed 1.1 ppb. Accordingly, the objection is denied.
e. Objection/hearing request subissue: Consistency with NMC surface
water estimates. Petitioners object to EPA's surface water exposure
estimates on the ground that they are inconsistent with the estimates
EPA developed for purposes of the NMC CRA. Petitioners further claim
that their revised surface water assessment is consistent with the EPA
estimates in the NMC cumulative risk assessment. The evidence proffered
for this objection consists of the modeling in Exhibit 15.
i. Background. In comments on the proposed rule, the Petitioners
complained that as part of the NMC CRA, EPA relied on actual ``county-
or multi-county level pesticide use information, based on agricultural
chemical use surveys'' to develop its estimates of potential exposure,
rather than assuming 100% PCT.'' In the final rule, EPA provided a
lengthy and detailed explanation of the reasons that its approach to
assessing individual chemicals and its approach to assessing the
cumulative risks of multiple chemicals differed (74 FR 23067-23068 (May
15, 2009)).
ii. Denial of hearing request. To the extent Petitioners base this
objection on the concerns raised in their comments, EPA denies the
hearing request on this subissue because there is no disputed factual
matter for resolution at a hearing. There is no dispute that EPA
assumed 100% PCT for carbofuran in its surface water modeling, nor that
EPA developed lower estimates in the NMC CRA, that accounted for the
percent of the crop that was likely to be treated with each individual
NMC chemical in order to more accurately account for the likelihood of
pesticide co-occurrence at a single drinking water facility. Thus, the
only question is whether EPA's basis for adopting a different approach
between the assessment of a single chemical's aggregate exposure and
the assessment of the cumulative exposures from several chemicals is
reasonable. This question requires the application of a legal standard
to undisputed facts. Hearings are not appropriate on questions of law
or policy (40 CFR 178.32(b)(1)); (73 FR 42706-42707 (July 23, 2008)).
FDA has repeatedly confirmed that the application of a legal standard
to undisputed facts is a question of law for which a hearing is not
required. (See, e.g., 68 FR 46403, 46406 n.18, 46408, 46409 (August 5,
2003) (whether facts in the record show there is a reasonable certainty
of no harm is a question of law; whether a particular effect is a
``harm'' is a question of law)).
In addition, Petitioners have not challenged the substance of EPA's
response to their comments or submitted evidence that calls the
substance of EPA's conclusions into question (40 CFR 178.32(b)(3)).
Consequently, the Petitioners' objection on this issue is irrelevant,
and therefore immaterial, with regard to EPA's final tolerance
revocation regulation because Petitioners ignored EPA's extensive
analysis of this issue in the final rule and essentially resubmitted
their comments on the proposal as if EPA's determination in the final
rule did not exist. The statute, however, requires that objections be
filed on the final rule, not on the proposal (21 U.S.C. 346a(g)(2)). By
ignoring the EPA's final rule on this subissue, Petitioners have failed
to lodge a relevant objection. Both EPA and FDA precedent make clear
that when the agency substantively responds to comments on the
proposal, the commenter may only keep that issue alive in its
objections by addressing the agency's substantive response. See 73 FR
42698-42699 (When an objector does not challenge EPA conclusions in the
section 408(d)(4)(iii) order but rather challenges some prior
conclusion that was superseded by the section 408(d)(4)(iii) order, the
objector has not raised a live controversy as to an issue material to
the section 408(d)(4)(iii) order; 53 FR 53176, 53191 (December 30,
1988) (where FDA responds to a comment in the final rule, repetition of
the comment in objections does not present a live controversy unless
the objector proffers some evidence calling FDA's conclusion into
question)).
[[Page 59666]]
To the extent this objection is simply an allegation that the
results of the modeling are consistent with the surface water estimates
in EPA's NMC risk assessment, the hearing request also suffers from a
fatal flaw. The modeling is based on the assumption the recently
proposed label restrictions are effective, and that the PCT will be 2%.
Because the objection and hearing request are inextricably intertwined
with the Petitioners' newly submitted proposed FIFRA registration
amendments, the objection and hearing request are denied as irrelevant,
as discussed in Unit VI.C. Further, as discussed, no evidence was
submitted to support the assumption that the newly submitted use
tracking proposal will be effective. The only evidence submitted in
this regard is the results of the modeling in Exhibit 15, which as
previously discussed is untimely, and therfore provides an
inappropriate basis for a hearing. This evidence, therefore, on
multiple grounds is insufficient to support a reasonable possibility
that the issue will be resolved in the Petitioners' favor. No hearing
is warranted under such circumstances (40 CFR 178.32(b)(2)).
iii. Denial of objection. While it is true that in the NMC
assessment EPA used PCT numbers to estimate the cumulative exposure
from the contamination of such pesticides in surface water, this was
done in order to more accurately account for the likelihood of
pesticide co-occurrence at a single drinking water facility. But this
does not mean that use of PCT is appropriate in conducting an
assessment of aggregate exposure from carbofuran residues in surface
water. This difference in approach between the assessment of a single
chemical's aggregate exposure, and the assessment of the cumulative
exposures from several chemicals, stems from the differences in the
purpose and scope of the two assessments. These differences inevitably
require the application of different methodologies.
In evaluating the acute risks associated with a single chemical's
contamination of drinking water, EPA must consider all of the
variations permitted under the label. Drinking water exposures are
driven by uniquely local factors; not only is the source of drinking
water local (i.e., a person drinks water from his or her local water
system, not from a combination of water systems from across the United
States), but the likelihood and degree of contamination of any
particular, local drinking water source, whether it is a reservoir or
well, varies widely based on local conditions (e.g, from local pest
pressures, weather). Given this local variability, EPA must evaluate
how all of the practices permitted under the label will affect drinking
water exposures, because all are legally allowed, and farmers may
choose any of them based on their particular individual local
conditions. This means that even if growers, on a national or regional
basis, do not frequently use a particular practice, EPA must still
evaluate whether aggregate exposures from that practice would be safe
because the practice is legally permissible and may be used due to
local conditions. Thus, for example, even if most growers tend to apply
the chemical only to a portion of the field, or typically only apply
one-half of the maximum application rate, EPA must determine whether
use by all or some growers on the entire field or at the maximum rate
in a local watershed would result in unsafe drinking water
concentrations.
By contrast, it is not feasible to conduct the identical analysis
for a cumulative assessment of related chemicals. Since the potential
combinations of variations in pesticide use practices for the group of
pesticides to be assessed are essentially infinite, even with computer
modeling it would be impossible to model or evaluate all of the
combinations allowed under the labels. EPA therefore needed to narrow
its evaluation of the possible combinations to those deemed ``likely''
to occur. In contrast to the single chemical assessment, a cumulative
assessment is intended to develop a snapshot in time of what is likely
occurring at the moment. Moreover, the purpose of a cumulative
assessment is to identify major sources of risk that could potentially
accrue due to the concurrent use of several pesticides that act through
a common mechanism of toxicity. Thus, EPA is primarily interested in
the subset of circumstances in which residues from such pesticides
occur concurrently (or co-occur).
In addition, one of the important attributes of a cumulative risk
assessment is that its scope and complexity can potentially lead to
inflated estimates of risk due to compounding conservatisms, which
would reduce the interpretability and ultimately the utility of the
assessments. Because many data sets need to be combined, reducing the
impact and likelihood of compounding conservative assumptions and over-
estimation bias becomes very important in constructing a reasonable
cumulative risk assessment.
When little or no information is available to inform potential
sources of exposure, such as a reasonable or maximum watershed scale
PCT, it is both scientifically and legally reasonable for a single
chemical assessment to incorporate conservative assumptions to reflect
reasonable worst-case exposure estimates. But in a cumulative risk
assessment, the incorporation of such conservative assumptions would
imply multiple simultaneous reasonable worst-case exposure estimates
for each individual chemical. This is so unlikely that the results
would no longer represent even a reasonable worst-case estimate of the
likely risks. Consequently, some of the conservative assumptions
appropriately used in the single chemical risk assessments are not
appropriate or reasonable for use in a cumulative risk assessment, and
vice versa.
As a result, EPA chose in the NMC to work with those data that most
closely reflect ``representative'' exposures, and developed
``representative'' estimates of PCT in regional watersheds. However, to
be clear, the PCT values used in the NMC assessment do not represent
estimates of 50% of watersheds, or even the ``average'' watershed;
rather, they represent values that are expected to be as likely to be
accurate as not, based on a random selection of watersheds. A
comparable example is the statistic that the average American family
has approximately 2 children; this may or may not be true for any
individual family, but there is an equally good chance that it will be
accurate for any randomly selected family, as that it will not be
accurate. For the cumulative assessment, EPA is able accept this level
of uncertainty in these estimates, precisely because it has confidence
that aggregate exposures from the individual chemicals will be safe,
based on the level of conservatism in the single chemical assessments.
But given the statute's mandate to ensure a ``reasonable certainty of
no harm,'' EPA could not rely on the approach used under the cumulative
assessment in the absence of the more conservative single-chemical
assessment that evaluates the full range of exposures permitted by the
registration.
Nevertheless, as discussed in the final rule, in response to FMC's
concerns EPA performed a sensitivity analysis of an exposure assessment
using a PCT in the watershed to determine the extent to which some
consideration of this factor could meaningfully affect the outcome of
the risk assessment. The results suggest that, even at levels below 10%
CT, exposures from drinking water derived from surface waters can
contribute significantly to the aggregate dietary risks, particularly
for infants and children. Accordingly, these assessments suggest that
use of a reasonably conservative PCT estimate,
[[Page 59667]]
even if one could be developed, would not meaningfully affect the
carbofuran risk assessment, as aggregate exposures would still exceed
100% of the aPAD.
f. Objection/hearing request subissue: Natural surface water pH
conditions. The Petitioners contend that the low PCT levels guaranteed
by the recent proposed use tracking system, along with natural surface
water pH conditions in the areas where use is permitted under the
revised label will ensure potential exposures are de minimis. In
support they reference the analysis in Exhibit 16, which they claim
demonstrates that the NAWQA USGS data show that average surface water
pH is above 7.5 and that ``in most regions, moving 2 standard
deviations away from average (which would capture 95% of all observed
values) results in pHs that are still greater than 7.5.''
i. Background. In the proposed rule, EPA explained that the
variation in pH across the landscape was a significant uncertainty in
EPA's analysis. The proposal stated, that ``while it is well
established that carbofuran will degrade at higher rates when the pH is
above 7, and lower rates when below pH 7, due to the high variation of
pH across the country for many of the scenarios, a neutral pH (pH 7)
default value was used to estimate water concentrations (73 FR 44883).
Petitioners raised no issue regarding surface water pH in their
comments.
ii. Denial of hearing request. EPA denies this hearing request
because the objection, as well as the proffered evidence is untimely.
EPA clearly described the potential impact that pH could have on its
estimates, and noted that this was a significant uncertainty in its
assessment. None of the analyses in Exhibit 16 were provided as
comments on the proposed rule. Nor were any of the issues inherent in
this objection raised as comments on the proposal. Since the proposed
rule was clear that the issue was relevant, and the NAWQA data were
available, Petitioners could have conducted these analyses and raised
the issue as part of their comments. Consequently EPA has determined
that the evidence submitted in support of this objection is not
appropriately considered as a basis for justifying a hearing on its
final rule. And in the absence of this evidence, the objection consists
of mere allegations and general denials, which do not warrant a hearing
(40 CFR 178.32(b)(2)). Further, to the extent the objection and the
evidence in Exhibit 16 rely on use tracking system and risk mitigation
proposals submitted as part of their objections, this hearing request
is denied as irrelevant, and therefore immaterial, as discussed in Unit
VI.C. Petitioners are actually not objecting to the conclusions in
EPA's final rule; rather, they are suggesting that EPA might reach a
different result in a different factual scenario. Objections, however,
must be directed ``with particularity [at] the provisions of the
regulation or order deemed objectionable'' (21 U.S.C. 346a(g)(2)). In
addition, for the reasons discussed in Unit VI.D, any hearing request
premised on the new mitigation measures is considered untimely, and not
appropriately considered at this stage of the administrative process as
a basis for granting a hearing under the FFDCA.
EPA is also denying the requested hearing on the grounds that the
evidence, even if established, is insufficient to justify the action
urged (40 CFR 178.32(b)(3)). The analyses presented in Exhibit 16, as
the Petitioners explicitly acknowledge, only capture 95% of the values;
five percent of exposures are not, per se, de minimis. Second, just as
with the groundwater pH analyses presented in Exhibit 14, no
information was provided to explain how the samples relate to the state
or other geographic area in which carbofuran would be used. This is
important because NAWQA samples were not evenly distributed across most
states, but tended to be concentrated in particular regions; in
statistical parlance, the samples were not collected randomly. In other
words, no evidence was provided that would allow the Agency to
determine the percentage of the carbofuran use area represented by the
95% of the samples the Petitioners' analysis addressed. Nor was any
information provided to document the significance of the remaining 5%
of the samples that were not captured by their analysis; for example,
although this may have only represented 5% of the samples, it is not
clear whether this 5% relates to only 5% of the areas where carbofuran
may be used, or whether it actually represents a far greater percentage
of the use area. Because this information, even if established, would
provide an insufficient basis on which EPA could reasonably conclude
that the drinking water exposures would be ``safe,'' this issue is not
determinative.
iii. Denial of objection. For the reasons presented above, the
Petitioners' objection is denied. Further, there are several
significant defects with the analysis in Exhibit 16. First, the
analysis was based on statewide averages, which ignores the fact that
pH is not evenly distributed, but randomly clustered. Second NAWQA
contained no data for Kansas (KS), Oklahoma (OK), and South Dakota
(SD); Petitioners simply assert that the ``given the similarity between
these states and the other High Plains states, it is reasonable to
extend the observations from Colorado (CO), Nebraska (NE), and North
Dakota (ND)'' (Exhibit 16 at 4). Although the `High Plains' states all
have extensive areas of grassland, they also have extensive geographic
soil and climatic differences--e.g. the Black Hills and Badlands (SD),
Sand Hills (NE), Flint Hills, Cheyenne Bottoms and Quivira wetlands
(KS), Red Hills and Cross Timbers region (OK). These differences are
not surprising since the distance from the Canadian border in ND to OK
is over 1000 miles. Consequently it is not reasonable to extend
observations from CO, NE, and ND to KS, OK, and SD.
g. Objection/hearing request subissue: Effect of existing drinking
water treatment systems. The Petitioners contend that a review of
drinking water treatment systems in areas under revised labels
indicates that the majority of the ``total population in affected
states obtain their drinking water from surface water sources subject
to lime softening or activated charcoal filters. They allege that ``60%
of the total population in affected states'' will have their water
treated by methods that will substantially reduce or entirely remove
carbofuran concentrations. For the remaining 40%, they claim that a
significant portion use ground water sources, which are already
protected by the Petitioners' other mitigation measures, and the
remainder are protected by the Petitioners' proposed use reporting
scheme. In support of this objection, Petitioners rely on the analysis
in Exhibit 17.
i. Background. In the proposed rule, EPA explained that one of the
more significant uncertainties in EPA's analysis was that EPA failed to
account for the potential effect of treatment in removing carbofuran
from finished drinking water before it is delivered to the consumer
supply system. EPA explained that an evaluation of laboratory and field
monitoring data indicate that carbofuran may be effectively removed
(60-100%) from drinking water by lime softening and activated carbon;
other treatment processes are less effective in removing carbofuran
(Ref. 81). Although the Agency was aware of the mitigating effects of
specific treatment processes, the processes employed at public water
supply utilities across the country vary significantly both from
location to location and throughout the year, and therefore EPA was
unable to quantitatively incorporate this factor into its drinking
water exposure
[[Page 59668]]
estimates. For example, lime softening would likely reduce carbofuran
concentrations. That process is used in 3 to 21% of drinking water
treatment systems in the United States (Ref. 14). Activated carbon has
been shown to also reduce carbofuran concentrations, but is used in 1
to 15% of drinking water treatment facilities (Id.). Petitioners noted
this discussion in their comments, and relied on it to support their
argument that their drinking water exposure assessments were
conservative, because they did not account for the effect of treatment
(Ref. 18 at 46-55). However they submitted no comments raising any of
the issues or evidence presented in this objection.
ii. Denial of hearing request. EPA denies this hearing request on
the grounds that both the objection and the proffered evidence are
untimely. EPA clearly described the potential impact that treatment
could have on its estimates. None of the analyses in Exhibit 17 were
provided as comments on the proposed rule. Nor were any of the issues
inherent in this objection raised as comments on the proposal. Since
the proposed rule clearly identified the issue, and the USGS data were
available, the Petitioners could have conducted these analyses, or at
least raised the issue, as part of their comments. Consequently, as
discussed in Unit VI.D, EPA has determined that the evidence submitted
in support of this objection is not appropriately considered as a basis
for justifying a hearing on its final rule. In the absence of this
evidence, the objection consists of mere allegations and general
denials, which do not warrant a hearing (40 CFR 178.32(b)(2)). Further,
to the extent the objection and the evidence in Exhibit 17 rely on the
new registration proposals submitted in June 2009 as part of their
objections, this evidence as well is deemed both immaterial and
untimely. As discussed in Units VI.C and D, the new risk mitigation
measures are not appropriately considered at this stage of the
administrative process, and no hearing is warranted on this basis.
EPA is also denying this hearing request on the grounds the
Petitioners' evidentiary proffer is insufficient to justify the factual
issue urged (40 CFR 178.32(b)(2)). The analysis in Exhibit 17 is based
on the percentage of the total population across all states combined,
not the percentage of the local populations served by an individual
surface water source--or even the percentage within each state. Even
assuming that the 60% figure could legitimately be translated to a
state-by-state basis, their own analysis shows that some percentage of
the population in individual states will remain unprotected. In
Colorado, only 24% of the population obtains their drinking water from
groundwater, and in Illinois, only 33% of the population obtains their
drinking water from groundwater. Sixteen percent of Colorado's
population is not de minimis. Consequently, even if the analysis were
accurate, it would not provide a sufficient basis on which to conclude
that exposures from drinking water would be ``safe.''
A further consideration in this regard is that drinking water
exposures are driven by uniquely local factors; not only is the source
of drinking water local (i.e., a person drinks water from his or her
local water system not from a combination of water systems from across
the United States), but the likelihood and degree of contamination of
any particular, local drinking water source, whether it is a reservoir
or well, varies widely based on local conditions (e.g., from local pest
pressures, weather). Examining a population across an entire state--let
alone across several states--is an entirely inappropriate basis on
which to conclude that drinking water exposures will be safe.
The evidence submitted therefore does not support their contention
that 60% of the population in ``affected states'' obtain their drinking
water from public systems that use the treatment processes effective at
mitigating carbofuran residues. For example, Exhibit 17 shows that a
major Chicago surface water drinking water system, which serves a
population of 9,000,000, has neither lime softening processes nor
filters. Petitioners have submitted no evidence that this population is
protected. The fact that a small population remains unprotected is not
outweighed by the fact that a larger population in another community or
state is protected. Their own evidence also shows that only 26 of 141
of community water systems use lime softening/filters (Exhibit 17 at 4-
9), which supports the conclusion in the final rule that approximately
20% facilities have appropriate treatment. See 57 FR 33244 (7/27/92)
(Studies cited by NRDC do not provide a basis for the hearing because
they ``support the [FDA] conclusion in question.''); 57 FR 6667 (2/27/
1992) (``A hearing must be based on reliable evidence, not on mere
allegations or on information that is inaccurate and contradicted by
the record.''); 49 FR 6672 (2/22/84) (no hearing if claim based on
demonstrably false premise).
iii. Denial of objection. For the reasons discussed above, this
objection is denied. A further consideration is that treatment does not
necessarily remove all residues. As previously noted, in both the
proposed and final rules EPA discussed the SDWA monitoring detections
between 4 and 7 ppb, which represent concentrations in samples
collected post-treatment. As such, these levels are of particular
concern to the Agency. An infant who consumes a single 8-ounce serving
of water with a concentration of 4 ppb, as detected in the monitoring,
would receive approximately 130% of the aPAD from water consumption
alone. An infant who consumes a single 8-ounce serving of water with
the higher detected concentration of 7 ppb, as detected in the
monitoring, would receive approximately 220% of the aPAD from water
consumption alone.
G. Objections to EPA's Dietary Risk Assessment
Petitioners raise two related objections to the way in which EPA
evaluated the aggregate dietary exposures to carbofuran residues. First
they raise several technical challenges to the way in which EPA
calculated the two recovery half-lives that were used in the risk
assessment supporting the final rule to account for the potential for
individuals to recover from the effect of ingesting carbofuran residues
between exposures. Second, they object to the fact that in the final
rule EPA included both aggregate exposure estimates that did not
account for the potential for individuals to recover from the effects
between exposures as well as estimates that did account for such
recovery. In support the Petitioners cite to Exhibits 9 and 10. Exhibit
9 is a memorandum prepared by Robert Sielken and Ciriaco Valdez-Flores.
Exhibit 10 is a published literature study by Elsa Reiner that presents
data on the rates of spontaneous reactivation of phosphorylated and
carbamylated cholinesterases.
1. Objection/hearing request subissue: Inclusion of exposure
estimates that do not incorporate recovery in final rule. The
Petitioners object to the fact that the final rule presented aggregated
exposure estimates that did not incorporate the anticipated recovery
from carbofuran's effects between exposures, in addition to those that
did account for recovery. They claim that recovery time should be
included in EPA's ``primary'' risk assessment.
i. Background. As discussed in Unit V, EPA's standard acute dietary
exposure assessment calculates total dietary exposure over a 24-hour
period; that is consumption over 24 hours is summed and no account is
taken of the
[[Page 59669]]
fact that eating and drinking occasions may spread out exposures over a
day. This total daily exposure generally provides reasonable estimates
of the risks from acute dietary exposures, given the nature of most
chemical endpoints. Due to the rapid recovery associated with some
chemical toxicity (e.g., AChE inhibition), 24-hour exposure periods may
or may not be appropriate. To the extent that a day's eating or
drinking occasions leading to high total daily exposure might be found
close together in time, or to occur from a single eating event, minimal
AChE recovery would occur between eating occasions (i.e., exposure
events). In that case, the ``24-hour sum'' approach, which sums eating
events over a 24-hour period, would provide reasonable estimates of
risk from food and drinking water. Conversely, to the extent that
eating occasions leading to high total daily exposures are widely
separated in time (within 1 day) such that substantial AChE recovery
occurs between eating occasions, then the estimated risks under any 24-
hour sum approach may be overstated. In that case, a more sophisticated
approach--one that accounts for intra-day eating and drinking patterns
and the recovery of AChE between exposure events--may be more
appropriate. This approach is referred to as the ``Eating Occasions
Analysis'' and it takes into account the fact that the toxicological
effect of a first dose may be reduced or tempered prior to a second (or
subsequent) dose.
In the proposed rule, EPA conducted an Eating Occasion analysis
based on two half-lives: 150 minutes and 300 minutes (73 FR 44887 (July
31, 2008)). These half-lives were not specific to carbofuran, but were
calculations derived for the NMC Cumulative Risk Assessment. EPA
concluded that incorporating these analyses into the risk assessment
had little impact on the risk estimates from exposures from food alone,
but that risk estimates from combined exposures from food and water
were reduced by approximately 2-3X (Id). However, because many of EPA's
risk concerns stemmed from a single exposure (e.g., one meal) and
because, even when recovery was accounted for, aggregate exposures far
exceeded safe levels, EPA concluded that ``risks to carbofuran is
indeed not substantively overestimated using * * * the 24-hour
approach'' (Id).
In their comments, Petitioners complained that EPA had failed to
incorporate recovery into their risk assessment. They further argued
that EPA should calculate the per capita 99.9th percentile based on all
person minutes rather than all person-days. In addition, they submitted
an aggregate dietary risk assessment they had conducted using a 150-
minute half-life input. They submitted no explanation for using only
the 150-minute half-life rather than also including estimates based on
the 300-minute half-life that EPA has used for the proposed rule.
In the final rule EPA explained that it had conducted a revised
Eating Occasion analysis to evaluate the impact of carbofuran's rapid
reversibility on its risk estimates (74 FR 23086 (May 15, 2009)). EPA
concluded that incorporating Eating Occasion Analysis and the 186-
minute or 426-minute recovery half-lives for carbofuran did not
significantly change the risk estimates for food exposures alone (74 FR
23086 (May 15, 2009)). EPA concluded that risk estimates based on
combined food and drinking water exposures are reduced considerably--by
a factor of two or more in some cases, but nonetheless still
substantially exceed EPA's level of concern for infants and children.
EPA also explained that the Agency remains concerned about the risks
from single eating or drinking events. Finally, EPA noted that the
Eating Occasion Analyses underestimate exposures to the extent that
they do not take into account carry-over effects from previous days,
and because drinking water concentrations are randomly picked from the
entire 30-year distribution (Id at 23087).
ii. Denial of hearing request. EPA is denying this hearing request
on two grounds. First, the objection fails to present a disputed issue
of material fact. The record is clear that EPA did incorporate recovery
into its analysis; indeed, one of Petitioners' objections relates to
the manner in which EPA incorporated recovery into its risk assessment
(Obj at 30-33). Rather, their only challenge is that the final rule
should have only presented risk estimates that accounted for recovery.
The sole issue is whether it was reasonable for EPA to have also
communicated aggregate risks that did not account for recovery, when
(1) EPA's estimates showed that accounting for recovery demonstrated
that EPA's standard 24-hour estimates were not substantially
overstated; (2) EPA's approach to accounting for recovery
underestimates some risks; and (3) EPA's risk assessments concluded
that infants received unsafe exposures from a single meal (eating
occasion). This is a policy issue, and hearings are not appropriate on
such (40 CFR 178.32(b)(1)).
Second, the fact that EPA relied on 24-hour aggregate exposures in
addition to analyses that accounted for recovery is not material. As
documented in the final rule, EPA would still have concluded that
revocation of all tolerances were warranted on the grounds that, even
accounting for recovery, aggregate exposures are not ``safe.'' Even
though accounting for recovery resulted in a 2-3X reduction in exposure
estimates, many of EPA's estimates for aggregate exposures ranged
between 2700% aPAD and 9400% aPAD for infants. Accounting for recovery
does not, therefore, demonstrate that aggregate exposures will be safe
for infants. Of greater significance in this regard is EPA's finding
that infants are at risk from a single exposure. Recovery is only
relevant, by definition, where the risk is derived from multiple
exposures over time.
iii. Denial of objection. The reason for not simply adopting the
assessment incorporating recovery time was that the Agency has concerns
that other aspects of its exposure model tends to understate exposure.
If the assessment using recovery time had suggested that carbofuran
risks may be acceptable, EPA would have had to further examine how
exposure was assessed. However, because both the assessment based on
24-hour exposure and the one incorporating recovery time showed
carbofuran exposures to be well over the safe level, EPA concluded that
its exposure assessment was reasonable. As explained in the final rule,
incorporating Eating Occasion Analysis and the 186-minute or 426-minute
recovery half-lives for carbofuran resulted in a reduction in the risk
estimates for which food and drinking water are jointly considered
(i.e., Food + Drinking Water) by a factor of two or more in some cases.
But even though the risk estimates from aggregate exposure are reduced,
they nonetheless still substantially exceed EPA's level of concern for
infants and children. Using drinking water derived from the surface
water from the Idaho potato surface water scenario, which estimated one
of the lowest exposure distributions, aggregate exposures at the 99.9th
percentile ranged from 328% of the aPAD under the scenario for which
infants rapidly metabolize carbofuran (e.g., 186-minute half-life), to
a high of 473% of the aPAD under the scenario for which infants
metabolize carbofuran more slowly (e.g., scenarios in which a 426-
minute half life is assumed). Either way, the tolerances are unsafe.
Moreover, even accounting for the estimated decreased risk from
accounting for carbofuran's rapid reversibility, for which recovery
between exposures is irrelevant. The Agency remains concerned about the
[[Page 59670]]
risks from single eating or drinking events, as illustrated in the
following example, based on an actual food consumption diary from the
CSFII survey. A 4-month old male non-nursing infant weighing 10 kg is
reported to have consumed a total of 1,070 milliters (ml) of indirect
water over eight different occasions during the day. The first eating
occasion occurred at 6:30 a.m., when this 4 month old consumed 8 fluid
ounces of formula prepared from powder. The FCID food recipes indicate
that this particular food item consists of approximately 87.7% water,
and therefore, 8 ounces of formula contains approximately 214 ml (or
grams) of indirect water; with the powder (various nutrients, dairy,
soy, oils, etc.) accounting for the remaining 12.3%. This infant also
reportedly consumed a full 8-ounce bottle of formula at 12 p.m., 4
p.m., and 8 p.m. that day. The food diary also indicates that the
infant consumed about 1 tablespoon of water (14.8 ml) added to prepare
rice cereal at 10 a.m., about 2 ounces of water (59.3 ml) added to pear
juice at 11 a.m., another \1/2\ tsp of water (2.5 ml) to prepare more
rice cereal at 8:30 p.m.; and finally, he consumed another 4 ounces of
formula (107 ml) at 9:30 p.m.
The infant's total daily water intake (1,070 ml, or approximately
107 ml/kg/day) is not overly conservative, and represents substantially
less than the 90th percentile value from CSFII on a ml water/kg
bodyweight (ml/kg/bw) basis. As noted, carbofuran has been detected in
finished water at concentrations of 4 ppb. For this 10 kg body weight
infant, an 8-ounce bottle of formula prepared from water containing
carbofuran at 4 ppb leads to drinking water exposures of 0.0856
micrograms of active ingredient/kilogram of bodyweight ([mu]g ai/kg
bw), or 114% of the aPAD from that bottle alone. Based on the total
daily water intake of 1,070 ml/day (no reversibility), total daily
exposures from water at 4 ppb concentration would amount to 0.4158
[mu]g ai/kg bw, or 555% of the aPAD; this is the amount that would be
used for this person-day in the Total Daily Approach.
Peak inhibition occurs following each occasion on which the infant
consumed 8 fluid ounces of formula (6 a.m., 12 p.m., 4 p.m. and 8
p.m.); however, the maximum persisting dose occurs following the 9:30
p.m. eating occasion, based on a 186-minute half-life parameter. This
produces a maximum persisting dose of 0.1457 [mu]g ai/kg bw, or about
30% of the total daily exposure of 0.4158 [mu]g ai/kg bw derived above,
or expressed as a fraction of the level of concern, the maximum
persisting dose amounts to about 194% of the aPAD (or 30% of 554%).
Note that with drinking water concentration at 4 ppb, an infant
consuming one 8 oz bottle of formula--prepared from powder and tap
water containing carbofuran at 4 ppb will obtain exposures of
approximately 114% of aPAD. Since many infants consume the equivalent
of this amount on a single eating occasion, accounting for
reversibility over multiple occasions is not essential to ascertain
that infants quite likely have obtained drinking water exposures to
carbofuran exceeding the level of concern based on drinking water
concentrations found in public drinking water supplies.
The approach discussed above is used to evaluate the extent to
which the Agency's 24-hour approach to dietary risk assessment
overestimates risk from carbofuran exposure. The results of both
approaches indicate that the risk from carbofuran is indeed not
substantively overestimated using the current exposure models and the
24-hour approach.
In this regard, it is important to note EPA's Eating Occasion
Analyses underestimate exposures to the extent that they do not take
into account carry-over effects from previous days, and because
drinking water concentrations are randomly picked from the entire 30-
year distribution. As discussed previously, DEEM-FCID is a single day
dietary exposure model, and the DEEM-based Eating Occasion Analysis
accounts for reversibility within each simulated person-day. All of the
empirical data regarding time and amounts consumed (and corresponding
exposures based on the corresponding residues) from the CSFII survey
are used, along with the half-life to assess an equivalent persisting
dose that produced the peak inhibition expected over the course of that
day. This is a reasonable assumption for food alone; since the time
between exposure events across 2 days is relatively high (compared to
the half-life)--most children (>9 months) tend to sleep through the
night--and the time between dinner and breakfast the following morning
is long enough it is reasonable to ``ignore'' persisting effects from
the previous day. A single day exposure model will underestimate the
persisting effects from drinking water exposures (formula) among
infants, and newborns in particular (<3 months), since newborns tend to
wake up every 2 to 4 hours to feed. Any carry over effects may be
important, especially if exposures from the previous day are relatively
high, since the time between the last feeding (formula) of the day and
the first feeding of the subsequent day is short. A single day model
also does not account for the effect of seasonal variations in drinking
water concentrations, which will make this effect more pronounced
during the high use season (i.e., the time of year when drinking water
concentrations are high). Based on these analyses, the Agency concludes
that the current exposure assessment methods used in the carbofuran
dietary assessment provide realistic and high confidence estimates of
risk to carbofuran exposure through food and water.
In summary, there are several factors that may cause EPA's
exposure/risk model to either understate or overstate exposure/risk. It
is unreasonable to present risks only incorporating factors that tend
to reduce exposure/risk estimates (e.g., recovery time), as Petitioners
suggest. EPA's approach of evaluating the impact that these factors may
have on the risk assessment is an appropriate method of taking all
relevant factors into account. Petitioners' objection to EPA's policy
decision to present acute risks in terms of 24-hours of exposure is
therefore denied because EPA's policy approach here is reasonable.
2. Objection/hearing request subissue: Technical challenges to
EPA's calculated half-lives. Petitioners contend that EPA's calculation
of carbofuran half-lives of 186 minutes and 426 minutes were flawed,
and that the data instead support the use of a 150-minute half-life.
Petitioners identify three specific challenges: (1) Because one of the
time course studies showed that the time-to-peak effect was one hour,
EPA's assumption that the time-to-peak effect in each study was 15
minutes is incorrect; (2) EPA included the control rats in its
modeling, which distorts the estimated recovery half-life because it
incorporates AChE from animals that were not dosed and did not need to
recover; (3) Biochemically, the recovery half-lives of all NMC
chemicals should be the same, which supports the use of a 150-minute
half-life. In support of these claims, Petitioners offered a summary of
written testimony from Drs. Sielken and Valdez-Flores (Exhibit 9) and a
published study (Exhibit 10).
i. Background. In the proposed rule, EPA relied on half-lives of
150 minutes and 300 minutes (73 FR 44887). These values were calculated
for the NMC cumulative risk assessment and so were intended to
encompass the half-lives for all of the NMC pesticides.
In the final rule, EPA calculated half-lives specific to carbofuran
to ensure that its analyses accurately reflected carbofuran's risk.
Using the two FMC
[[Page 59671]]
time course studies in rat pups EPA calculated half-lives for recovery
of 186 and 426 minutes (Id). The two values were derived from two
different studies using rat pups of the same age (Refs. 24, 25); the
two values provide an indication that half-lives to recovery can vary
among juvenile rats. By extension, children are expected to vary in
their ability to recover from AChE inhibition where longer recoveries
would be associated with a potentially higher ``persisting dose.''
ii. Denial of hearing request. The issue of the appropriate half-
lives for carbofuran is not material. Petitioners have proffered no
evidence to show that reliance on a 150-minute half-life rather than a
186-minute half-life would make a significant difference to their
estimates. By contrast, in the risk assessment supporting the final
rule, EPA's estimates show that the use of a 150-minute or 186-minute
half-life makes little or no difference. For example, EPA's estimated
exposures from food alone for children 1-2 were 43% of the aPAD,
assuming a 186-minute half-life, and 41% of the aPAD, assuming a 150-
minute half-life. Similarly, for infants, the estimates ranged from 31%
aPAD, assuming a 186-minute half-life, and 30% of the aPAD, assuming a
150-minute half-life. For all other age groups, the estimated exposures
were identical, whether one assumed a 150-minute or 186-minute half-
life.
In any event, Petitioners' objection would have ultimately no
effect on the Agency's conclusion that the carbofuran tolerances are
not ``safe.'' Given EPA's assessments showing that a single exposure
can result in excessive risks to infants--a conclusion that Petitioners
have not challenged--the extent of recovery between subsequent
exposures is irrelevant. This conclusion alone provides an adequate
basis to revoke the carbofuran tolerances. Accordingly, because the
action would be the same even if the factual issue were resolved in the
manner sought, this request does not meet the standard for granting a
hearing (40 CFR 178.32(b)(3)).
There is yet a further consideration affecting the materiality of
this objection. EPA's recalculation of half-lives in the final rule
would ordinarily mean that Petitioners could appropriately challenge
EPA's methodology for deriving the revised half-lives for the first
time in their objections. This is because the Petitioners would have
had no prior opportunity to challenge the manner in which these
estimates were developed, as EPA had not previously relied on
carbofuran-specific estimates. However in this case, the Petitioners
never commented on the 300-minute estimate EPA used in the proposal,
nor raised any issue to challenge the reliance on a longer half-life to
account for the variation in children's sensitivity. For the reasons
discussed in Unit VI.D, they have therefore waived any objection to use
of a 300-minute half-life. Accordingly, the question of whether the
Petitioners' half-life of 150-minutes or EPA's estimated half-life of
186-minutes is immaterial, since the lower amount of recovery
associated with the longer 300-minute half-life would be expected to
have a far greater impact than the use of a 186-minute half-life.
EPA is also denying the hearing request because the evidentiary
proffer in support of this objection is inadequate. Petitioners have
not provided the underlying analyses conducted in support of their
calculated half-lives. The remainder of Exhibit 9 consists of
contentions that EPA's analyses were mistaken. In the absence of the
analyses that support their claim that the data support a half-life of
150 minutes, Petitioners' evidentiary proffer consists of no more than
mere allegations and denials. Hearings will not be granted on this
basis (40 CFR 178.32(b)(2)) (See 73 FR 42706 (July 23, 2008) (``NRDC
does no more than state `[w]e are aware of no statistical test' which
would support EPA's use of the Gledhill data. As EPA's regulations make
clear, a mere `denial' of an EPA position is not sufficient to satisfy
the standard for granting a hearing'') (citations omitted); 53 FR
53176, 53199 (December 30, 1998) (``Rather than presenting evidence
[the objector] asserts that FDA did not adequately justify its
conclusions. Such an assertion will not justify a hearing.'').
The published paper in Exhibit 10 does not cure this defect. The
paper was submitted to support the claim that the Petitioners' 150-
minute half-life is consistent with the ``available literature on the
AChE recovery'' (Obj at 32). This evidence is immaterial. The Reiner
paper relates to the reactivation of the AChE enzyme; however the
relevant issue is not the reactivation of the cholinesterase enzyme,
but the level of chemical in that target tissue, which this study does
not address. Moreover, this study concludes that ``[I]t follows from
the data in Tables 1 and 2 that the rate of spontaneous reactivation
cannot be predicted, but must be separately determined for each
compound and each enzyme source (Exhibit 10 at 1). The paper did not
include data specifically on carbofuran, and it is therefore difficult
to see how this could be argued to support the Petitioners' half-life
of 150-minutes.
iii. Denial of objection subissue. All of Petitioners' claims are
incorrect.
Appropriate time to peak effect. The Petitioners claim that the
time to peak effect in the study with MRID 47143704 (Ref. 2) should
have been 1 hour instead of the 15 minutes EPA calculated. Petitioners
chose this value simply by choosing the data point with the highest
level of inhibition. But this approach is flawed in a number of
regards: First as a practical matter, using the same criteria on which
the Petitioners rely, the time to peak effect in MRID 46688913 (Ref. 3)
is 15 minutes. Petitioners have presented no basis for excluding those
results.
More significantly, the Petitioners' approach fails to account for
the variability of the estimated AChE activity at each time point. As a
point of background, the level of the highest inhibition is not
something that can be observed, in the way that motor activity is
observed. To determine inhibition, samples are taken and measured--the
samples may or may not capture the highest point of inhibition; the
technician has not external indicia that will determine the moment of
the ``peak.'' Determining peak inhibition is estimated based on the
available measurements. But because measurements are generally
variable--the animals differ and the sampling itself is not identical,
as people cannot perfectly replicate their actions time after time--in
order to accurately capture the peak levels, the variability needs to
be accounted for. When, as here, the individual values are quite
variable, then for a half-life as long as carbofuran's, the sampling
variability will make the study means bounce up and down around a trend
line representing the true recovery rate. Figure 2 illustrates the
sampling variability of the measured AChE activity and its relationship
to EPA's modeling estimates for PND11 pups. In brief, this plots
observed versus predicted for all the data. Each little point is an
individual animal, while the time-group mean is the larger version of
the same plotting symbol. The vertical lines are the 95 percent
confidence intervals for each mean, the vertical lines. The diagonal
line in each figure is the identity line--i.e., the line all the data
would fall on if there were no variability and the model were perfect.
Normally, one would expect some random scatter about the identity line.
In such a case, simply visually picking the time with the lowest mean,
which is what the Petitioners have done, will
[[Page 59672]]
not be a very reliable way to estimate the time to peak effect.
[GRAPHIC] [TIFF OMITTED] TR18NO09.001
Inclusion of data from control animals. It is standard scientific
practice to include concurrent control animals (i.e., animals that are
not dosed with the test substance) as part of any experimental design.
The purpose of controls is to determine the effects of the inevitable,
unexpected, and uncontrolled variations in experimental practice, such
as the biological variation between individual living animals. EPA's
model simply used control levels to establish a baseline against which
to evaluate the recovery of the treated animals. For example, as
discussed above, measurements of AChE activities may change, and that
concurrent controls are set up so that the same non-dose-related
factors that affect treated animals will also affect control animals.
Thus, EPA measured activity and computed inhibition based on measures
of activity in treated animals and concurrent control animals. Thus, if
the control animals showed that measured levels of AChE typically
varied by 5 percent, if the dosed animal showed inhibition levels of 20
percent, EPA would consider that only 15 percent of the inhibition
would be related to the chemical exposure. EPA did not estimate a half-
life of recovery for the control animals and incorporate that into the
estimated half-lives, which seems to be the Petitioners' allegation.
Biochemically, the recovery half-lives of all NMC chemicals should
be the same. Although the Petitioners' claim that the recovery rate of
AChE inhibited by carbamate compounds is dictated by the commonly-
shared NMC carbamyl group is theoretically plausible, in reality, it is
not supported by the data on the NMC compounds. EPA had originally
hoped, based on the same mechanistic argument Petitioners make, that
half-lives would be the same across all NMCs, thus greatly simplifying
the cumulative risk assessment. It turned out, though, in the NMC data
sets analyzed for the NMC cumulative risk assessment, that estimated
recovery half-lives changed (generally, they got longer) as dose
increased, which is counter to the results that would be predicted from
the Petitioners' simple mechanistic argument (Ref. 81). Ultimately,
this is due to the fact that the relevant question is not the abstract
reactivation of the cholinesterase enzyme, but the level of chemical in
the living animal's target tissue, which is a function both of the
pharmacokinetics of the NMC (i.e., the rate at which the chemical is
absorbed, distributed among tissues, and eliminated) in the animal and
the rate of hydrolysis of the leaving group off the AChE molecule.
These parameters vary at least somewhat for the different carbamates,
accounting for the differences in half-lives between the NMC
pesticides.
H. Objection to EPA's Decision Not To Rely on Carbofuran Human Study
Petitioners object to EPA's reliance on a default 10X interspecies
factor, which accounts for the uncertainties inherent in extrapolating
from animal data to the anticipated effects in humans. They argue, for
several reasons, that EPA should have instead used a 3X interspecies
factor. All of their arguments, however, depend on EPA consideration of
an oral carbofuran dosing study conducted in humans. EPA did not rely
on the cited human study because it found, taking into account the
advice of the HSRB, that the study was scientifically invalid. EPA's
Human Research rule prohibits EPA from considering scientifically
invalid human studies (40 CFR 26.1701). In their objections,
Petitioners argue that the HSRB's, and presumably EPA's, evaluation of
the scientific validity of the human study was flawed because (1) the
human study was not considered in light of the animal data on
carbofuran; (2) insufficient weight was given prior independent reports
on the value of the Arnold study which reached the opposite conclusion
from the HSRB; (3) the ``technical'' concerns raised by the HSRB are
addressed by ``the data within the study'' and that these ``technical''
deficiencies do not render the Arnold study unreliable.
1. Background. There are three intentional dosing human studies
conducted with carbofuran that were conducted by J.D. Arnold in 1976,
1977, and 1978. One study was an oral ingestion toxicity study and two
studies were intended to evaluate toxicity from dermal exposure (Refs.
7, 8, 9). The oral study conducted with carbofuran was carried out in
nine healthy male
[[Page 59673]]
volunteers using an ascending dose schedule and single doses of 0.05,
0.1 and 0.25 mg/kg (Ref. 7). The two dermal toxicity studies were found
to have significant ethical deficiencies and the EPA's Human Studies
Review Board recommended against their use. The Petitioners do not
challenge the decision to disregard these studies.
As previously noted, EPA did not rely upon any of the existing
intentional dosing human toxicity study deriving an acceptable level of
exposure for carbofuran. Instead, EPA relied on data conducted with
rats, and applied the default 10 x interspecies factor to account for
the potential uncertainty in extrapolating from animal data. EPA's
decision not to rely on the Arnold studies was made pursuant to its
Human Research rule. As explained in Unit III.B, that rule establishes
different ethical standards for the review of completed human studies
depending on whether they were initiated before or after the effective
date of the rule on April 7, 2006. For an intentional human exposure
study such as the Arnold studies, that was initiated prior to April 7,
2006, EPA is barred, subject to a very limited exception, from relying
on it if there is clear and convincing evidence that the conduct of the
research was fundamentally unethical or significantly deficient with
respect to the ethical standards prevailing at the time the research
was conducted (40 CFR 26.1704, 26.1706). Further, the rule limits the
human research that can be relied upon by EPA to ``scientifically valid
and relevant data'' (40 CFR 26.1701). Finally, because the Arnold study
was conducted with the purpose of identifying or measuring a toxic
effect, EPA is required by the rule to submit its determination
regarding these issues to an independent expert advisory body known as
the Human Studies Review Board (``HSRB'') for review. These procedures
were followed with regard to the Arnold study.
The HSRB reviewed the Arnold oral and dermal carbofuran human
studies at its May, 2006 meeting (Refs. 7, 8, 9). The Board found
numerous technical deficiencies regarding the conduct of the oral study
and that overall, the weaknesses of the studies far outweigh the
strengths. These deficiencies included: (1) There was no justification
or rationale for the selection of doses used in any of the three
studies. (2) The sample size was very small (typically two subjects per
dose or condition) with few or no controls (no more than two control
subjects in any study). Such a design prevented evaluation of
statistical significance for any parameter measured in the studies. (3)
The values obtained for RBC and plasma cholinesterase levels were
highly variable. Factors that contributed to this variability included
the small sample size, the inclusion of only a single baseline sample
collected immediately prior to dosing used to compare all post-dosing
samples, the small number of control subjects, and an uncommon method
for analytical determination of cholinesterase activities. The
contribution of potential laboratory error cannot be ruled out. (4)
Plasma cholinesterase levels were highly variable in all studies so as
to preclude any useful interpretation. In general, plasma
cholinesterase levels were not consistent with changes in RBC
cholinesterase activities. (5) One subject who presented with abnormal
vestibular mechanisms in the pre-dose evaluation was used in the oral
study and showed serious symptoms after treatment. (6) Subjects were
allowed to smoke during the study period.
In response to a specific request from the Agency, the Board
provided additional analysis concerning the potential for the data in
human subjects for carbofuran to be applied to: (1) The calculation of
a benchmark dose (BMD10) and identification of the
BMD10L (lower confidence limit); (2) the identification of a
NOAEL or LOAEL for effects or (3) the comparison to other species for
possible adjustments to uncertainty factor for the cumulative
assessment. The HSRB provided the following additional perspective
relative to the Agency's question:
The utility of the human studies with carbofuran was limited by
the very small sample size used in all of the studies. The Agency
proposed to use the RBC cholinesterase data for determination of the
BMDL10. However, under conditions where the group size
was only two, it would be imperative to have highly accurate, valid,
reliable and consistent measures of RBC cholinesterase activity in
both control and carbofuran-treated subjects. This rigor was simply
not achieved in the human studies. Rather, RBC cholinesterase
activities were compared to a single baseline value, were highly
variable across subjects, including controls, and did not show any
consistency with plasma cholinesterase levels. As such, although EPA
scientists calculated a BMDL10 from the time course of
changes in RBC cholinesterase values in the nine subjects evaluated
in the oral study, the HSRB concluded that the accuracy and
reliability of this calculation was limited by the technical
shortcomings noted for the study. Therefore, the HSRB reiterated its
recommendation that the BMDL10 calculated by the Agency
from the human data should not be used.
In a similar manner, the small sample size, compounded by the
lack of consistent changes in cholinesterase activities in all
studies, the inappropriate methods used for dermal application of
the compound in the dermal studies and the inclusion of at least one
subject who presented with abnormal vestibular function in a pre-
dose assessment limited the general utility of the data.
Collectively, the weaknesses in the conduct and outcomes of the
carbofuran human studies cast doubt on the utility of the data for
identifying a NOAEL or LOAEL or for comparing across species in
consideration of the interspecies uncertainty factor for the
cumulative risk assessment. Thus the majority of HSRB members agreed
the human oral data should not be used to identify a NOAEL or LOAEL,
and there was unanimous agreement that the human dermal data should
also not be used for these evaluations.
The HSRB concluded that while these studies were informative, due
to the numerous technical issues regarding the conduct of the oral
study, overall, the weaknesses of the studies far outweigh the
strengths. Describing the studies as ``poor science,'' the HSRB
recommended against the use of the oral study conducted with carbofuran
in human subjects for the single chemical assessment or in informing
the interspecies uncertainty factor for the cumulative assessment.
In their comments opposing EPA's proposal to revoke carbofuran
tolerances, Petitioners essentially raised the same arguments they
present in their objections.
In responding to Petitioners' comments, EPA explained that it
agreed with the HSRB's conclusions that the studies were scientifically
flawed, and that, therefore, under the Human Research rule, EPA was
barred from considering them (Ref. 85 at 9).
2. Denial of hearing request. The critical issue here is EPA's
determination under the Human Research rule that the Arnold study was
scientifically invalid. All of Petitioners' arguments concerning the
choice of the interspecies safety factor rely on EPA's consideration of
the Arnold study. As noted above, Petitioners make three arguments as
to why EPA erred in its determination. For the reasons discussed below,
none of those arguments satisfy the regulatory standard for granting a
hearing. Further, as explained in Unit VI.H.3., Petitioners' objections
to EPA's determination have no merit. Thus, there is no need to
consider Petitioners' more general arguments about EPA's decision to
use a 10X interspecies factor in assessing carbofuran's risk.
Petitioners' first argument as to why EPA erred in its
determination that the Arnold study was scientifically invalid is that
EPA failed to consider the animal data on carbofuran in assessing the
scientific quality of the Arnold study. This claim is not material and
thus not
[[Page 59674]]
appropriate for a hearing (40 CFR 178.32(b)(3)). Under the Human
Research Rule, the relevant question is whether the Arnold study is
scientifically valid, not whether consideration of the Arnold study in
conjunction with the animal data could justify a lower interspecies
factor. EPA, and the HSRB, found the Arnold study to be flawed at its
core--due primarily to its small sample size and the high variability
in measurement of AChE inhibition--and no amount of data from other
studies in animals can cure these defects in the Arnold study. Thus,
Petitioners' claim here is irrelevant and immaterial to EPA's decision.
Ultimately, Petitioners' objection is a challenge to the policy
established in the Human Research rule that EPA will not routinely
consider all human data. They contend that ``[s]ince [human] data exist
for carbofuran, they should have been used to select the interspecies
uncertainty factor.'' However, this policy question is not open for
debate under the terms of the Human Research rule. And more
importantly, such a question does not provide a basis for a hearing (40
CFR 178.32(b)(1)).
Second, Petitioners argue that insufficient weight was given the
prior independent reports on the Arnold study. However, the weight EPA
should give under the Human Research rule to pre-rule independent
reviews as opposed to the conclusions of the HSRB--the body established
by the rule for the purpose of aiding EPA's implementation of it--is a
legal/policy question and not a factual one. Hearings will not be
granted on legal/policy issues (40 CFR 178.32(b)(1)).
Finally, Petitioners' claims that EPA and the HSRB identified
merely ``technical'' deficiencies in the Arnold study and that these
deficiencies are ``address[ed]'' by ``data within the study itself''
and, therefore, do not render the study ``unreliable'' are no more than
mere allegations and thus provide an insufficient basis for the
granting of a hearing (40 CFR 178.32(b)(2)). Petitioners have proffered
no evidence regarding the ``technical'' nature of the deficiencies in
the Arnold study or how the deficiencies in sample size or variability
are addressed within the study. Moreover, the record is clear that the
deficiencies in the study are fundamental in nature and a hearing will
not be granted on bald objections that are contradicted by the record
(73 FR 42696 (July 23, 2008) (hearing denied when objection was
contradicted by record and no evidence proffered in support)).
3. Denial of objection. Petitioners have offered no response to
EPA's explanation for accepting the HSRB's reasoning as to the
weaknesses of the studies that rendered them scientifically invalid.
Specifically, Petitioners do not address the HSRB's conclusion, adopted
by EPA, that ``the weaknesses in the conduct and outcomes of the
carbofuran human studies cast doubt on the utility of the data for * *
* comparing across species in consideration of the interspecies
uncertainty factor.'' Nor do Petitioners offer any reason as to why the
HSRB's conclusion is not ``justifiable'' in light of the individual
peer review reports from Drs. Brimijoin, Chambers, and Pope. Actually,
there are several very good reasons for EPA to place primary weight on
the HSRB's report compared to the three individual reports from Drs.
Brimijoin, Chambers, and Pope prepared in 1997. First, the prior
reports were not produced under the rubric of the Human Research rule,
which has a different scope of inquiry than a traditional peer review.
Second, Drs. Brimijoin, Chambers, and Pope made their recommendation
regarding use of the Arnold study for a RfD in the context of a very
different overall database for carbofuran. A significant number of new
toxicity studies have been submitted since 1997. Third, Drs. Brimijoin,
Chambers, and Pope all noted the severe deficiencies in the Arnold
study but proposed that they be dealt with through the use of
additional safety factors. Given these considerations it was reasonable
for EPA to place primary reliance on the HSRB's report.
The bulk of Petitioners' argument concerning EPA's determination on
the scientific validity of the Arnold study is devoted to suggesting
that the HSRB's review of the Arnold study was somehow ``inadequate''
because two members of the HSRB (Drs. Brimijoin and Chambers) were
recused from the review due to their prior participation in a prior
independent peer review. Petitioners also assert that the HSRB was
hampered because EPA ``never informed the HSRB that it could call upon
these experts for questioning or information regarding their prior peer
review of the human studies, nor was it informed of--or provided with--
those prior reviews.''
These claims are wholly without merit. As laid out in a letter
responding to FMC's complaint regarding the recusal of Drs. Brimijoin
and Chambers from the HSRB review of the carbofuran human studies, the
recusal was entirely appropriate, and consistent with EPA's policies
and regulations. The facts outlined in that letter also demonstrate
that the HSRB's review was in no way restricted or hampered by the
limited recusal of the two Board members.
First, the HSRB was fully apprised of the earlier peer review
reports. EPA relied on the reports because EPA's position before the
HSRB was that the Arnold study should be found to meet the standard of
the Human Research rule and would be useful in establishing points of
departure for the carbofuran's single chemical assessment and in
informing the interspecies uncertainty factor for the NMC CRA. It was
clearly in EPA's interest that the HSRB be made aware of the earlier
reports. In fact, the background materials provided to the Board
included the peer review reports by Drs. Brimijoin, Chambers, and Pope,
and the Agency's Weight-of-the-Evidence presentation to the HSRB which
noted the contributions of these reviewers. Further, both the peer
review reports and EPA's Weight-of-Evidence presentations were included
in the public docket for the HSRB review. To the extent that the HSRB
was still somehow unaware of the prior reports, FMC clearly referenced
them in both its written and oral comments to the Board.
Second, EPA's determination on the recusal of Drs. Brimijoin and
Chambers was clearly consistent with Agency policy and well with EPA's
discretion. The EPA's Peer Review Handbook (3rd Edition) (Ref. 80)
provides guidance about peer review processes of the Agency. Of
particular relevance is the Handbook's guidance regarding independent
peer reviewers. While the Handbook notes that there is no prohibition
against using the same peer reviewer more than once on the same
product, it nevertheless advises that ``it is preferable to use
different people each time to provide a broader perspective (Ref. 80 at
13). Further the Handbook advises that the review of experts who ``have
participated substantially in the development of a product * * * may
not qualify as unbiased, independent peer review * * *'' (Id.).
Therefore, EPA concluded that, under the circumstances, a question
could be raised regarding the impartiality of Drs. Brimijoin and
Chambers from the particular matter under review by the HSRB. Further
support on this point can be found in the regulations at 5 CFR
2635.502(a)(2), and in the preamble to the original regulation (56 FR
33778 (July 23, 1991)).
In light of these considerations, EPA addressed the appearance
issue regarding Drs. Brimijoin and Chambers by determining whether
authorization by the Agency designee should be invoked (see, 5 CFR
2635.502(d)). Three factors were particularly relevant to the
determination of Drs. Brimijoin and Chambers (see, 5 CFR
2635.502(d)(4), (5), and (6)): the sensitivity of the
[[Page 59675]]
matter, the difficulty of reassigning the matter to another employee,
and adjustments that may be made in the employee's duties that would
reduce or eliminate the likelihood that a reasonable person would
question the employee's impartiality. After considering these factors,
the Agency decided the prudent course was be to recuse Drs. Brimijoin
and Chambers from the HSRB carbofuran discussion but to authorize
limited, as needed, participation.
As documented in Dr. William Farland's May 1, 2006 memorandum
entitled, ``Ethics Determination for Participation at the May 2-3, 2006
EPA Human Studies Review Board Meeting'' (Ref. 39), EPA authorized the
HSRB to ask Drs. Brimijoin and Chambers clarifying questions regarding
their 1997 review, in the event that the HSRB deemed it necessary as
part of their deliberations. At no point during the meeting did any of
the HSRB's members indicate in any way that they wanted to consult with
their recused colleagues. Nor did any of the members state that they
wanted clarification on any point associated with the study.
For all of the above reasons, Petitioners' objection on this point
is denied.
I. Objections to Revocation of Import Tolerances
Petitioners object to EPA's revocation of the tolerances for
imported foods along with the tolerances associated with domestic uses.
Petitioners allege that the revocation of the import tolerances is not
supported by the available data because EPA's own risk assessments
conclude that, when considered separately from the domestic uses, the
residues from imported foods covered by these tolerances are ``safe.''
Petitioners further argue that EPA ``has not asserted any claim or
rationale in the Final Order justifying its conclusions that the import
tolerances are unsafe'' and therefore the revocation is unjustified.
1. Background. In the proposed rule, EPA explained that its finding
that aggregate exposure from all of the existing uses of carbofuran is
not safe does not necessarily mean that no individual tolerance or
group of tolerances could meet the FFDCA 408(b)(2) safety standard and
be maintained (73 FR 44865 (July 31, 2008)). Rather, to the extent
parties wanted to retain a particular subset of existing tolerances,
the onus was on commenters to identify those uses and to submit
information to demonstrate that the tolerance(s) meet the statutory
standard. Indeed, EPA specifically identified the import tolerances as
a subset that might meet the safety standard (Id.).
No one submitted any comments alleging the need to retain
individual tolerances for purposes of imports, or indicated an
intention to seek to maintain those tolerances. The only subset of
tolerances that commenters suggested was safe was the subset identified
by the Petitioners, which included the import tolerances along with
four domestic food uses.
In the final rule, EPA analyzed the aggregate exposures from the
subset of tolerances the Petitioners sought to retain, and concluded
that the aggregate residues from food covered by those tolerances and
from residues in drinking water are unsafe (74 FR 23084-23088).
2. Denial of hearing request. A hearing is denied on this subissue
because there is no disputed factual matter for resolution at a
hearing. As the objection notes, EPA and Petitioners' risk assessment
both concluded that the residues from imported food alone fell within
the risk cup (Obj. at 52-54). The only issue this objection raises is
whether EPA should have independently determined to retain a subset of
the tolerances that Petitioners sought to maintain. This is a legal
issue, and hearings are not appropriate on such issues (40 CFR
178.32(b)(1)). (See 73 FR 42696-42697 (July 23, 2008) (denying NRDC's
request for a hearing on objection that children's safety factor could
not be reduced in absence of endocrine screening data). FDA also has
repeatedly confirmed that the application of a legal standard to
undisputed facts is a question of law for which a hearing is not
required. (See, e.g., 68 FR 46403, 46406 n.18, 46408, 46409 (August 5,
2003) (whether facts in the record show there is a reasonable certainty
of no harm is a question of law; whether a particular effect is a
``harm'' is a question of law)).
In addition, Petitioners failed to raise this issue as part of
their comments on the proposed rule, and never requested retention of
only the import tolerances. Accordingly, as discussed in Unit VI.D, EPA
considers this issue to have been untimely raised, and therefore
waived. (See, 73 FR 42,696 (July 23, 2008) (denying NRDC's hearing
request on claims not presented in their original petition); 72 FR
39318, 39324 (July 18, 2007) (ruling that parties may not raise new
issues in filing objections to EPA's denial of original petition)).
3. Denial of Objection. Petitioners incorrectly allege that EPA
provided no rationale for the revocations of the import tolerances. In
the final rule, EPA clearly found that the aggregate exposures to
carbofuran residues from all remaining uses, when combined with
residues found in drinking water, were unsafe (74 FR 23084-23088 (May
15, 2009).
EPA can only maintain tolerances that it can determine will be
``safe'' within the meaning of section 408(b)(2)(A)(ii). In making this
determination, EPA must consider aggregate exposures from ``dietary
exposure under the tolerance and all other tolerances in effect for the
pesticide chemical residue, and exposure from other non-occupational
sources'' (21 U.S.C. 346a(b)(2)(D)(vi)). At the time of the final rule,
EPA evaluated the safety to the public from all dietary exposures to
residues of carbofuran, which included not only the import tolerances,
but also from residues on foods associated with domestic registrations
and from residues in drinking water contaminated by the domestic uses.
Indeed, until domestic use ceases--or at least until EPA has a
reasonable basis to believe that it will cease--the Agency has no
discretion to ignore the exposures from those uses. And revocation of
the tolerances themselves does not necessarily resolve the issue, given
the circumstances here. Until the registrations are cancelled, residues
from contaminated drinking water, which is the primary contributor to
the risks, must be included in EPA's risk assessment (Id).
The consequence of this requirement is that, when one tolerance is
unsafe, all tolerances are equally unsafe until aggregate exposures
have been reduced to acceptable levels. Accordingly, in circumstances
where aggregate exposures exceed the risk cup, there are potentially
multiple variations of the potential subset of tolerances that might
meet the safety standard. FFDCA section 408 does not compel EPA to
determine the appropriate subset that would meet the safety standard.
EPA is compelled ``to revoke or modify a tolerance if [EPA] determines
it is not safe,'' but the statute grants EPA the discretion to
determine how to proceed where more than one tolerance is unsafe. EPA's
general policy in such situations is not to independently select the
subset that meets the standard, but to rely on the pesticide registrant
and the public to determine which of the various subsets of tolerances
are of sufficient importance to warrant retention. There are a number
of reasons EPA adopted this policy; it would be an unreasonable burden
for the Agency to evaluate every possible combination of tolerances
that might fit within the risk cup. In addition, if there were multiple
different combinations that might within the risk cup, it is not clear
that any party would
[[Page 59676]]
agree that EPA had selected the appropriate combination of tolerances.
This is particularly relevant, since EPA relies on individual entities
to maintain the tolerance, by continuing to submit necessary data to
demonstrate the continuing safety of the covered residues.
J. Summary of Reasons for Denial of Petitioners' Objections and Hearing
Requests
1. General Denial. All of Petitioners' objections and hearing
requests are denied because they are irrelevant, and thus immaterial,
to EPA's final regulation revoking carbofuran tolerances. The lack of
relevance stems from Petitioners' decision to object not to the safety
decision EPA made in its final revocation regulation but to instead
argue that EPA should reach a different decision based on FMC's
proposed changes to the carbofuran registration that were submitted to
EPA 44 days after the regulation published in the Federal Register.
These proposed registration changes are central to and inextricably
intertwined with the contention that underlies all of Petitioners'
objections--that the carbofuran tolerances are safe, because in order
to retain the contested tolerances, Petitioners must succeed on all of
their objections. There exist statutory and regulatory procedures under
FIFRA for FMC to pursue an amended carbofuran registration. As part of
seeking an amended registration, FMC may petition to reestablish the
revoked carbofuran tolerances. However, it is not proper to object to a
final FFDCA tolerance revocation regulation based on the assertion that
subsequently-filed, and as of yet unapproved FIFRA registration
amendments, may change the risk picture under the FFDCA.
FMC has had ample opportunity prior to issuance of the final
tolerance revocation regulation to amend its FIFRA registration,
whether during the comment period on the proposed rule, the extended
reregistration process, or the public process initiated as part of the
NOIC for carbofuran. And FMC has requested a number of modifications to
its registrations during that time period. Yet, FMC has waited until
EPA issued a final revocation regulation finding that carbofuran
tolerances are unsafe, particularly as to infants and children, before
filing its latest series of proposed FIFRA registration amendments. For
this FFDCA proceeding, that is too late. The FFDCA commands that EPA
``shall modify or revoke a tolerance if the Administrator determines it
is not safe'' (21 U.S.C. 346a(b)(2)(A)(i)). The statute also places EPA
under a special injunction to protect infants and children from the
risks of pesticides (21 U.S.C. 346a(b)(2)(C)). EPA has made a final
determination that carbofuran tolerances are unsafe and further
determined that that lack of safety falls hardest on infants and
children. Petitioners had the statutory right under FFDCA to challenge
the accuracy of EPA's safety finding on carbofuran tolerances. FMC also
has the statutory right under FIFRA to request amendment of its
registration. What Petitioners may not do is prolong the FFDCA
tolerance revocation process by challenging EPA's safety determination
based on proposed FIFRA registration changes that were not before EPA
at the time of its final revocation decision.
2. Alternate Grounds for Denial. Despite the fact that Petitioners'
objections and hearing requests are facially defective for reliance on
newly-proposed FIFRA registration amendments, EPA has carefully
examined each of Petitioners' objections and hearing requests and found
that, in every instance, there are alternate grounds for denial. Those
grounds are summarized below.
There are multiple problems with Petitioners' hearing requests.
Many of these problems stem from the Petitioners' decision to withhold
analyses and information from the notice-and-comment rulemaking portion
of this proceeding. Thus, despite EPA's clear warning that issues not
raised in comments on the proposed rule, and information not submitted
in that same timeframe, would be considered waived, Petitioners
included several new issues, and numerous documents and analyses for
the first time with their objections although they were clearly
available earlier. Petitioners also have, for the most part, ignored
how EPA responded to the comments they did submit in the notice-and-
comment rulemaking, and instead have often merely recycled their
earlier comments as objections without addressing the reasons why EPA
found them lacking in the first instance. This strategy, unfortunately
for Petitioners, is fatal to many of their hearing requests and
objections. EPA will not grant hearings on issues that have been
waived, on issues where supporting documents were untimely submitted,
or on claims that have become stale in that EPA addressed them in the
final rule and Petitioners have not responded by clarifying where
disputed issues still remain.
It is not as if Petitioners lacked warning that EPA would take such
an approach. Not only did EPA clearly state in the proposed rule that
comments and information must be submitted in the comment period to be
preserved but in 2007 EPA denied a hearing to a party who treated the
notice-and-comment rulemaking process in a similarly cavalier fashion.
In that instance, the party in question, like Petitioners, filed
objections that largely mirrored its earlier submissions to the Agency
without taking into account how EPA's final action had altered the
nature of issues in dispute (See, e.g., 73 FR 42693 (``NRDC's
objections largely restate the claims in its petition. Significantly,
NRDC does not acknowledge or respond to the DDVP dietary and
residential risk assessments made in response to the NRDC
petition.'')). Such objections and hearing requests were denied for a
lack of materiality (73 FR 42698-42699 (``When an objector does not
challenge EPA conclusions in the section 408(d)(4)(iii) order but
rather challenges some prior conclusion that was superseded by the
section 408(d)(4)(iii) order, the objector has not raised a live
controversy as to an issue material to the section 408(d)(4)(iii)
order.'').
a. Children's Safety Factor Objection. In support of their
objection on the children's safety factor, Petitioners put forward
several arguments; EPA summarizes below the various reasons for
rejecting Petitioners' hearing requests and objections on each
argument. Given the voluminous number of arguments asserted by
petitioners in support of this objection, it is easy to lose track of
the fact that all of the arguments relate to a single decision by EPA--
the decision to reduce the presumptive 10X children's safety factor to
4X, rather than to 1X or 2X as the Petitioners desire.
(i) Subissue: Are brain AChE measures in juveniles adequately
protective of CNS effects in juveniles? EPA based its determination to
reduce the children's safety factor to 4X on the ratio of sensitivity
shown between carbofuran's effects on RBC AChE and brain AChE in
juvenile rats. It is EPA's general policy to rely on RBC AChE as a
surrogate for effects on the PNS but Petitioners failed to provide
adequate RBC AChE data in juveniles to fully characterize the dose
level of concern for PNS effects in infants and children. Petitioners
claim EPA was wrong from the start. They claim that once EPA determined
it had adequate data on brain AChE, the RBC data was irrelevant because
brain AChE is an adequately-protective surrogate for PNS effects.
Petitioners' hearing requests and objections on this issue are
denied for identical reasons: the available evidence
[[Page 59677]]
identified by petitioners is ``insufficient to justify the factual
determination urged'' (40 CFR 178.32(b)(2)). The critical issue with
regard to EPA's children's safety factor decision is whether EPA has
reliable data to ensure that residues of carbofuran in food will not
cause adverse effects on infants and children's PNS. Petitioners claim
that carbofuran data on brain AChE in juveniles is such reliable data.
However, the evidence they proffer to support such an assertion is
facially insufficient. Primarily, Petitioners cite data involving
comparisons of brain AChE and PNS effects in adult animals. But
evidence from adult animals is beside the point; the question is
whether brain AChE in juveniles is protective of the PNS in juveniles.
For at least 25 years, EPA has required toxicity tests be performed
with pre- and post-natal animals as well as adult animals because young
animals can be more sensitive and affected in a different manner than
adults. Further, the only studies Petitioners cite that compared brain
AChE in juveniles with PNS effects in juveniles, were conducted using
other pesticides. For good reason, EPA requires that pesticides be
individually tested in toxicity studies. Moreover, the majority of the
data cited by Petitioners in other chemicals actually fails to
demonstrate that the brain is more sensitive than the PNS, and the
remainder of the evidence is, at best, merely equivocal on this point.
To reiterate, if EPA chooses to select a children's safety factor
different than 10X, it bears the statutory burden of showing that
reliable data support its determination that the selected factor is
safe for infants and children. Thus, Petitioners, in seeking to
establish that EPA erred by not selecting an even lower children's
safety factor for carbofuran (in fact, no such factor at all),
similarly bear the burden of showing that there are reliable data for
the proposition that juvenile brain AChE data for carbofuran are
protective of PNS effects in children. Petitioners' equivocal and
largely irrelevant proffer cannot meet that standard, particularly
where EPA is lacking data it has traditionally-required on
cholinesterase-inhibiting pesticides to protect against PNS effects,
and the data EPA does have on measures of PNS effects indicate that
effects on the juvenile PNS occur at lower doses than effects on brain
AChE.
(ii) Subissue: Are RBC AChE measures adequately reliable evidence
of CNS effects? As a corollary to their claim that brain AChE measures
are adequately protective of PNS effects, Petitioners also argue that
RBC is not an appropriate surrogate for CNS effects in most
circumstances. A hearing is not warranted on this subissue because
Petitioners' evidentiary proffers either concern matters of undisputed
fact (e.g., RBC AChE inhibition is not an adverse effect, RBC AChE can
be variable at low doses) or inadequate and irrelevant data on other
pesticides. Further, Petitioners' claim basically reduces to an
argument over which is the ``preferred'' surrogate for PNS effects in
the absence of data directly measuring such effects. Thus, this
subissue is an argument about science policy and EPA's regulations are
clear that hearings will not be held on policy matters. Even more
problematic to Petitioners' hearing request on this subissue is its
lack of materiality. Having failed in the previous subissue to proffer
sufficient evidence to show carbofuran brain AChE data in juveniles is
protective of carbofuran's effect on the PNS in juveniles, Petitioners'
attempt to attack EPA's basis for addressing carbofuran's effects on
the PNS in juveniles can only undercut Petitioners' ability to
demonstrate the safety of the carbofuran tolerances. With the demise of
Petitioners' brain AChE argument, EPA's analysis of the RBC AChE data
is the only remaining basis for reducing the children's safety factor.
If Petitioners are successful in showing that RBC AChE data are not a
reliable measure of PNS effects in juveniles, EPA would have no
reliable data on such impacts and would be required to retain the full
children's safety factor. As such, Petitioners' claim is immaterial;
even if the claim were upheld, it would not justify the ultimate relief
sought by Petitioners.
As to Petitioners' objection to EPA's science policy decision to
use RBC cholinesterase as a surrogate for PNS effects, EPA explains in
detail in Unit VI.E, the biological basis for its policy decision, the
multitude of data supporting its approach, and the frequent
consultations with the SAP concerning the wisdom of using such an
approach. The equivocal data submitted by Petitioners does not raise a
serious question regarding EPA's policy. In any event, as noted with
regard to the hearing request, this subissue lacks materiality in that
success on this subissue by Petitioners would retard rather than
advance their challenge to EPA's action.
(iii) Subissue: Is ``lip-smacking'' a CNS or PNS effect?
Petitioners object that EPA's evidence of ``lip smacking'' in a
carbofuran adult developmental rat study does not support concern for
potential PNS effects because lip smacking is more properly correlated
to CNS, rather than PNS inhibition. A hearing is denied on this issue
because Petitioners did not raise this issue in its comments on the
proposed tolerance revocation. A hearing on this issue is also
inappropriate because the issue is immaterial. EPA's decision that a 4X
children's safety factor is appropriate did not rest exclusively--or
even significantly--on the effects observed in this developmental
study. Rather, EPA retained the children's safety factor based on the
lack of data in the PNS and/or a surrogate at the low end of the
response curve, and the fact that the available pup RBC data at higher
doses affirmatively indicate that the PNS appears to be significantly
more sensitive than the CNS.
Petitioners' objection on this subissue is denied because both
parties agree that muscle fasiculations, which are the movements EPA
described at the SAP meeting and in the proposed and final rules, are
PNS-mediated effects. Further, it is unclear that the effects described
in the studies Petitioners submitted are actually the same effects seen
in the carbofuran study; other factors in the studies suggest that the
movements being studied are not purely cholinergic, which calls into
question whether the effects are the same. For the same reason, this
calls into question the contention that the effects are exclusively
CNS-related. Finally, the cited studies fail to support Petitioners'
remaining contentions. Since it is unclear that the studies actually
describe the same effects, and Petitioners have failed to demonstrate
that the effects are exclusively CNS-related, the evidence does not,
therefore, rebut EPA's conclusions regarding the movements described in
the carbofuran study.
(iv) Subissue: Did EPA err by relying on studies not conducted
pursuant to EPA's GLP regulations? Petitioners claim that EPA's
reliance on the ORD data is problematic because the data were not
conducted in accordance with EPA's GLP regulations at 40 CFR part 160.
Petitioners have not cited any evidence suggesting there is a
substantive problem with the ORD data or made any arguments to such
effect. Thus, this subissue presents only a legal question and legal
questions are not appropriate grounds for a hearing. EPA denies
Petitioners' objection on this point because EPA regulations make clear
its GLP regulations only apply to studies in support of a pesticide
registration or tolerance (40 CFR 160.1(a), 160.3). In any event, non-
compliance with the GLP regulations does not automatically disqualify a
study from EPA consideration but rather goes to reliability (40 CFR
160.17(a)).
[[Page 59678]]
(As noted, Petitioners have made no claim that the ORD data is not
reliable.).
(v) Subissue: Was EPA's selection of a 4X children's safety factor
consistent with EPA's approach to other carbamate pesticides?
Petitioners object that EPA was inconsistent in retaining a 4X
children's safety factor for carbofuran given that EPA removed the
children's safety factor for other carbamates. A hearing is not
appropriate on this subissue because it presents a purely legal
question. There is no dispute regarding the facts of EPA's decision in
each case, the only question is whether EPA acted appropriately on
carbofuran given its decision on the children's safety factor for other
carbamate pesticides, such as carbaryl. The objection is denied because
EPA's decisions in each case were consistent; EPA applied a different
children's safety factor to carbofuran than to the other carbamate
pesticides based on the different facts in each case. For example, the
data showed that carbaryl differed significantly from carbofuran in
terms of each chemical's relative sensitivity in juveniles with regard
to brain and RBC AChE inhibition. For carbofuran, EPA concluded that
RBC AChE inhibition in juveniles was more sensitive than brain AChE
inhibition in juveniles by a factor of 4X. For carbaryl, the AChE
inhibition in brain and RBC of juveniles was essentially equal.
(vi) Subissue: Did EPA err in not using within-animal brain to RBC
AChE inhibition comparisons to derive the children's safety factor? EPA
derived an alternate to the default 10X children's safety factor based
on the ratio of RBC and brain AChE inhibition. In their comments on the
proposed rule, Petitioners criticized this approach, arguing that EPA
should have compared the RBC and brain AChE inhibition levels at the
same time in the same rat when these rats are exposed to carbofuran.
Petitioners claimed to have done such an analysis and that the analysis
showed that within rat inhibition levels in brain and RBC AChE were
roughly equivalent. Although the results of the statistical analyses
were summarized in the comments, the underlying analysis was not
submitted. In the final tolerance revocation regulation, EPA
extensively reviewed the ``within animal'' approach and rejected it as
fundamentally flawed in several regards. Additionally, EPA noted that
EPA's review of the Petitioners' suggested approach showed that it
produced results, which are in fact consistent with EPA's conclusions.
In their objections, Petitioners do not respond to EPA's rejection of
the within animal approach in the final tolerance revocation rule
either by explaining their disagreement with EPA's critique or
proffering evidence to counter EPA's conclusion. Rather, Petitioners
simply resubmitted essentially the same comments they provided on the
proposed rule. Petitioners also again failed to submit the underlying
analysis supporting their within animal calculations.
A hearing on this subissue is not appropriate for two reasons.
First, Petitioners' repeated failure to submit the analysis supporting
their claim reduces this objection to a mere allegation. Under EPA's
regulations, hearings will not be granted on the basis of mere
allegations. More importantly, Petitioners' objection on this subissue
is irrelevant, and therefore immaterial, with regard to EPA's final
tolerance revocation regulation because Petitioners ignored EPA's
extensive analysis of this subissue in the final rule and refiled their
comments on the proposal as if EPA's determination in the final rule
did not exist. The statute, however, requires that objections be filed
on the final rule, not on the proposal. By ignoring the EPA's final
rule on this subissue, Petitioners have failed to lodge a relevant
objection. Both EPA and FDA precedent make clear that when the agency
substantively responds to comments on the proposal, the commenter may
only keep that issue alive in its objections by addressing the agency's
substantive response. In other words, the final rule is the focal point
for determining whether issues remain that must be resolved by the
objection and hearing process. Any other approach relegates the notice-
and-comment rulemaking stage of the revocation process to a meaningless
exercise.
Petitioners' objections on this subissue are denied as irrelevant
to the conclusions reached in the final rule. The final rule explains
why Petitioners' arguments are without a basis, and Petitioners have
failed to address that explanation. For essentially the same reasons,
EPA denies the objection.
For essentially the same reasons, EPA denies the hearing request
and objection designated above as Objection/hearing request sub issue:
Technical Flaws in EPA's statistical comparisons. Petitioners'
objection and hearing request on this subissue consist of mere
reiteration of the comments submitted in response to the proposed
tolerance revocation. The final rule explained the reasons that
Petitioners' arguments are flawed, and the objections are denied for
the same reasons.
(vii) Subissue: Is EPA's approach to comparing brain and RBC AChE
inhibition in juveniles due to carbofuran exposure scientifically
valid? Petitioners allege that EPA's approach to calculating the
relative sensitivity between AChE inhibition in brain and RBC in
juveniles is not scientifically valid. EPA derived the ratio of RBC and
brain AChE inhibition using the data on administered dose (measured in
terms of BMD50) for PND11 animals. In addition, the
Petitioners criticize EPA for incorrectly assuming that the
relationship of the dose response curve between BMD50s and
BMD10s is linear, which they claim overstates the potential
differences. In support of the claim that EPA's approach overstates the
differences, Petitioners argue that data suggests that
BMD50s for brain and RBC AChE inhibition for the carbamates
tend to diverge more than the dose levels that cause the low levels of
AChE inhibition used to select the PoD (i.e., the BMD10s),
which demonstrates that at levels causing lower levels of inhibition,
no safety factor is necessary. Petitioners' argument is that the 4X
ratio EPA calculated based on the BMD50 is unnecessarily
protective, because the difference between brain and RBC at the doses
causing lower levels of inhibition (i.e., 10%), which are the levels at
which EPA is regulating, would not be significant.
Petitioners' hearing request on this subissue is denied for two
reasons. First, Petitioners proffered no evidence on any carbamate,
much less carbofuran, in support of their claim that BMD50s
for the carbamates tend to diverge more than the BMD10s or
that the response curve between BMD50s and BMD10s
is not linear. A hearing will not be granted on the basis of mere
allegations. Second, Petitioners' claims are immaterial because unless
Petitioners can show what the relationship is between the response
curves for BMD50s and BMD10s (an assertion they
have not even made), a showing that EPA's assumption of linearity is
incorrect can only force EPA to abandon the 4X children's safety factor
in favor of the default 10X value.
The objection that EPA's modeling is scientifically invalid is
denied. EPA's modeling has been repeatedly reviewed and approved by the
SAP, including most recently with respect to the modeling of
carbofuran's dose-response curves. There is no indication in the
modeling that EPA's assumption of parallel dose-response curves
overstates the difference, and given the absence of data supplied by
Petitioners in support of this objection, the objection is denied.
(viii) Subissue: Did EPA err by combining data from different
toxicological studies in calculating the estimates of BMD50s
that serves as
[[Page 59679]]
quantitative support for derivation of the 4X childrens' safety factor?
In its risk assessment, EPA relied on all of the valid data from the
available studies to calculate the estimates that served as the PoD,
and to calculate BMD50s used in choosing the children's
safety factor. In their comments on the proposed rule, Petitioners
claimed that EPA's decision to combine data for different strains of
rats, sexes, experiments, laboratories, dates, dose preparations, rat
ages, and times between dosing and AChE measurement, is problematic,
claiming that these differences in study design severely limit the
validity of EPA's comparisons and caused EPA to overestimate the
difference between brain and RBC AChE inhibition. EPA responded to
these comments in full during the rulemaking (74 FR 23052-23053; Ref.
85). Petitioners referenced their earlier comments in their objections,
but presented no further evidence on any of these points. Nor in their
objections and request for hearing did Petitioners address EPA's
explanation set forth in the final rule.
A hearing is not appropriate on this subissue because Petitioners
have not challenged the basis EPA asserted in the final rule for
rejecting their concerns nor have they proffered any evidence that
calls the substance of EPA's conclusions into question. A hearing is
not warranted on the basis of mere denials or contentions, nor when the
commenter simply reiterates comments raised in response to the proposed
rule (40 CFR 178.32(b)(1) and (2)). Additionally, this hearing request
is rejected for lack of materiality. If EPA abandoned its sophisticated
analysis of multiple studies and datasets and simply followed the
general approach laid out in its BMD policy, EPA would have chosen a
significantly lower BMD dramatically raising EPA's risk estimates.
Petitioners' objection on this subissue is denied because
Petitioners have not responded to the explanation EPA provided in the
final rule supporting its meta-analysis of multiple studies. Consistent
with Agency guidance, EPA believes that consideration of all available
data is the scientifically more defensible approach, rather than the
selective exclusion of reliable data. Petitioners' objection on this
point is particularly weak given that their analysis also combines
various data sets and only arrives at a higher estimate of the BMD by
selectively excluding, without explanation, the data most pertinent to
assessing carbofuran's acute affects.
b. Drinking Water Exposure Objection--In large part, Petitioners'
objections to EPA's assessment of carbofuran levels in drinking water
are inextricably intertwined with their recently-proposed registration
amendments which attempt to create a scheme whereby carbofuran use
would be limited in individual watersheds. As explained above (see Unit
VI.F.2.a), objections based on these recently-proposed registration
amendments are irrelevant to EPA's determination in the final tolerance
revocation rule. Nonetheless, in Unit VI.F, EPA exhaustively evaluated
all of the arguments put forward in Petitioners' drinking water
objection and explained why a hearing was not appropriate on any of
these arguments and why, on the merits, the arguments were without
basis. Below EPA has summarized its reasoning.
The first four subissues below pertain to EPA's assessment of the
carbofuran groundwater exposure assessment and the last eight address
the surface water assessment. In this regard, it is important to note
that, in order to determine that a tolerance for a particular use will
be safe, EPA must be able to determine that anticipated concentrations
in both surface water and ground water resulting from that use will be
safe.
(i) Subissue: Did EPA err in relying on the results of the
prospective ground water study (PGW) and historical monitoring to
validate groundwater exposure estimate? The Petitioners object that EPA
should not have relied for validation on their PGW study or historical
monitoring data. They argue that these data no longer reflect current
use patterns and that all areas like those seen in the PGW have now
been removed from the carbofuran label.
A hearing is not appropriate on this subissue because the
Petitioners have failed to proffer evidence, which would, if
established, resolve a material issue in their favor. First,
Petitioners fail to take into account the clear record evidence that
EPA scaled the PGW modeling to reflect the lower current use rates.
Second, Petitioners are simply incorrect to claim that EPA
``validated'' its quantitative groundwater assessment based on historic
monitoring data that are not reflective of current application rates.
The targeted monitoring data used for validation were based on
application rates that are identical or lower than the current use
rates. Third, the majority of Petitioners' evidence is untimely, and to
the extent Petitioners' are claiming that the PGW and other targeted
monitoring data are not reflective of FMC's June 29, 2009 proposed
registration amendments, that claim is irrelevant to the current
proceeding. Finally, Petitioners' evidentiary proffer on the PGW is
internally contradictory given that Petitioners' own experts relied on
the PGW to validate the modeling submitted in support of this
objection.
The objection on this subissue is denied because timely evidence
and reasoning submitted by Petitioners is contradictory, non-probative,
or flatly contradicted by the record.
(ii) Subissue: Does EPA's assessment of carbofuran levels in ground
water account for all of FMC's label mitigation measures and ``rely on
unrealistic and overly conservative assumptions about potential
concentrations''? In this objection, the Petitioners allege that
maximum concentrations of carbofuran in groundwater are expected to be
below 1.1 ppb, based on their proposed geographic restrictions and well
setbacks. EPA believes Petitioners' objection and hearing request on
this subissue is inextricably intertwined with FMC's recently-submitted
FIFRA registration amendments and thus the objection is denied as
irrelevant on that account.
Nonetheless, to the extent possible EPA has attempted to evaluate
this objection based on the label mitigation measures submitted and
adopted prior to issuance of the final tolerance revocation rule and
ruled on it on that basis. EPA denies the objection and its associated
hearing request because Petitioners have again failed to object to
EPA's final rule. It is clear from the record that EPA's final rule and
risk assessment did account for all of the risk mitigation measures
submitted as part of the September 2008 comments. Petitioners have not
raised any substantive challenge to the manner in which EPA's modeling
addressed those measures. In addition, Petitioners' objections provide
no further clarification as to what is meant by their claim that EPA's
assessment relied on ``unrealistic and overly conservative
assumptions.'' Therefore, this objection, and the attendant hearing
request, is denied based on Petitioners' failure to state with
``particularity * * * the basis for the objection * * *.''(40 CFR
178.25(a)(2)). As Petitioners raised similar allegations in their
comments, EPA has assumed that they intended to incorporate all of the
issues raised in the comments on the proposed rule. However, EPA
addressed these assertions in the final rule. Because Petitioners have
once again ignored the explanations provided in the final rule, this
objection and hearing request are denied as immaterial.
(iii) Subissue: Is EPA's assessment of the levels of carbofuran in
groundwater appropriate given the manner in which
[[Page 59680]]
EPA assessed groundwater exposures in the NMC CRA? Petitioners object
that EPA's estimates in the final rule are inconsistent with the
groundwater concentration estimates EPA developed for the NMC CRA.
However, they do not identify any specific inconsistency, they simply
make the general allegation. They allege that, by contrast, their
assessment, which estimated maximum concentrations of 1.1 ppb, is
consistent with the NMC CRA.
EPA denies the request for a hearing on this sub-issue because
there is no disputed factual matter for resolution (i.e., the manner in
which EPA assessed groundwater exposure for carbofuran and for the NMCs
is a matter of record); rather, the objection poses the legal question
of whether it was appropriate for EPA to assess groundwater exposure
for carbofuran and the NMCs in a different manner. Further, because
Petitioners have not identified any specific inconsistency between the
two groundwater exposure assessments, it constitutes nothing more than
a mere allegation or denial. As EPA's regulations make clear, a mere
``denial'' of an EPA position is not sufficient to satisfy the standard
for granting a hearing (40 CFR 178.32(b)(2)). Finally, the claim that
their modeling is consistent with the NMC CRA does not justify a
hearing on this question. As EPA explained in the final rule, the
values estimated in the modeling conducted for the NMC CRA are greater
than the 1.1 ppb level that FMC claims is the maximum expected 1-in-10-
year peak concentration. A hearing is not warranted where the claim is
clearly contradicted by the record (40 CFR 178.32(b)(2)).
On the merits, Petitioners' objection is denied because the results
of Petitioners' groundwater assessment are not consistent with the
estimates developed for the NMC CRA. The NMC CRA examined carbofuran at
two sites, northeast Florida and the Delmarva Peninsula. In Florida,
concentrations were found to be below levels of concern because of high
pH, but in Delmarva, both in corn and in melon scenarios EPA estimated
that 90% of daily concentrations could be as high as 20.5 and 25.6 ppb,
respectively. These values are far greater than the 1.1 ppb that
Petitioners claim is the maximum expected 1-in-10-year peak
concentration.
(iv) Did EPA err in not using PCT data in assessing surface water
exposure? The Petitioners object to the assumption in the surface water
assessments in the final rule that 100% of the crops in a watershed
will be treated with carbofuran. The Petitioners argue that actual
carbofuran sales data on a county basis from 2002-present demonstrate
that the current carbofuran PCT is less than 4.25%. Using this PCT, and
taking into account the recently submitted ``no application buffers,''
the Petitioners allege that the modeling in Exhibit 15 demonstrates
that carbofuran concentrations in surface water will not exceed 1.1
ppb, ``which is below the level of concern.'' In support of this
objection, the Petitioners reference county level sales data that were
submitted to the Agency after the close of the comment period. They
also reference the use tracking system proposed in their recent
registration amendments (Exhibit 2) and the modeling contained in
Exhibit 15. Because this subissue is inextricably intertwined with
Petitioners' recently-proposed FIFRA registration amendments, it is
denied as irrelevant.
To the extent Petitioners' objection on this subissue is limited to
EPA's refusal to use a 4% PCT in estimating drinking water
concentrations in individual watersheds based on the information
provided as part of their comments on the proposed rule, this objection
and hearing request are also denied as immaterial. The Petitioners have
failed to respond to EPA's explanation in the final rule that the
information and methodology on which they relied to estimate a 4% PCT
was fundamentally flawed, and to submit any evidence calling the basis
of EPA's response into question (40 CFR 178.32(b)(3)). Additionally,
the proffered evidence here is untimely. The sales data and methodology
used to generate use estimates, as well as the modeling in Exhibit 15,
were not submitted during the comment period on the proposed rule even
though the information was clearly available to Petitioners (40 CFR
178.32(b)(2)).
Petitioners' objection on this subissue is denied because the
proffered evidence is untimely and, even if considered, insufficient.
Although EPA does use reliable data on pesticide usage in estimating
exposure levels in food, this approach has limited applicability in
drinking water assessments due to the differences in the sources of
food and water for consumers. The food market in the United States is
national in scope but the sources of drinking water are primarily
local. Thus, while differences in the usage of pesticides across the
country will average out in estimating pesticide exposure from food,
such averaging is not applicable to estimating pesticide exposure in
drinking water--i.e., a person's drinking water exposure is generally
always from the same watershed. Moreover, the information that
Petitioners submitted on PCT was not usage data--the type of
information normally used in estimating PCT for food--but sales data.
The link between sales data and the location of use is tenuous. Given
that EPA lacks the information to allow EPA to generally use PCT
information in estimating drinking water exposure, and the poor quality
of information Petitioners submitted on usage (i.e. county-level sales
data), EPA concludes it could not make an exposure estimate on
carbofuran in drinking water with sufficient confidence to meet the
FFDCA's reasonable certainty of no harm standard.
(v) Subissue: Do the results of FMC surface water modeling
establish that carbofuran levels will not exceed 1.1 ppb? The
Petitioners claim that the prior surface water assessments submitted to
the Agency and a new assessment incorporating FMC's newly-proposed
FIFRA registration amendments demonstrate that carbofuran
concentrations in surface water are not expected to exceed 1.1 ppb.
Because this subissue is inextricably intertwined with Petitioners'
recently-proposed FIFRA registration amendments, it is denied as
irrelevant. Nonetheless, EPA has carefully evaluated all of
Petitioners' allegation to determine if any of their claims meet the
standard for a hearing or are otherwise meritorious.
A hearing is also denied on this sub-issue because Petitioners'
objection on this subissue is irrelevant, and therefore immaterial,
with regard to EPA's final tolerance revocation regulation. Petitioners
have not responded to EPA's extensive analysis of these studies, which
included an explanation for the Agency's conclusion that they were
significantly flawed, presented in the final rule. The statute,
however, requires that objections be filed on the final rule not the
proposal. By ignoring EPA's final rule on this subissue, Petitioners
have failed to lodge a relevant objection. Both EPA and FDA precedent
make clear that when the agency substantively responds to comments on
the proposal, the commenter may only keep that issue alive in its
objections by addressing the agency's substantive response (40 CFR
178.32(b)(3)). Similarly, the Petitioners' new assessment directly
relies on FMC's newly-proposed FIFRA registration amendments and is
thus irrelevant to this proceeding. Their new assessment is also
untimely in that it primarily appears to be a fuller description of
Petitioners' National CWS Assessment, which was described, but not
provided as part of their comments on the proposed rule (40 CFR
178.32(b)(2)).
[[Page 59681]]
EPA has outlined the substantial flaws in the previously-submitted
assessments in the final tolerance revocation rule and in Unit VI.F,
above. For the all the reasons cited therein, this objection is denied.
(vi) Did EPA inappropriately rely on NAWQA monitoring data in
assessing carbofuran levels in surface water? The Petitioners object to
EPA's discussion in the final rule of the high concentrations detected
in Zollner Creek in Oregon and claim that EPA inappropriately relied on
NAWQA monitoring data in estimating surface water exposure levels of
carbofuran. A hearing on this issue is denied because there are no
material factual issues in dispute. The extent to which EPA discussed
the Zollner Creek data as part of its discussion of monitoring results
from all other NAWQA sites, SDWA post-treatment monitoring, and the
results of field studies is clear on the record. The record is also
clear regarding the degree of reliance EPA placed on monitoring data in
estimating carbofuran levels in surface water. The objection on this
subissue is denied because it was reasonable for EPA to consider NAWQA
data in assessing the likelihood that carbofuran residues may be
present in surface water. Moreover, the record is clear that, even
though EPA considered the NAWQA data, it placed primary emphasis on the
carbofuran levels detected in post-treatment SDWA monitoring.
(vii) Should EPA consider FMC's newly-proposed terms of
registration for carbofuran? The objection is denied because it is
based on FMC's newly proposed revisions to its carbofuran registration
that were submitted after publication of the final tolerance revocation
rule and is thus irrelevant to this proceeding. An additional ground
for denial of this objection and hearing request is that Petitioners
proferred no evidence to support their allegation that these proposed
requirements would be effective in limiting carbofuran exposure to the
extent claimed
(viii) Should EPA have used the NMC CRA surface water estimates in
assessing exposure to carbofuran in surface water? Petitioners object
to EPA's surface water exposure estimates on the ground that they are
inconsistent with the estimates EPA developed for purposes of the NMC
CRA. This hearing request is denied because there are no factual
matters in dispute; rather, the only question is a legal one of whether
it was inappropriate for EPA to use different approaches to assessing
surface water exposure for the carbofuran surface water assessment and
the cumulative assessment of surface water exposure for NMCs (40 CFR
178.32(b)(1)). In addition, this issue was raised in Petitioners'
comments on the proposed revocation. In the final revocation, EPA
explained how the substantial differences between a cumulative risk
assessment for a class of pesticides and a risk assessment for a single
pesticide necessitate different approaches. Petitioners have not
challenged the substance of EPA's response to their comments or
submitted evidence that calls the substance of EPA's final rule
conclusions into question, and the objection and associated hearing
request is therefore immaterial (40 CFR 178.32(b)(3)). Finally, on
multiple grounds, Petitioners' evidentiary proffer is insufficient to
support a conclusion that there is a reasonable possibility that the
issue could be resolved in their favor. Petitioners' objection on this
subissue is denied for essentially the same reasons explained in the
final tolerance revocation.
(ix) Has EPA taken natural surface water pH conditions into
account? The Petitioners contend that the PCT levels guaranteed by the
recently proposed use tracking system, along with natural surface water
pH conditions in the areas included under the revised label will ensure
that potential exposures are de minimis. Because this objection is
inextricably intertwined with FMC's newly-proposed FIFRA registration
amendments, it is denied as irrelevant to this proceeding.
Even assuming Petitioners' allegation concerning soil pH can be
separated from the proposed registration amendments, Petitioners'
claims are insufficient to justify the action urged (40 CFR
178.32(b)(3)). Petitioners admit that their pH analyses explicitly only
capture 95% of surface waters. Because EPA cannot ignore the other 5%
of surface water, this information, even if established, would provide
an insufficient basis on which EPA could reasonably conclude that the
drinking water exposures would be ``safe.'' Additionally, the proffered
evidence for this objection is untimely because although the effects of
pH were clearly discussed in the proposed rule, Petitioners' claim and
the analyses supporting it were not submitted during the comment
period.
For the same reasons, the Petitioners' objection is denied.
(x) Has EPA taken the effect of existing drinking water treatment
systems into account? The Petitioners contend that, in the areas where
carbofuran use is allowed under revised labels, the majority of the
total population is protected from carbofuran by water treatment
systems and that the rest of the population is protected by
Petitioners' newly-proposed FIFRA registration amendments. Because this
objection is inextricably intertwined with FMC's newly-proposed FIFRA
registration amendments, it is denied as irrelevant to this proceeding.
Separating out the allegations that are independent from the new
registration amendments, EPA denies this hearing request on the grounds
that Petitioners' claims are insufficient to justify the action urged
(40 CFR 178.32(b)(3)) in that they would fail to justify a conclusion
that the carbofuran tolerances are safe. The fact that the majority of
people are protected is irrelevant if major identifiable subpopulations
are not. Further, both the objection and the proffered evidence are
untimely because Petitioners' claims and analyses supporting them were
not submitted during the comment period. For the same reasons, this
objection is denied.
c. Recovery Time Objection--(i) Subissue: Has EPA overstated risk
through its approach to considering recovery time to the effects of
carbofuran? For carbofuran, EPA estimated acute dietary exposure for
the acute risk assessment by summing exposure over a 24-hour period.
Because humans are likely to recover in a relatively short time period
from any single carbofuran exposure, EPA also undertook a more
sophisticated exposure assessment that took recovery time into effect.
This more sophisticated analysis was not substituted for the 24-hour
assessment approach but rather was used to evaluate whether the 24-hour
approach substantially overstated risk. The reason for not simply
adopting the assessment incorporating recovery time was based on
concerns that other aspects of its exposure model tend to understate
exposure. If the assessment using recovery time had suggested that
carbofuran risks may be acceptable, EPA would have further examined how
exposure should be assessed. However, because both the assessment based
on 24-hour exposure and the one incorporating recovery time showed
carbofuran exposures significantly exceed the safe level, EPA concluded
that its exposure assessment was reasonable. Further supporting this
conclusion was the fact that various other analyses showed that a
single eating occasion could result in excessive risk to infants.
Petitioners have objected to this approach claiming that recovery time
should be included in EPA's ``primary'' risk assessment.
EPA is denying this hearing request on two grounds. First, the
objection fails
[[Page 59682]]
to present a disputed issue of material fact because EPA did
incorporate recovery time into its analysis. Rather, Petitioners' only
challenge is to whether EPA should have only presented risk estimates
that accounted for recovery. This is a policy issue, and hearings are
not appropriate on such (40 CFR 178.32(b)(1)).
Second, the fact that EPA relied on 24-hour aggregate exposures in
addition to analyses that accounted for recovery is not material,
because even though accounting for recovery resulted in a 2-3X
reduction in exposure estimates, many of EPA's estimates for aggregate
exposures ranged between 2700% aPAD and 9400% aPAD for infants.
Accounting for recovery does not, therefore, demonstrate that aggregate
exposures will be safe for infants. Of greater significance in this
regard is EPA's finding that infants are at risk from a single
exposure. Recovery is only relevant, by definition, where the risk is
derived from multiple exposures over time.
Petitioners' objection to EPA's policy decision to present acute
risks in terms of 24 hours of exposure is denied because EPA's policy
approach here is reasonable. For the reasons explained in Unit VI.G,
there are several factors that may cause EPA's exposure/risk model to
either understate or overstate exposure/risk. It is unreasonable to
present risks only incorporating factors that tend to reduce exposure/
risk estimates (e.g., recovery time), as Petitioners suggest. EPA's
approach of evaluating the impact that these factors may have on the
risk assessment is an appropriate method of taking all relevant factors
into account.
(ii) Subissue: Did EPA err in calculating carbofuran half-lives? In
the proposed rule, EPA used half-lives of 150 minutes and 300 minutes,
based on calculations derived for the NMC CRA. In the final rule, EPA
calculated half-lives specific to carbofuran to ensure that its
analyses accurately reflected carbofuran's risk. Petitioners contend
that EPA's calculation of carbofuran half-lives of 186 minutes and 426
minutes were flawed, and that the data instead support the use of a
150-minute half-life.
Petitioners' hearing requests on this subissue are denied for two
reasons. First, Petitioners have not provided the underlying analyses
conducted in support of their claims that the appropriate half-life for
carbofuran is 150 minutes, rather than the 186 or 426 minutes that EPA
calculated. Petitioners' evidentiary proffer thus consists of no more
than mere allegations and denials. Hearings will not be granted on this
basis (40 CFR 178.32(b)(2)).
Further, the issue of the appropriate half-lives for carbofuran is
not material. Petitioners have proffered no evidence to show that
reliance on a 150-minute half-life rather than a 186-minute half-life
would make a significant difference to their estimates. By contrast, in
the risk assessment supporting the final rule, EPA's estimates show
that the use of a 150-minute or 186-minute half-life makes little or no
difference. In addition, EPA's final risk assessment found that infants
are at risk from a single exposure. Recovery is only relevant, by
definition, where the risk is derived from multiple exposures over
time.
EPA denies Petitioners' objection on this subissue because the
evidence submitted fails to establish their allegations, or to rebut
the data and analyses discussed in the final rule.
d. Human Study Objection--Issue: Did EPA reasonably conclude that a
human toxicity study with carbofuran was barred from EPA consideration
by the Human Research Rule? In conducting its dietary risk assessment
for carbofuran, EPA relied on toxicity data conducted with rats, and
applied the default 10X interspecies factor to account for the
potential uncertainty in extrapolating from animal data to humans.
Petitioners object to the decision to use a 10X interspecies factor
claiming that data from a human toxicity study (Arnold) provides a
basis for reducing this factor to 3X. However, EPA has previously
determined that the Arnold study lacks scientific validity and thus may
not be considered by the Agency under EPA's Human Research rule. That
decision was based on the advice of the HSRB, which found the Arnold
study to constitute ``poor science'' (Ref. 38 at 11).
Although Petitioners have made a number of arguments in support of
adopting a 3X interspecies factor, all of the arguments rely on
consideration of the Arnold study. Thus, as a preliminary matter,
Petitioners must show that a hearing is appropriate based exclusively
on whether EPA erred in determining that the Arnold study cannot be
considered under the Human Research rule or, that even if a hearing is
not warranted, that EPA's decision under the Human Research rule was
incorrect.
Petitioners have proffered no evidence that merits a hearing on
EPA's application of the Human Research rule to the Arnold study. As an
evidentiary proffer, Petitioners claim (1) that review of the Arnold
study under the Human Research rule was too narrow in that it did not
consider the Arnold study in light of the animal data; (2) that
insufficient weight was given prior independent reports on the value of
the Arnold study; (3) that the ``technical'' concerns raised by the
HSRB are addressed by ``the data within the study'' and that these
``technical'' deficiencies do not render the Arnold study unreliable.
The first proffer is not material because the availability of animal
data does not address the validity of the Arnold human study. At
bottom, this issue involves a challenge to the policy underlying the
Human Research rule that allows only limited consideration of human
toxicity studies. A hearing is not appropriate on such a policy issue,
nor on the Human Research rule itself. Petitioners' second proffer is a
legal/policy question regarding the weight to be accorded to existing
peer review reports. No hearing is required on such issues. To the
extent the third proffer even constitutes a proffer of ``evidence,'' it
fails because it is nothing more than a mere allegation. Petitioners
have supplied no information as to how the HSRB's ``technical''
concerns are resolved by the study itself.
Viewed on their merits, these claims do not convince EPA that it
erred in determining that the Arnold study did not meet the Human
Research rule because it lacked scientific validity. EPA concluded,
based on the advice of the HSRB, that, because the Arnold study had an
extremely small sample size (2 persons per dose) and highly variable
measurement of RBC and plasma AChE, it had no scientific value. The
claim by Petitioners that somehow the Arnold study could be
rehabilitated by considering it in the context of carbofuran animal
data misunderstands the issue. The question under the Human Research
rule is whether the human study at issue is scientifically valid. Here,
EPA found the Arnold study to be flawed at its core. Animal data on
carbofuran are simply irrelevant to the problems with sample size and
AChE measurement in the Arnold study. As to the earlier reports on the
Arnold study, Petitioners have provided no reason as to why these
should outweigh the HSRB's conclusion concerning whether the Arnold
study met the Human Research rule standard. The earlier reports were
completed well before the Human Research rule was promulgated and thus
could not have addressed the rule's requirements. Further, the earlier
reports identified the same defects, but concluded that the Arnold's
study's flaws could be addressed by the use of additional safety
[[Page 59683]]
factors--an option not available under the Human Research rule. In such
circumstances, it was reasonable for EPA to give primary weight to the
HSRB findings. Petitioners' claim that the HSRB only identified
``technical'' problems with the Arnold study and that the study itself
addresses the HSRB's concerns is without basis. The flaws in the Arnold
study are not technical but fundamental, and cannot be explained away.
Finally, Petitioners' allegations that EPA hampered the HSRB's
consideration of the prior peer review reports and that EPA's recusal
decision was somehow improper are contradicted by the record.
Accordingly, the objection is denied.
e. Import Tolerance Objection--Issue: Did EPA err by failing to
retain the carbofuran tolerances that apply solely to imported food.
Whether EPA had some type of independent duty to retain carbofuran
tolerances for the imported foods bananas, rice, coffee, and sugarcane
despite its finding that aggregate exposure to carbofuran is unsafe, is
a legal question. Hearings are not held on legal issues. Having found
that aggregate exposure to carbofuran is unsafe, EPA was clearly
warranted, if not required, to revoke all tolerances. For the policy
reasons identified above, (see Unit VI.I), when aggregate risk to a
pesticide is unsafe, EPA defers to interested parties to decide in the
first instance what tolerances, if any, they wish to retain. Although
explicitly invited to do so, no person submitted a comment on the
proposed revocation that identified the import tolerances as a subset
of tolerances that were asserted to be safe, and that the commenter
wished to retain. Accordingly, this objection is denied.
K. Conclusion
For all of the reasons set forth above, EPA denies the Petitioners'
objections and their requests for a hearing on those objections.
VII. Regulatory Assessment Requirements
As indicated previously, this action announces the Agency's final
order regarding objections filed under section 408 of FFDCA. As such,
this action is an adjudication and not a rule. The regulatory
assessment requirements imposed on rulemaking do not, therefore, apply
to this action.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, (5 U.S.C. 801 et seq.), as added by
the Small Business Regulatory Enforcement Fairness Act of 1996, does
not apply because this action is not a rule for purposes of 5 U.S.C.
804(3).
IX. References
EPA has established an official record for this rulemaking. The
official record includes all information considered by EPA in
developing this proposed rule including documents specifically
referenced in this action and listed below, any public comments
received during an applicable comment period, and any other information
related to this action, including any information claimed as CBI. This
official record includes all information physically located in docket
ID number EPA-HQ-OPP-2005-0162, as well as any documents that are
referenced in the documents listed below or in the docket. The public
version of the official record does not include any information claimed
as CBI.
Objections to the Final Order Revoking Tolerances for Carbofuran,
and Request for Public Evidentiary Hearing, submitted by National
Potato Council, National Corn Growers Association, National Cotton
Council, National Sunflower Association, and FMC Corporation. June 30,
2009. EPA-HQ-OPP-2005-0162-0578.
Exhibit 1
FMC's letter of 9-29-08 and accompanying label amendments.
Exhibit 2
FMC's letter of 12-24-08 and accompanying label
amendments.
Exhibit 3
FMC's letter of 6-30-09 and accompanying label amendments.
Exhibit 4
Expert Report: Carbofuran's FQPA Safety Factor and
Interspecies Uncertainty Factor by K. Wallace (6 p.)
13 published articles on pesticide effect on
cholinesterase activity.
Exhibit 5
Central Nervous System as the Primary Target for
Carbofuran's Effects on Lip Smacking by Neal, Williams, & Lamb (3 p.)
10 published articles on effects of cholinergic
stimulation.
Exhibit 6
Expert Report: Carbofuran FQPA Safety Factor by K. Wallace
(8 p.)
9 published articles on HBC versus brain cholinesterase
inhibition.
Exhibit 7
Dose Response Modeling Issue in Carbofuran by Sielken:
AChE and BMD Ratios
Exhibit 8
Dose Response Modeling Issue in Carbofuran by Sielken:
Statistical Comparison of AChE Inhibition in RBC and Brain in Rats
Exposed to Carbofuran.
Exhibit 9
Dose Response Modeling Issue in Carbofuran by Sielken:
OPP's Estimates of the Half-Life of AChE Recovery.
Exhibit 10
Reiner, 1971. Spontaneous Reactivation of Phosphorylated
and Carbamylated Cholinesterases Bulletin WHO 44, 109-112.
Exhibit 11
Carbofuran Dietary Risk Assessment. 2009. (Exponent Inc.,
for FMC)
Exhibit 12
Williams, Cheplick, Engle, Fawcett and Hoogeweg. 2009.
National Carbofuran Leaching Assessment. Vol 1. Waterborne
Environmental Inc., Engel Consulting, and Fawcett Consulting for FMC.
Exhibit 13
Williams, Cheplick, Engle, Fawcett and Hoogeweg. 2009.
National Carbofuran Leaching Assessment. Vol 2. Setback Analysis.
Waterborne Environmental Inc., Engel Consulting, and Fawcett Consulting
for FMC.
Exhibit 14
Memorandum. From: Hoogeweg and Williams, Waterborne, Inc.,
To: Fuge, Latham and Watkins, LLP. June 30, 2009. Subject: Groundwater
pH in selected states.
Exhibit 15
Williams, Fawcett and Engle. 2009. The Development and
Evaluation of a Carbofuran Management Plan to Protect Drinking Water
Derived from Surface Water Sources. Waterborne Environmental Inc., for
FMC.
Exhibit 16
Memorandum. From: Hoogeweg and Williams, Waterborne, Inc.,
To: Fuge, Latham and Watkins, LLP. June 30, 2009. Subject: Surface
water pH in selected states.
Exhibit 17
Memorandum. From: Williams, Waterborne, Inc., To: Fuge,
Latham and Watkins, LLP. June 30, 2009. Subject: Water Treatment
Assessment in Carbofuran Use States.
[[Page 59684]]
Exhibit 18
Petition of the National Corn Grower's Association, the
National Sunflower Association, the National Potato Council, and FMC
Corporation to Defer the Effective Date of Certain Tolerance
Revocations for Carbofuran.
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2. Acute oral (gavage) time course study and final report of
cholinesterase depression from carbofuran technical in adult and
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(unpublished FMC studies) EPA-HQ-OPP-2007-1088-0063 and -0066.
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List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: October 30, 2009.
Debra Edwards,
Director, Office of Pesticide Programs.
[FR Doc. E9-27261 Filed 11-17-09; 8:45 am]
BILLING CODE 6560-50-P