[Federal Register Volume 73, Number 148 (Thursday, July 31, 2008)]
[Proposed Rules]
[Pages 44864-44892]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-17660]
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Part III
Environmental Protection Agency
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40 CFR Part 180
Carbofuran; Proposed Tolerance Revocations; Proposed Rule
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 /
Proposed Rules
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2005-0162; FRL-8373-8]
Carbofuran; Proposed Tolerance Revocations
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA is proposing to revoke all tolerances for carbofuran. The
Agency has determined that the risk from aggregate exposure from the
use of carbofuran does not meet the safety standard of section
408(b)(2) of the Federal Food, Drug, and Cosmetic Act (FFDCA). EPA is
specifically soliciting comment on whether there is an interest in
retaining any individual tolerance, or group of tolerances, and whether
information exists to demonstrate that such tolerance(s) meet(s) the
FFDCA section 408(b)(2) safety standard. EPA encourages interested
parties to comment on the tolerance revocations proposed in this
document and on the proposed time frame for tolerance revocation.
Issues not raised during the comment period may not be raised as
objections to the final rule, or in any other challenge to the final
rule.
DATES: Comments must be received on or before September 29, 2008.
ADDRESSES: Submit your comments, identified by docket identification
(ID) number EPA-HQ-OPP-2005-0162, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Building), 2777 S. Crystal Drive, Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket telephone number is (703) 305-5805.
Instructions: Direct your comments to docket ID number EPA-HQ-OPP-
2005-0162. EPA's policy is that all comments received will be included
in the docket without change and may be made available on-line at
http://www.regulations.gov, including any personal information
provided, unless the comment includes information claimed to be
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Do not submit information that you
consider to be CBI or otherwise protected through regulations.gov or e-
mail. The Federal regulations.gov website is an ``anonymous access''
system, which means EPA will not know your identity or contact
information unless you provide it in the body of your comment. If you
send an e-mail comment directly to EPA without going through
regulations.gov, your e-mail address will be automatically captured and
included as part of the comment that is placed in the docket and made
available on the Internet. If you submit an electronic comment, EPA
recommends that you include your name and other contact information in
the body of your comment and with any disk or CD-ROM you submit. If EPA
cannot read your comment due to technical difficulties and cannot
contact you for clarification, EPA may not be able to consider your
comment. Electronic files should avoid the use of special characters,
any form of encryption, and be free of any defects or viruses.
Docket: All documents in the docket are listed in the docket index.
Although listed in the index, some information is not publicly
available, e.g., 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 either 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
Building), 2777 S. Crystal Drive, Arlington, VA. The hours of operation
of this Docket Facility are from 8:30 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays. The Docket telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Jude Andreasen Special Review and
Reregistration Division (7508C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave, NW.,
Washington, DC 20460-0001; telephone number: (703) 305-0076; e-mail
address: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
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. To determine
whether you or your business may be affected by this action, you should
carefully examine the applicability provisions in [Unit II.A]. 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. What Should I Consider as I Prepare My Comments for EPA?
1. Submitting CBI. Do not submit this information to EPA through
regulations.gov or e-mail. Clearly mark the part or all of the
information that you claim to be CBI. For CBI information in a disk or
CD ROM that you mail to EPA, mark the outside of the disk or CD ROM as
CBI and then identify electronically within the disk or CD ROM the
specific information that is claimed as CBI. In addition to one
complete version of the comment that includes information claimed as
CBI, a copy of the comment that does not contain the information
claimed as CBI must be submitted for inclusion in the public docket.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2.
2. Tips for preparing your comments. When submitting comments,
remember to:
i. Identify the document by docket ID number and other identifying
information (subject heading, Federal Register date and page number).
ii. Follow directions. The Agency may ask you to respond to
specific questions or organize comments by referencing a
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Code of Federal Regulations (CFR) part or section number.
iii. Explain why you agree or disagree; suggest alternatives and
substitute language for your requested changes.
iv. Describe any assumptions and provide any technical information
and/or data that you used.
v. If you estimate potential costs or burdens, explain how you
arrived at your estimate in sufficient detail to allow for it to be
reproduced.
vi. Provide specific examples to illustrate your concerns and
suggest alternatives.
vii. Explain your views as clearly as possible, avoiding the use of
profanity or personal threats.
viii. Make sure to submit your comments by the comment period
deadline identified.
C. What Can I Do if I Wish the Agency to Maintain a Tolerance that the
Agency Proposes to Revoke?
This proposed rule provides a comment period of 60 days for any
interested person to submit comments on the Agency's proposal. EPA
issues a final rule after considering comments that are submitted in
response to this proposed rule. Comments should be limited only to the
pesticide and tolerances subject to this proposed notice.
EPA's finding that aggregate exposure from all 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. For example, in its Interim Reregistration
Eligibility Decision (IRED), EPA concluded that the Agency could
maintain import tolerances for bananas, coffee, rice, and sugarcane,
because dietary risks from the food residues from the import tolerances
are below the Agency's level of concern when considered together with
the food residues from the phase-out crops, but with no other domestic
uses (Ref. 35). However, as discussed in more detail below, EPA can
only maintain tolerances that it can determine will be ``safe'' within
the meaning of section 408(b)(2)(A)(ii). Accordingly, commenters
interested in retaining any tolerance or group of tolerances should
consider submitting information to demonstrate that the tolerance(s)
meet the statutory standard, rather than merely indicating an interest
in retaining the tolerance. Commenters should also be aware that even
if EPA determines that any carbofuran tolerance(s) meet the safety
standard, those tolerances can only be maintained if EPA can also
determine that the cumulative effects from those tolerances, when
considered with the exposures from other N-methyl carbamate pesticide
chemicals, will meet the FFDCA 408(b)(2) safety standard. EPA will not
respond to any comments on subjects that do not relate to the
evaluation or safety of the pesticide tolerances subject to this
proposed notice.
After consideration of comments, EPA will issue a final regulation
determining whether revocation of the tolerances is appropriate and
making a final finding on whether these tolerances are ``safe'' within
the meaning of section 408(b)(2)(A)(ii). Such regulation will be
subject to objections pursuant to section 408(g) (21 U.S.C. 346a(g)).
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.
II. Introduction
A. What Action is the Agency Taking?
EPA is proposing to revoke all of the existing tolerances for
residues of carbofuran. Currently, tolerances have been established on
the following crops: alfalfa, fresh; alfalfa, hay; artichoke, globe;
banana; barley, grain; barley, straw, sugar beet; sugar beet, tops;
coffee bean; corn, forage; corn, fresh (including sweet corn); corn,
grain (including popcorn); corn, stover; cotton, undelinted seed;
cranberry; cucumber; grape; grape (raisin); melon; milk; oat, grain;
oat, straw; pepper; potato; pumpkin; raisins, waste; rice, grain; rice,
straw; sorghum, fodder; sorghum, forage; sorghum, grain; strawberry;
soybean; soybean, forage; soybean, hay; squash; sugarcane, cane;
sunflower, seed; wheat, grain; wheat, straw. The Agency is proposing to
revoke tolerances for these crops because aggregate dietary exposure to
residues of carbofuran, including all anticipated dietary exposures and
all other exposures for which there is reliable information, is not
safe.
EPA has determined that aggregate exposure to carbofuran greater
than 0.000075 mg/kg/day (i.e., greater than the acute Population
Adjusted Dose (aPAD)) does not meet the safety standard of section
408(b)(2) of the FFDCA. Based on the contribution from food alone, the
more sensitive children's subpopulations receive unsafe exposures to
carbofuran. At the 99.9th percentile of exposure, aggregate carbofuran
dietary exposure from food alone was estimated to range between
0.000121 mg/kg/day for children 6-12 (160% of the aPAD) and 0.000156
mg/kg/day (210% of the aPAD) for children 3-5 years old, the population
subgroup with the highest estimated dietary exposure. In addition,
EPA's analyses show that those individuals-both adults and children--
who receive their drinking water from vulnerable sources are also
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 groundwater from shallow wells in acidic
aquifers overlaid with sandy soils that have had crops treated with
carbofuran. Aggregate exposures from food and from drinking water
derived from ground water in vulnerable areas (i.e., from shallow wells
associated with sandy soils and acidic aquifers, such as are found in
the Delmarva Peninsula of Delaware, Maryland, and Virginia) result in
even higher estimated exceedances. The aggregate estimates for food and
ground water exposure range between 1100% of the aPAD for adults over
50 years, to over 10,000% of the aPAD for infants. Similarly, EPA
analyses show substantial exceedances for those populations that obtain
their drinking water from reservoirs (i.e., surface water) located in
small agricultural watersheds, prone to runoff, and predominated by
crops that are treated with carbofuran, even though there is more
uncertainty associated with these exposure estimates. For example,
estimated aggregate exposures from food and drinking water derived from
surface water, based on the corn use in Nebraska, range between 340% of
the aPAD for youths 13-19, and 3900% of the aPAD for infants.
Every sensitivity analysis EPA has performed has shown that
estimated exposures (both for food alone as well as for food and water)
significantly exceed EPA's level of concern for children. Although the
magnitude of the exceedance varies depending the level of conservatism
in the assessment, the fact that in each case aggregate exposures from
carbofuran fail to meet the FFDCA section 408(b)(2) safety standard,
including where EPA relied on highly refined estimates of risk,
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using all relevant data and methods, strongly corroborates EPA's
conclusion that aggregate exposures from carbofuran are not safe.
B. What is the Agency's authority for Taking this Action?
EPA is taking this action, pursuant to the authority in FFDCA
sections 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).
III. Statutory and Regulatory Background
A ``tolerance'' represents the maximum level for residues of
pesticide chemicals legally allowed in or on raw agricultural
commodities (including animal feed) and processed foods. Section 408 of
the FFDCA, 21 U.S.C. 346a, as amended by the Food Quality Protection
Act (FQPA) of 1996, Public Law 104-170, authorizes the establishment of
tolerances, exemptions from tolerance requirements, modifications in
tolerances, and revocation of tolerances for residues of pesticide
chemicals in or on raw agricultural commodities and processed foods.
Without a tolerance or exemption, food containing pesticide residues is
considered to be unsafe and therefore ``adulterated'' under section
402(a) of the FFDCA, 21 U.S.C. 342(a). Such food may not be distributed
in interstate commerce (21 U.S.C. 331(a)). For a food-use pesticide to
be sold and distributed, the pesticide must not only have appropriate
tolerances under the FFDCA, but also must be registered under the
Federal Insecticide Fungicide and Rodenticide Act (FIFRA) (7 U.S.C. 136
et seq.). Food-use pesticides not registered in the United States must
have tolerances in order for commodities treated with those pesticides
to be imported into the United States.
Section 408(e) of the FFDCA, 21 U.S.C. 346a(e), authorizes EPA to
modify or revoke tolerances on its own initiative. EPA is proposing to
revoke these tolerances to implement the Agency's findings made during
the reregistration and tolerance reassessment processes. As part of
these processes, EPA is required to determine whether each of the
existing tolerances meets the safety standard of section 408(b)(2) (21
U.S.C. 346a(b)(2)). 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)(i)). 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.
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; and
(III) available information concerning the cumulative effects on
infants and children of such residues and other substances that have
a common mechanism of toxicity. ...
(21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)).
This provision further 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 proposal
as the ``children's safety factor.''
IV. Carbofuran Background and Regulatory History
In July 2006, EPA completed a refined acute probabilistic dietary
risk assessment for carbofuran as part of the reassessment program
under section 408(q) of the FFDCA. The assessment was conducted using
Dietary Exposure Evaluation Model-Food Commodity Intake Database (DEEM-
FCID(TM), 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\1\ (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 above EPA's level of concern (Ref 15).
Since 2006, EPA has evaluated additional data submitted by the
registrant, FMC Corporation, and has further refined its original
assessment by incorporating more recent 2005/2006 PDP data, and by
conducting additional analyses. 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 Scientific Advisory Panel (SAP) on its
draft NOIC. Having considered the comments from the SAP, EPA is
initiating the process to revoke all carbofuran tolerances. As noted
above, aggregate exposures from food and water to the US population at
the upper percentiles of exposure substantially exceed the safe daily
levels and thus are ``unsafe'' within the meaning of FFDCA section
408(b)(2) (Ref 12). It is particularly significant that under every
analysis EPA has conducted, the levels of carbofuran exceed the safe
daily dose for children, even when EPA used the most refined data and
models available. Based on these findings, EPA has decided to move as
expeditiously as possible to address the unacceptable dietary risks to
children. EPA still expects to issue the NOIC subsequent to undertaking
the activities required to revoke the carbofuran tolerances.
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\1\ USDA's Pesticide Data Program monitors for pesticides in
certain foods at the distribution points just before release to
supermarkets and grocery stores.
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In May 2008, FMC Corporation, the sole U.S. registrant, submitted a
conditional request to cancel use of carbofuran on certain crops and to
add use restrictions intended to mitigate ground and surface water
contamination from use on other crops (Ref. 32). The tolerances that
would have been affected by that proposal are: alfalfa, fresh; alfalfa,
hay; artichoke, globe; barley, grain; barley, straw; sugar beet, tops;
cranberry; cucumber; grape; grape (raisin); oat, grain; oat, straw;
pepper; sorghum, fodder; sorghum, forage; sorghum, grain; strawberry;
soybean; soybean, forage; soybean, hay; squash; wheat, grain; wheat,
straw. FMC, however, conditioned the request on receiving assurance
from EPA that the Agency would permit the retention of several uses
that do not meet the FFDCA 408(b)(2) safety standard or the FIFRA
registration standard (Id.). EPA, therefore, could not accept the
request, and FMC has withdrawn it (Id.). The tolerances that FMC would
have sought to retain under that proposal were:
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banana, coffee bean; corn, forage; corn, fresh; corn, grain (including
popcorn); corn, stover; cotton, undelinted seed; melon; milk; potato;
rice, grain; rice, straw; sugarcane, cane; and sunflower, seed. Based
on the contribution from these foods alone, dietary exposures to
carbofuran would still be unsafe for the more sensitive children's
subpopulations. At the 99.9th percentile, carbofuran dietary exposure
from food alone was estimated at 0.000082 mg/kg/day (110% of the aPAD)
for children 3-5 years old, the population subgroup with the highest
estimated dietary exposure (Ref. 12). In addition, as discussed in more
detail in Refs 18 and 54, although FMC's proposed groundwater
restrictions would have protected against further contamination in the
most vulnerable locations, the Agency could not conclude that the
restrictions would be protective of all vulnerable groundwater. EPA
also has substantial questions about the efficacy of FMC's proposed
surface water restrictions to reduce drinking water exposure in
vulnerable reservoirs (Refs. 18 and 54). Accordingly, it has not been
shown that drinking water residues of carbofuran would no longer
contribute significantly to unsafe aggregate exposures, nor that such
exposures would meet the FFDCA safety standard.
V. 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
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., a 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 toxic 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 (for intraspecies extrapolation); 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 extrapolation.
Further, 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 factor. In implementing FFDCA section 408, EPA also
calculates a variant of the RfD referred to as a 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.
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 alone by multiple pathways of exposure. EPA uses available
data, together with assumptions designed to be protective of public
health and standard analytical methods, 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
probabilistic\2\ 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
[[Page 44868]]
environmental exposure of humans to carbofuran.
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\2\ 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. 58). 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. Data on the residues of carbofuran in foods
are available from a variety of sources. One of the primary sources of
the data comes from federally-conducted surveys, including the PDP
conducted by the USDA. Further, market basket studies, 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, EPA will rely on field trial data,
as it can provide more accurate exposure estimates (see below in Unit
VI.E.1).
EPA uses a computer program known as the DEEM-FCID to estimate
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.
DEEM-FCID contains consumption and demographic information on the
individuals who participated in the USDA's CSFII 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 program to estimate exposure and risk.
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 the
chosen value. 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
(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 is
actually a combination of two models: the Pesticide Root Zone Model
(PRZM) and the Exposure Analysis Model System (EXAMS).
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
[[Page 44869]]
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 takes
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 by the FIFRA SAP in 1999 and 1998, respectively (Refs. 25 and
26).
In modeling potential surface water concentrations, EPA attempts to
model areas of the country that are highly 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 believes these assessments are likely
reflective of a small subset of the watersheds across the country that
maintain drinking water reservoirs, representing a drinking water
source generally considered to be more vulnerable to frequent high
concentrations of pesticides than most locations that could be used for
crop production.
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.
C. Selection of Acute Dietary Exposure Level of Concern
Because probabilistic assessments generally present 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. 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
58).
VI. Aggregate Risk Assessment and Conclusions Regarding Safety
Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA's assessment of exposures and risks associated with
carbofuran use follows:
A. Toxicological Profile
Carbofuran is an N-methyl carbamate (NMC) pesticide. Like other
pesticides in this class, the primary toxic effect seen following
carbofuran exposure is neurotoxicity resulting from inhibition of the
enzyme acetylcholinesterase (AChE). AChE breaks down acetylcholine
(ACh), a compound that assists in transmitting signals through the
nervous system. Carbofuran inhibits the AChE activity in the body. When
AChE is inhibited at nerve endings, the inhibition prevents the ACh
from being degraded and results in prolonged stimulation of nerves and
muscles. Physical signs and symptoms of carbofuran poisoning include
headache, nausea, dizziness, blurred vision, excessive perspiration,
salivation, lacrimation (tearing), vomiting, diarrhea, aching muscles,
and a general feeling of severe malaise. Uncontrollable muscle
twitching and bradycardia (abnormally slow heart rate) can occur.
Severe poisoning can lead to convulsions, coma, pulmonary edema, muscle
paralysis, and death by asphyxiation. Carbofuran poisoning also may
cause various psychological, neurological and cognitive effects,
including confusion, anxiety, depression, irritability, mood swings,
difficulty concentrating, short-term memory loss, persistent fatigue,
and blurred vision (Refs. 15 and 16).
The most sensitive and appropriate effect associated with the use
of carbofuran is its toxicity following acute exposure. Acute exposure
is defined as an exposure of short duration, usually characterized as
lasting no longer than a day. EPA classifies carbofuran as Toxicity
Category I, the most toxic category, based on its potency by the oral
and inhalation exposure routes. The lethal potencies of chemicals are
usually described in terms of the ``dose'' given orally or the
``concentration'' in air that is estimated to cause the death of 50
percent of the animals exposed (abbreviated as LD50 or
LC50). Carbofuran has an oral LD50 of 7.8-6.0 mg/
kg, and an inhalation LC50 of 0.08 mg/l (Refs. 12, 16 and
48). The lethal dose and lethal concentration levels for the oral and
inhalation routes fall well below the limits for the Toxicity Category
I, < 50 mg/kg and < 0.2 mg/l, respectively (40 CFR 156.62).
Carbofuran has a steep dose-response curve. In other words, a
marginal increase in administered doses of carbofuran can result in a
significant change in the toxic effect. For example, carbofuran data in
juvenile rats (postnatal day 11 and 17) demonstrate that small
differences in carbofuran doses (0.1 mg/kg to 0.3 mg/kg) can change the
measured effect from significant brain and red blood cell (RBC) AChE
inhibition without clinical signs (0.1 mg/kg) to significant AChE
inhibition, and resultant tremors, and decreased motor activity (0.3
mg/kg) (Refs. 31 and 46). In other words there is a slight difference
in exposure levels that produce no noticeable outward effects and the
level that causes adverse effects. This means that small differences in
human exposure levels can have significant adverse consequences for
large numbers of individuals. For example, as discussed in greater
detail in Unit VI.E.1.b below, the difference between the amount of
food with carbofuran residues that can be safely consumed without
adverse effect, and the amount that provides a dose that exceeds safe
levels is minimal. Children who consume typical amounts of watermelon
(i.e., 8 grams) containing carbofuran residues of 0.009 ppm-a residue
level detected in PDP data--receive a safe daily dose, but those
consuming the same amount of watermelon with a PDP residue level of
0.013 receive an exposure of 130% of the safe daily dose.
[[Page 44870]]
B. Deriving Carbofuran's point of departure
EPA uses a weight of evidence approach to determine the toxic
effect that will serve as the appropriate PoD for a risk assessment for
AChE inhibiting pesticides, such as carbofuran (Ref. 61). The
neurotoxicity that carbofuran causes 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.). Although
RBC AChE inhibition is not adverse in itself, it is 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.). Due to technical
difficulties regarding dissection of peripheral nerves and the rapid
nature of carbofuran toxicity, measures of AChE inhibition in the PNS
are very rare for NMC pesticides. For these reasons, other state and
national agencies such as California, Washington, Canada, the European
Union, as well as the World Health Organization (WHO), all use blood
measures in human health risk assessment and/or worker safety
monitoring programs.
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. 16). 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 mentioned above do not occur.
EPA has relied on a benchmark dose approach for deriving the PoD
from the available rat toxicity studies. A benchmark dose, or 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 or typical value for the response of
concern. 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 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.
Numerous scientific peer review panels over the last decade have
supported the Agency's application of the BMD approach as a
scientifically supportable method for deriving PoDs in human health
risk assessment, and as an improvement over the historically applied
approach of using no-observed-adverse-effect levels (NOAELs) or lowest-
observed-adverse-effect-levels (LOAELs). The NOAEL/LOAEL approach does
not account for the variability and uncertainty in the experimental
results, which are due to characteristics of the study design, such as
dose selection, dose spacing, and sample size. With the BMD approach,
all the dose response data are used to derive a PoD. Moreover, the
response level used for setting regulatory limits can vary based on the
chemical and/or type of toxic effect (Refs. 27, 28, 29 and 57).
Specific to carbofuran and other NMCs, the FIFRA SAP has reviewed and
supported the statistical methods used by the Agency to derive BMDs and
BMDLs on two occasions, February 2005 and August 2005 (Refs. 28 and
29). Recently, in reviewing EPA's draft NOIC, the SAP again unanimously
concluded that the Agency's approach in using a benchmark dose to
derive the PoD from carbofuran brain AChE data in juvenile rats is
``state of the art science and the Panel strongly encouraged the Agency
to follow this approach for all studies where possible'' (Ref. 30).
There are laboratory data on carbofuran for cholinesterase activity
in plasma, RBC, and brain. EPA evaluated the quality of the AChE data
in all the available studies. In this review, particular attention was
paid to the methods used to assay AChE inhibition in the laboratory
conducting the study. Because of the nature of carbofuran inhibition of
AChE, care must be taken in the laboratory such that experimental
conditions do not promote enzyme reactivation (i.e., recovery) while
samples of blood and brain are being processed and analyzed. If this
reactivation occurs during the assay, the results of the experiment
will underestimate the toxic potential of carbofuran (Refs. 33, 37, 43,
66 and 67). Through its review of available studies, the Agency
identified problems and irregularities with the RBC AChE data from both
FMC supported studies. These problems are described in detail in the
Agency's study review (Refs. 19 and 20). As such, the Agency determined
that the RBC AChE inhibition data from both FMC studies were unreliable
and not useable in extrapolating human health risk. In addition, RBC
data from a study performed at EPA ORD did not provide doses low enough
to adequately characterize the full dose-response in postnatal day 11
(PND11) rats. In the recent SAP review of the draft carbofuran NOIC,
the Panel unanimously agreed with the Agency's conclusion, remarking
that ``[t]he Agency is well-justified in taking the position that the
data on AChE inhibition in rat RBC, particularly with regard to the
PND11 pups, are not acceptable for the purpose of predicting health
risk from carbofuran'' (Ref. 30). By contrast, the brain AChE data from
the FMC and EPA-ORD studies are acceptable and have been used in the
Agency's BMD analysis.
In EPA's BMD dose analysis to derive PoDs for carbofuran, the
Agency used a response level of 10% brain AChE inhibition and thus
calculated BMD10s and BMDL10s based on the
available carbofuran brain data. These values (the central estimate and
lower confidence bound, respectively) represent the estimated dose
where AChE is inhibited by 10% compared to untreated animals. In the
last few years EPA has used this 10% value to regulate AChE inhibiting
pesticides, including organophosphate pesticides and NMCs including
carbofuran. For a variety of toxicological and statistical reasons, EPA
chose 10%
[[Page 44871]]
brain AChE inhibition as the response level for use in BMD and BMDL
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 AChE level
(Refs. 28 and 29)
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 BMD10s, BMDL10s, and
half-life to recovery have been reviewed and supported by the FIFRA SAP
(Refs. 28 and 29). The meta-analysis approach offers the advantage over
using single studies by combining information across multiple studies
and thus provides a robust PoD.
There are three studies available which compare the effects of
carbofuran on PND11 rats with those in young adult rats (herein called
`comparative AChE studies') (Refs. 1, 2 and 46). 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.
45). 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 (Ref. 9). Other studies in adult rats used in the
Agency's analysis included additional data from EPA-ORD (Refs 44 and
46).
Using 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 (see Figure 1 in Unit VI.C. below). The Agency
believes the BMD analysis for the PND11 brain AChE data is the most
robust analysis for purposes of PoD selection.
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. 63). 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 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. As such, the focus of EPA's analysis of carbofuran's dietary
risk from residues in food and water is on young children (ages 0-5).
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.
Using data from PND11 pup brain AChE levels, the estimated oral
dose that will result in 10% brain AChE inhibition (BMD10)
is 0.04 mg/kg. The lower 95% confidence limit on the BMD10
(BMDL10) is 0.03 mg/kg--this BMDL10 of 0.03 mg/kg
provides the PoD.
As noted, although EPA does not consider RBC AChE inhibition as an
adverse effect in its own right, in the absence of data from peripheral
tissues, RBC AChE inhibition data are a critical component to
determining that a selected PoD will be sufficiently protective of PNS
effects. Because of the problems discussed previously with the
available RBC AChE inhibition data, there remains uncertainty
surrounding the dose-response relationship for RBC AChE inhibition in
pups, which the EPA-ORD data clearly show to be a more sensitive
endpoint than brain AChE. Consequently, EPA cannot reliably estimate
the BMD10 and BMDL10 for RBC AChE data in pups.
Furthermore, given that the EPA-ORD data clearly show RBC AChE to be
more sensitive than brain AChE, EPA cannot conclude that reliance on
the pup brain data as the PoD would be sufficiently protective of PNS
effects in pups. This uncertainty provides the scientific basis, in
part, for retention of the children's safety factor as described below.
C. Safety Factor for Infants and Children
1. In general. Section 408 of the FFDCA provides that EPA shall
apply an additional tenfold margin of safety for infants and children
in the case of threshold effects to account for prenatal and postnatal
toxicity and the completeness of the data base on toxicity and exposure
unless EPA determines that a different margin of safety will be safe
for infants and children. Margins of safety are incorporated into EPA
assessments either directly through use of a margin of exposure
analysis or through using uncertainty (safety) factors in calculating a
dose level that poses acceptable risk to humans.
In applying the children's safety factor provision, EPA has
interpreted the statutory language as imposing a presumption in favor
of applying an additional 10X safety factor (Ref. 60). Thus, EPA
generally refers to the additional 10X factor as a presumptive or
default 10X factor. EPA has also made clear, however, that the
presumption can be overcome if reliable data demonstrate that a
different factor is safe for children (Id.). 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 (Id.).
2. Prenatal and postnatal sensitivity. As noted in the previous
section, there are several studies in juvenile rats that show they 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 neurotoxicity (such as tremors) at lower doses in
the young rats. The SAP concurred with EPA that the data clearly
indicate that the juvenile rat is more sensitive than the adult rat
with regard to brain AChE (Ref. 30). However, the Agency does not have
AChE data for cabofuran in the peripheral tissue of adult or juvenile
animals; nor does the Agency have adequate RBC AChE inhibition data at
low doses relevant to risk assessment to serve as a surrogate in pups.
As previously noted the RBC AChE data from both FMC supported studies
are not reliable and thus are not appropriate for use in risk
assessment. Although the EPA studies did provide reliable RBC data,
they did not include data at the low end of the dose-response curve,
which is the area on the dose-response curve most relevant for risk
assessment (see Figure 1).
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There 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 (Ref. 64).
Based on this study, 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 (Refs. 11 and 30). These 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. It is important to note that these
clinical signs have been reported for at least one other cholinesterase
inhibiting pesticide at doses producing only blood, not brain, AChE
inhibition (Ref. 38). Thus, although RBC AChE inhibition is not an
adverse effect, per se, blood measures are used as surrogates in the
absence of peripheral tissue data. Assessment of potential for
neurotoxicity in peripheral tissues is a critical element of hazard
characterization for NMCs, like carbofuran. The lack of an appropriate
surrogate to assess the potential for RBC AChE inhibition is a key
uncertainty in the carbofuran toxicity database. Thus, EPA cannot
conclude that reliance on the pup brain data solely as the PoD will be
protective of PNS effects in pups.
To account for the lack of RBC 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
(and is considered an appropriate surrogate for the peripheral nervous
system), EPA is retaining a portion of the children's safety factor. On
the other hand, there are data available, albeit incomplete, which
characterize the toxicity of carbofuran in juvenile animals, and the
Agency believes 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.
This modified safety factor should take 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, as described above,
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 (Figure 1). As an alternative approach, EPA has 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. 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.
The Agency has recommended the application of a children's safety
factor of 4X, based on a weight-of-evidence approach. This safety
factor is calculated using the difference in RBC and brain AChE
inhibition, using the data on administered dose for the animals from
the EPA-ORD studies and the FMC studies combined. In other words, EPA
estimated the BMD50 for PND11 animals from each quality
study and used the ratio from the combined analysis, resulting in a
BMD50 ratio of 4.1X\3\. EPA also compared the
BMD50 ratios for PND17 pups (who are slightly less sensitive
than 11-day olds; see Figure 2) in the EPA-ORD study, resulting in a
BMD50 of 3.3 X. Conceptually, the RBC to brain potency ratio
could be estimated using two different approaches: 1) EPA's data for
RBC (the only reliable RBC data in PND11 animals for carbofuran) and
all available data in PND11 animals for brain; or 2) using only EPA's
data in PND11 animals for both RBC and brain. The former procedure, the
approach used by EPA, yields a ratio of about fourfold, while the
latter gives a twofold ratio for carbofuran. EPA has elected to use the
4X factor as the more health protective choice. This selection was made
based on: 1) uncertainty regarding lack of an appropriate measure of
peripheral toxicity (i.e., lack of RBC AChE inhibition data at the low
end of the dose response curve), and 2) the RBC to brain AChE ratio at
the BMD50 for PND17 animals of 3.3X which suggests that a
factor of 2X would not be protective of PND11 pups.
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\3\ EPA made a mathematical error when it originally calculated
the children's safety factor, which resulted in a factor of 5X (Ref.
50). Correcting the mathematical error results in a 4X actor.
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EPA recently presented its dietary risk assessment of carbofuran to
the FIFRA SAP, and requested comment on the Agency's approach to
selecting the point of departure and the children's safety factor.
Overall, the Agency believes that the Panel's responses support the
Agency's approach with regard to carbofuran's hazard identification and
hazard characterization. For example, the Agency notes that the Panel
``unanimously'' agreed with the Agency with regard to the conclusion
that the second FMC comparative cholinesterase (ChE) study provides
reliable brain, but not RBC, AChE data. The Panel further remarked
that, ``EPA is well-justified in taking the position that the data on
AChE inhibition in rat RBC, particularly with PND11 pups, are not
acceptable for the purpose of predicting health risk from carbofuran''
(Ref. 30). The Panel went on to concur with the Agency that the brain
AChE inhibition data from the FMC and EPA-ORD studies show ``good
concordance.'' With regard to the use of a benchmark dose approach to
derive a PoD from brain AChE data in pups, the Panel stated that the
Agency's approach is ``state-of-the-art science and the Panel strongly
encouraged the Agency to follow this approach for all studies where
possible'' (Id.).
The Panel provided five `scenarios' or options for applying the
children's safety factor and/or PoD. Four of the five scenarios
included the application of a children's safety factor. Because the
Panel report stated that the Panel was ``not in agreement regarding the
magnitude of a [children's] safety factor,'' it is reasonable to
conclude that a majority did not support any one of the five scenarios,
including the one advocating removal of the children's safety factor
(Ref. 30). It follows that a majority of the Panel agreed with the
Agency that at least a portion of the safety factor should be retained;
however, recommendations for the appropriate factor ranged between a 2X
and 10X. Two of the scenarios were consistent with the Agency's
approach in which the magnitude of the safety factor is derived based
on the differences in RBC and brain AChE responses, quantified by the
administered dose. The remaining two scenarios were based on retention
of the 10X safety factor. Those Panel members supporting retention of
the 10X safety factor did so on the basis that the statutory
requirement that EPA may use a different factor ```only if, on the
basis of reliable data, such margin will be safe for infants and
children.' Given the uncertainty in the data and in its interpretation
for risk assessment by the entire Panel, these Panel members believes
that this standard for change had not been met'' (Id.). 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. 23.
In sum, EPA has concluded that there is reliable data to support
the application of a 4X safety factor and has therefore applied this
safety factor in its dietary risk estimates. However, in light of the
disagreement among the SAP panelists on the appropriate factor to
apply, the Agency solicits comment on this issue.
D. Hazard Characterization and Point of Departure Conclusions
The doses and toxicological endpoints selected and Margins of
Exposures for various exposure scenarios are summarized in Table 1
below.
Table 1--Toxicology Endpoint Selection
----------------------------------------------------------------------------------------------------------------
FQPA factor and
Exposure Scenario Dose Used in Risk Endpoint for Risk Study and Toxicological
Assessment, UF Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary Infants and Children BMDL 10 = 0.03 mg/kg/ Children's SF = 4X Comparative AChE
day aPAD = 0.000075 mg/kg/ Studies in PND11 rats
UF = 100............... day. (FMC and EPA-ORD)
Acute RfD = 0.0003 mg/ BMD10 = 0.04 mg/kg/day
kg/day. BMDL10 = 0.03 mg/kg/
day, based on brain
AChE inhibition of
postnatal day 11
(PND11) pups
----------------------------------------------------------------------------------------------------------------
Acute Dietary Youth (13 and older) BMDL10 = 0.02 mg/kg/day Children's SF = 1X Comparative AChE Study
and Adults UF = 100............... aRfD = 0.0002 mg/kg/day (EPA-ORD), Padilla et
Acute RfD = 0.00024 mg/ al (2007), McDaniel et
kg/day. al (2007)
BMD10 = 0.06 mg/kg/day
BMDL10 = 0.02 mg/kg/
day, based on RBC AChE
inhibition in adult
rat
----------------------------------------------------------------------------------------------------------------
E. Dietary Exposure and Risk Assessment
1. Dietary exposure to carbofuran (food)--a. EPA methodology and
background. EPA conducted a refined (Tier 3) acute probabilistic
dietary risk assessment for carbofuran residues in food. Carbofuran is
registered for use on the following crops: alfalfa, artichokes, banana,
barley, corn, cranberry, cucumber, grapes, melons, milk, oats, peppers,
potatoes, pumpkin, rice, sorghum, soybean, spinach, squash, strawberry,
sugar beets, sugar cane, sunflower seed, and wheat. To conduct the
assessment, EPA relied on DEEM-FCID, Version 2.00-2.02, which uses food
consumption data from the USDA's CSFII from 1994-1996 and 1998.
Using data on the percent of the crop actually treated with
carbofuran and data on the level of residues that may be present on the
treated crop, EPA developed estimates of combined anticipated residues
of carbofuran and 3-hydroxycarbofuran on food. 3-Hydroxycarbofuran is a
degradate of carbofuran and is assumed to have toxic potency equivalent
to carbofuran (Refs. 12, 16 and 48). Anticipated residues of carbofuran
for most foods were derived using USDA PDP monitoring data from recent
years (through 2006 for all available commodities). In some cases,
where PDP data were not available for a particular crop, EPA translated
PDP monitoring data from surrogate crops based on the characteristics
of the crops and the use patterns. For example, PDP data for
cantaloupes were used to derive anticipated residues for casaba and
honeydew.
USDA PDP provides the most comprehensive sampling design, and the
most extensive and intensive sampling procedures for pesticide residues
of the various data sources available to EPA. Additionally, the intent
of PDP's sampling design is to provide statistically representative
samples of food commodities eaten by the U.S. population specifically
for the purpose of performing dietary risk assessments for pesticides.
The program focuses on high-consumption foods for
[[Page 44876]]
children and reflects foods typically available throughout the year. A
complete description of the PDP program (including all data through
2006) is available online.
The PDP analyzed for parent carbofuran and its metabolite of
concern, 3-hydroxycarbofuran. Most of the samples analyzed by the PDP
were measured using a high Level of Detection (LOD) and contained no
detectable residues of carbofuran or 3-hydroxycarbofuran. Consequently,
the acute assessment for food assumed a concentration equal to [frac12]
of the LOD for PDP monitoring samples with no detectable residues, and
0.00 ppm carbofuran to account for the percent of the crop not treated
with carbofuran.
An additional source of data on carbofuran residues was provided by
a market basket survey of NMC pesticides in single-serving samples of
fresh fruits and vegetables collected in 1999-2000 (Ref. 14), which was
sponsored by the Carbamate Market Basket Survey Task Force. EPA relied
on these data to construct the residue distribution files for 2 crops
(bananas and grapes) because the use of these data resulted in more
refined exposure estimates. The combined Limits of Quantitation (LOQs)
for carbofuran and its metabolite in the Market Basket Survey (MBS)
were between tenfold and twentyfold lower than the combined LODs in the
PDP monitoring data.
For certain crops where PDP data were not available (sugar beets,
sugarcane, and sunflower seed), anticipated residues were based on
field trial data. EPA also relied on field trial data for particular
food commodities that are blended during marketing (barley, field corn,
popcorn, oats, rice, soybeans and wheat), as use of PDP data can result
in significant overestimates of exposure when evaluating blended foods.
Field trial data are typically considered to overestimate the residues
that are likely to occur in food as actually consumed because they
reflect the maximum application rate and shortest preharvest interval
allowed by the label. However, for crops that are blended during
marketing, such as corn or wheat, use of field trial data can provide a
more refined estimate than PDP data, by allowing EPA to better account
for the percent of the crop actually treated with carbofuran.
EPA used average and maximum percent crop treated (PCT) estimates
for most crops, following the guidance provided in HED SOP 99.6
(Classification of Food Forms with Respect to level of Blending; 8/20/
99), and available processing and/or cooking factors. The maximum PCT
estimates were used to refine the acute dietary exposure estimates.
Maximum PCT ranged from <1 to 35%. The estimated percent of the crop
imported was applied to crops with tolerances currently maintained
solely for import purposes (cranberry, rice, strawberry).
b. Acute dietary exposure (food alone) results and conclusions. The
estimated acute dietary exposure from carbofuran residues in food alone
(i.e., assuming no additional carbofuran exposure from drinking water),
exceeds EPA's level of concern for all but one of the children's
population subgroups at the 99.9th percentile of exposure. Carbofuran
dietary exposure at the 99.9th percentile was estimated at 0.000156 mg/
kg/day (210% of the aPAD) for children 3-5 years old, the population
subgroup with the highest estimated dietary exposure. Estimated dietary
exposure to carbofuran also exceeds EPA's level of concern for children
1-2 years old and 6-12 years at the 99.9th percentile of exposure. (See
results Table 2 below).
Table 2--Results of Acute Dietary Exposure Analysis for Food Alone
----------------------------------------------------------------------------------------------------------------
99th Percentile 99.9th Percentile
aPAD (mg/kg/---------------------------------------------------
Population Subgroup day) Exposure Exposure
(mg/kg/day) % aPAD (mg/kg/day) % aPAD
----------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.000075 0.000025 33 0.000070 93
----------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.000075 0.000045 60 0.000152 200
----------------------------------------------------------------------------------------------------------------
Children 3-5 years old 0.000075 0.000036 48 0.000156 210
----------------------------------------------------------------------------------------------------------------
Children 6-12 years old 0.000075 0.000024 32 0.000121 160
----------------------------------------------------------------------------------------------------------------
Exposure estimates for all of the major food contributors were
based on PDP monitoring data adjusted to account for the percent of the
crop treated with carbofuran and, therefore, may be considered highly
refined.
As noted previously, because most of the PDP samples contained no
detectable residues of carbofuran or its 3-hydroxy metabolite, the
acute assessment for food assumed a concentration equal to [frac12] of
the LOD for PDP monitoring samples with no detectable residues, with
0.00 ppm carbofuran incorporated to account for the percent of the crop
not treated with carbofuran. In accordance with OPP policy for
analyzing commodities with non-detectable residues, EPA performed
additional analyses to determine the impact of using [frac12] the LOD
to estimate exposure (Ref. 56).
In the first analysis (Sensitivity Analysis 1), those
commodities that had no detectable residues at all in either the
monitoring data or field trials were eliminated from the assessment.
The commodities that were eliminated included barley, coffee, corn,
cranberry, oats, potato, raisin, rice, soybean, spinach, strawberry,
sugar beet, sunflower, winter squash, and wheat. For the remaining
commodities, on which carbofuran was detected, EPA continued to
substitute the [frac12] LOD values for the percent of the crop treated
with carbofuran, with 0.00 ppm carbofuran incorporated to account for
the remaining untreated percent of the crop. This analysis resulted in
estimated exposures that were still above EPA's level of concern for
children 1-2 at the 99.9th percentile (115% of the aPAD; see Table 3
below).
To further understand the extent to which the [frac12] LODs from
the PDP monitoring data were affecting the risk assessment, EPA
conducted an additional sensitivity analysis, (Sensitivity Analysis
2) that excluded the crops for which PDP and MBS data were not
available and assigned 0.00 ppm carbofuran for all non-detected
residues in commodities sampled in the PDP or MBS. In other words, an
analysis using only detectable residues from residue monitoring
programs was conducted. In this analysis, estimated dietary exposures
at the 99.9th percentile of exposure remained above EPA's level of
concern for children 1-2 yrs. old (114% of the aPAD). The
[[Page 44877]]
results of these sensitivity analyses at the 99.9th percentile of
exposure are compared to the results using [frac12] LOD for non-
detectable residues in Table 3 below.
Table 3--Impact of Using [frac1s2] LOD for Non-Detectable Residues on Estimated Exposure From Food\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Analysis Assuming Sensitivity Analysis Sensitivity Analysis
[frac1s2] LOD for Non- 1\2\ 2\3\
aPAD (mg/kg/ Detectable Residues -----------------------------------------------
Population Subgroup day) ------------------------
Exposure Exposure % aPAD Exposure % aPAD
(mg/kg/day) % aPAD (mg/kg/day) (mg/kg/day)
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.000075 0.000070 93 0.000044 58 0.000043 57
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.000075 0.000152 200 0.000086 115 0.000086 114
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old 0.000075 0.000156 210 0.000066 88 0.000065 87
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old 0.000075 0.000121 160 0.000039 52 0.000038 51
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ At the 99.9th Percentile of Exposure.
\2\ Non-detectable PDP residues assumed to be zero only for commodities having no detectable residues at all in the PDP monitoring data and field trials
(i.e., these commodities were eliminated from the analysis). Crops without PDP data and detectable residues in field trials were included, based on
the distribution of residues from field trial studies.
\3\ Non-detectable residues assumed to be zero for all commodities. Commodities without PDP or Market Basket data were excluded from the analysis.
The major contributors in Sensitivity Analysis 2, to the
estimated dietary exposure of children are listed in Table 4 below.
Table 4--Major Contributors to Carbofuran Acute Exposure at the 99.9th
Percentile in Sensitivity Analysis 2 (Expressed as an
Approximate Percent of Total Exposure)
------------------------------------------------------------------------
Children, 1- Children, 3-
Food Infants, <1 2 Years Old 5 Years Old
year old
------------------------------------------------------------------------
Cantaloupe 9 18 20
------------------------------------------------------------------------
Squash 10 2 1
------------------------------------------------------------------------
Grape 15 10 5
------------------------------------------------------------------------
Cucumbers 2 20 29
------------------------------------------------------------------------
Milk 32 <1 1
------------------------------------------------------------------------
Watermelon 29 39 41
------------------------------------------------------------------------
EPA's evaluation of these two sensitivity analyses and other
information on carbofuran residue levels yields three conclusions.
First, the results of the sensitivity analyses indicate that the
dietary risk assessment for carbofuran is sensitive to the assumed
concentrations (i.e., [frac12] LOD) for non-detectable residues in the
PDP monitoring data. This sensitivity appears to be more of a factor
for commodities with no detections because the main difference between
the Sensitivity Analyses 1 and 2 was substituting
0.00 ppm for [frac12] LODs for commodities with detects in the second
analysis yet that analysis yielded similar results to the first
sensitivity analysis. On the other hand, both sensitivity analyses were
approximately 2X lower than the analysis that used [frac12] LOD for all
treated commodities. The finding that the use of a [frac12] LOD
assumption had a noticeable impact on the risk estimate is contrary to
EPA's experience in conducting pesticide risk assessments. Generally,
risk estimates do not show noticeable differences whether non-detects
are treated as true zeros or [frac12] LODs. In all likelihood, this is
a factor of the relatively insensitive level of the carbofuran method's
LOD.
Second, given that there are data showing that carbofuran is found
at levels below the LOD when a more sensitive method was used, EPA
finds that use of either of the approaches in the sensitivity analyses
will understate carbofuran risk. The available information demonstrates
that carbofuran residues are present; when a lower level of detection
was utilized, both in the most recent PDP milk analyses and in the
Carbamate MBS data; residues of carbofuran and 3-hydroxycarbofuran were
detected in commodities that previously had no detections. Moreover,
detected residues ranged between levels below and above [frac12] LOD.
Thus, unlike the circumstance where a relatively sensitive method of
detection is used and there is some uncertainty as to whether a non-
detect may mask an actual exposure, with cabofuran there is no question
- treating all non-detects as zero clearly would mask actual exposures
to carbofuran. Thus, these sensitivity analyses do not provide a basis
for concluding that EPA has overestimated risk.
Third, and most important, EPA would call attention to the fact
that these sensitivity analyses, although clearly underestimating
actual carbofuran exposure and risk, still indicate that one group of
children will have exposures exceeding the safe level.
Because it appears that carbofuran's dietary risks to children are
driven by
[[Page 44878]]
relatively low residues in a small percentage of commodities, and to
try to gain further insight into the potential impact of using [frac12]
LOD in this case, EPA conducted a third sensitivity analysis to
evaluate whether its estimates that food only and aggregate carbofuran
exposure results in risks of concern were overstated. EPA combined
actual residue values measured in the food supply (from PDP and MBS
data) with the typical (50th percentile) and high-end (90th percentile)
amounts of a single commodity that a child would be expected to
consume, and compared that to the aPAD, without considering the
likelihood that a child would be exposed to that residue value. The
results one of these analyses are summarized in Table 5 below.
Table 5--Risk to Children Consuming Typical or High-End Amounts of Fresh (Uncooked) Cucumbers Containing Carbofuran Residues
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Typical: 50th Percentile of Consumption High-End: 90th Percentile of Consumption
------------------------------------------------------------------------------------------------------------------------
Food Population Subgroup PDP Exposure PDP Exposure
Consumption (g/kg bw) Residue\1\ (mg/kg % aPAD Consumption (g/ Residue\1\ (mg/kg % aPAD
(ppm) bw) kg bw) (ppm) bw)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Cucumbers (Uncooked) DEEM food form 110 Children 1-2 1.0 0.005 0.000005 7 4.3 0.005 0.000022 29
-------------------------------------- ------------------------------------
0.029 0.000029 39 0.029 0.000125 170
-------------------------------------- ------------------------------------
0.063 0.000063 84 0.063 0.000271 360
-------------------------------------- ------------------------------------
0.117 0.000117 160 0.117 0.000503 670
-------------------------------------- ------------------------------------
0.137 0.000137 180 0.137 0.000589 790
-------------------------------------- ------------------------------------
0.147 0.000147 200 0.147 0.000632 840
-------------------------------------- ------------------------------------
0.437 0.000437 580 0.437 0.001879 2,500
-------------------------------------- ------------------------------------
0.537 0.000537 720 0.537 0.002309 3,100
======================================================================================================================================================
Children 3-5 0.8 0.005 0.000004 5 5.1 0.005 0.000026 34
-------------------------------------- ------------------------------------
0.029 0.000023 31 0.029 0.000148 200
-------------------------------------- ------------------------------------
0.063 0.000050 67 0.063 0.000321 430
-------------------------------------- ------------------------------------
0.117 0.000094 120 0.117 0.000597 800
-------------------------------------- ------------------------------------
0.137 0.000110 150 0.137 0.000699 930
-------------------------------------- ------------------------------------
0.147 0.000118 160 0.147 0.000750 1,000
-------------------------------------- ------------------------------------
0.437 0.000350 470 0.437 0.002229 3,000
-------------------------------------- ------------------------------------
0.537 0.000430 570 0.537 0.002739 3,700
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ The PDP detected residues of carbofuran in 11 of 1479 cucumber samples at levels ranging from 0.005 ppm to 0.537 ppm.
Detectable residues of carbofuran and/or 3-hydroxycarbofuran were
found in only a few samples of cucumber in monitoring data (11 out of
1479 or less than one percent). However, if young children aged 1 to 5
consume moderate amounts of cucumber (i.e., the median or 50th
percentile of consumption, corresponding to approximately 1 gram per kg
of body weight of cucumber) that contain actual levels of carbofuran
measured in the food supply, the percent of the aPAD that would be
utilized ranges from about 7% of the safe daily dose for the lower
observed residue values to 720% of the safe daily dose for the higher
observed values. For children who consume larger amounts of cucumber
(i.e., the 90th percentile of consumption, corresponding to 5 grams per
kg of body weight of cucumber or roughly [frac12] cup), exposure
increases approximately tenfold (29% to over 3700% of the aPAD). Many
of these values significantly exceed the Agency's level of concern
based on the consumption of a single daily serving of one commodity.
Additional analyses are summarized in Table 6 below, and analyses
on additional foods can be found in Ref. 12. EPA focused on children in
making these calculations, because children have the highest estimated
dietary exposure to carbofuran; however, it is reasonable to assume
that adult exposures from a single treated food item could also exceed
EPA's level of concern, particularly at the high end of consumption.
[[Page 44879]]
Table 6--Risk to Children Consuming Typical or High-End Amounts of Cantaloupe or Watermelon Containing Carbofuran Residues
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Typical: 50th Percentile of Consumption High-End: 90th Percentile of Consumption
------------------------------------------------------------------------------------------------------------------------------------------------
Population Subgroup PDP Residue Exposure Consumption (g/kg Exposure
Consumption (g/kg bw) (ppm) (mg/kg bw) % aPAD bw) PDP Residue (ppm) (mg/kg bw) % aPAD
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Cantaloupe
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 Approx. 6g 0.009 0.0000531 71 Approx. 12 g 0.009 0.0001035 140
---------------------------------------- --------------------------------------------------
0.01 0.000059 79 0.01 0.000115 150
---------------------------------------- --------------------------------------------------
0.02 0.000118 160 0.02 0.00023 310
---------------------------------------- --------------------------------------------------
0.06 0.000354 470 0.06 0.00069 920
---------------------------------------- --------------------------------------------------
0.085 0.0005015 670 0.085 0.0009775 1,300
---------------------------------------- --------------------------------------------------
0.357 0.0021063 2,800 0.357 0.0041055 5,500
================================================================================================================================================================================================
Children 3-5 approx. 5g 0.009 0.0000441 59 approx. 15g or 0.009 0.0001368 180
[frac1s2] cup
---------------------------------------- --------------------------------------------------
0.01 0.000049 65 0.01 0.000152 200
---------------------------------------- --------------------------------------------------
0.02 0.000098 130 0.02 0.000304 400
---------------------------------------- --------------------------------------------------
0.06 0.000294 390 0.06 0.000912 1,200
---------------------------------------- --------------------------------------------------
0.085 0.0004165 560 0.085 0.001292 1,700
---------------------------------------- --------------------------------------------------
0.357 0.0017493 2,300 0.357 0.0054264 7,200
================================================================================================================================================================================================
Watermelon
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 approx. 8g 0.0057 0.00004332 58 less than 30g 0.0057 0.00014706 200
---------------------------------------- --------------------------------------------------
0.009 0.0000684 91 0.009 0.0002322 310
---------------------------------------- --------------------------------------------------
0.0132 0.00010032 130 0.0132 0.00034056 450
---------------------------------------- --------------------------------------------------
0.014 0.0001064 140 0.014 0.0003612 480
---------------------------------------- --------------------------------------------------
0.062 0.0004712 630 0.062 0.0015996 2,100
---------------------------------------- --------------------------------------------------
0.081 0.0006156 820 0.081 0.0020898 2,800
---------------------------------------- --------------------------------------------------
0.205 0.001558 2,100 0.205 0.005289 7,100
================================================================================================================================================================================================
Children 3-5 approx. 12g 0.0057 0.00007125 95 approx. 35g 0.0057 0.00019893 270
---------------------------------------- --------------------------------------------------
0.009 0.0001125 150 0.009 0.0003141 420
---------------------------------------- --------------------------------------------------
0.0132 0.000165 220 0.0132 0.00046068 610
---------------------------------------- --------------------------------------------------
0.014 0.000175 230 0.014 0.0004886 650
---------------------------------------- --------------------------------------------------
0.062 0.000775 1,000 0.062 0.0021638 2,900
---------------------------------------- --------------------------------------------------
0.081 0.0010125 1,400 0.081 0.0028269 3,800
---------------------------------------- --------------------------------------------------
0.205 0.0025625 3,400 0.205 0.0071545 9,500
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 44880]]
The analyses in Tables 5 and 6 demonstrate three significant
points. First, the fact that individual children, consuming typical
amounts of a single food item receive unsafe levels of carbofuran,
based on actual residue levels measured in the food supply, strongly
supports EPA's findings that aggregate exposures to carbofuran are
unsafe. It is true that the results described in Tables 5 and 6, as
well as the additional analyses in Ref. 12, do not describe the
probability that an individual child will receive those residues on the
foods they consume. By contrast, EPA's analyses in Tables 2 and 3
account for the probability that a particular level of residues will be
present on a food item, as well as the likelihood that an individual
will consume a particular food. It is EPA's typical approach, as was
done with carbofuran, to conduct its estimates of exposure across the
entire population, generally assuming that as long as the 99.9th
percentile of the estimated daily exposure is equal to or less than the
aPAD, there is a reasonable certainty of no harm to the general
population, including all significant subpopulations (Ref. 58). In
practice, this can mean that if only a small portion of the population
reported eating the commodity, or if the residues are infrequently
detected, individual high-end risks may fall above EPA's usual
benchmark of the 99.9th percentile, or in other words, fall in the
``tail end'' of the distribution curve. Admittedly, some of the results
described in Tables 5 and 6 would be expected to fall within this tail
end, given the relatively infrequent detections of carbofuran in
sampled commodities. However, taking into account the analysis of the
risk drivers in Table 4 above, it is clear that some of these values do
fall within the 99.9th percentile.
In any event, given all of the facts, it is just as appropriate for
EPA to evaluate whether the eating occasions that drive a conclusion
that risks at the 99.9th percentile yield unacceptable risks are
realistic, as it is for EPA to examine whether eating occasions in the
tail of a distribution curve are examples of consumption events the
Agency should be concerned about. In this regard, it is notable that
even the high-end consumption values described in Tables 5 and 6 are
extremely likely to be valid reported consumption events--or in other
words, consumption of the amounts at the 90th percentile are quite
realistic. For example, a child between 3-5 years, who consumes a
[frac12] cup of cantaloupe would receive a dose ranging between 180%
and 7,200% of the aPAD. Accordingly, this analysis by itself supports a
conclusion that the carbofuran tolerances are not safe and certainly
buttresses EPA's conclusions that exposures from carbofuran in food or
water alone or from carbofuran residues in food and water aggregated
when assessed at the 99.9th percentile are not safe.
Additionally, because of the uncertainty surrounding carbofuran's
exposure potential, investigation of individual children's risks, even
if in the ``tail end,'' is particularly relevant. There are a number of
reasons that significant uncertainty remains with respect to
carbofuran's exposure potential. One primary consideration stems from
the high LOD for carbofuran and consequent large numbers of non-detects
in the PDP data. The LOD for most commodities is tenfold to twentyfold
higher than the more precise methods used for the CMS and some of the
more recent PDP data. Generally, EPA would consider use of [frac12] LOD
as a conservative way of addressing non-detects but that may not be the
case where the LOD is relatively insensitive and the risk of concern is
an acute exposure. For acute risks, the higher values in a
probabilistic risk assessment are often driven by relatively high
values in a few commodities rather than relatively lower values in a
greater number of commodities. 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 foods consumed. Thus, to the extent
that there is a high exposure it will be more likely due to a high
residue value in a single commodity. However, assuming [frac12] LOD for
non-detects does not reflect that the non-detects actually will bear a
range of values from close to or near zero to close to or near the LOD.
Importantly, those commodities bearing residues only slightly below the
LOD may result in an exceedance of the aPAD where assuming [frac12] LOD
would not. In this way, the [frac12] LOD analysis may actually
understate risk. In these circumstances, reliance on [frac12] LOD can
skew the distribution of residues, which in turn masks the true ``tail
end'' of exposures. In other words, to the extent that the [frac12] LOD
underestimates exposures for some individual commodities, it
effectively decreases the probability of receiving higher residues,
thereby shifting those values with greater risks to the tail end of the
distribution curve, above the 99.9th percentile.
The second important point from these tables is that the
exceedances from both the 50th and 90th percentile consumer are quite
large--sometimes orders of magnitude above safe doses. The size of
these exceedances gives rise to concerns that the exceedances are more
likely to result in actual harm to exposed individuals, particularly if
they are also consuming carbofuran-contaminated drinking water.
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.
Finally, that Tables 5 and 6 show large exceedances across several
crops for which relatively more residue data are available suggests
these results are not unique to the specific crops for which precise
residues have been detected in PDP and MBS. In other words, crops for
which such residue data are not available may be posing similar risks.
In sum, these results strongly support EPA's conclusion that its
dietary exposure assessment for carbofuran has not overstated exposure
and risk. Further, serious questions remain as to the extent to which
similar exceedances exist for all crops, but which remain undetected,
because, as result of the high LOD, EPA lacks precise residue levels
for the majority of crops.
2. Drinking water exposures. EPA's drinking water assessment uses
both monitoring data for carbofuran and modeling methods, and takes
into account contributions from both surface water and groundwater
sources (Refs. 3, 4, 13, 36 and 47). Concentrations of carbofuran in
drinking water, as with any pesticide, are in large part determined by
the amount, method, timing and location of pesticide application, the
chemical properties of the pesticide, the physical characteristics of
the watersheds and/or aquifers in which the community water supplies or
private wells are located, and other environmental factors, such as
rainfall, which can cause the pesticide to move from the location where
it was applied. While there is a considerable body of monitoring data
that has measured carbofuran residues in surface and groundwater
sources, 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). Because pesticide loads in surface
water tend to move in relatively quick pulses in
[[Page 44881]]
flowing water, frequent targeted sampling is necessary to reliably
capture peak concentrations for surface water sources of drinking
water. Pesticide concentrations in ground water, however, are generally
the result of longer-term processes and less frequent sampling can
better 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 for both surface and
groundwater tends to underestimate exposure for acute endpoints.
Simulation modeling complements monitoring by making estimations at
vulnerable sites and can be used to represent daily concentration
profiles, based on a distribution of weather conditions. Thus, modeling
can account for the cases when a pesticide is used in drinking water
watersheds at any rate and is applied to a substantial proportion of
the crop. It can also account for stochastic processes, such as
rainfall represented by 30 years of existing weather data maintained by
the National Oceanic and Atmospheric Administration.
a. Exposure to carbofuran from drinking water derived from ground
water sources. Drinking water taken from shallow wells is particularly
vulnerable to contamination in areas where carbofuran is used around
sandy, highly acidic soil. Some areas with these characteristics
include Long Island, parts of Florida, and the Atlantic coastal plain,
in addition to other areas of the country. Exposure estimates for this
assessment are drawn primarily from (1) the results of a prospective
groundwater (PGW) study developed by the registrant in the early 1980s;
and (2) additional groundwater modeling conducted as part of the NMC
cumulative assessment in 2007. The results of the PGW study are
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 (Refs. 13 and 47). For example, a study
in Manitoba, Canada assessed the movement of carbofuran into tile
drains and groundwater 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 groundwater samples ranged between 0
(non-detect) and 158 ppb, with a mean of 40 ppb (Refs. 13 and 47).
While there have been additional groundwater 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. Accordingly, EPA believes the PGW study
continues to be the most relevant monitoring data for assessing
drinking water exposures from private wells at vulnerable sites.
Because this study was conducted over only one growing season, however,
and was conducted at use rates that now exceed current label maximum
rates for the use being studied (3 lb ai/acre vs. the current 2 lb ai/
acre for corn), EPA has scaled the results to represent impacts from
carbofuran use over a long-term period (25 years) at current label
rates. Temporal scaling was necessary because the PGW study represents
water quality impacts from a single application rather than repeated
years of use. Based on EPA's assessment, the maximum 90-day average
carbofuran concentrations in vulnerable groundwater for various
application rates were estimated to range from a low of 11 parts per
billion (ppb) based on a 1 pound per acre application rate, to a high
of 34 ppb, based on a 3 pound per acre application rate. The peak
concentration measured in the PGW study was 65 ppb. Because the
degradate 3-hydroxycarbofuran, which is assumed to be of equal potency
with the parent compound, was not measured in this study, exposure was
not estimated. Although the failure to include the degradate is
expected to underestimate exposure to some degree, the extent to which
it would contribute to exposure is unclear.
EPA conducted additional groundwater modeling for the NMC
cumulative risk assessment, and developed a time series of exposures at
locations selected based on potential for exposure to a combination of
carbamate insecticides relevant for cumulative exposure assessment for
use in probabilistic dietary assessments using DEEM. EPA estimated
carbofuran groundwater concentrations associated with two possible use
scenarios: potatoes in northeastern Florida and cucurbits on the
Delmarva Peninsula in the Mid-Atlantic region. While the modeled potato
use scenario in Florida did not show concentrations of carbofuran of
concern, estimated carbofuran concentrations associated with the
cucurbit use in the Delmarva Peninsula - a region with shallow, acidic
groundwater and acidic, sandy soils - are consistent with EPA's
assessment of the PGW study discussed above. Specifically, the
assessment indicated that at an application rate of 1.25 pounds a.i.
per acre, on cucurbits, maximum concentrations were 38.5 ppb (Ref. 63).
EPA does not believe the results of this assessment are particularly
conservative, since the application rate used in this assessment was
less than the maximum rate of 1.94 lb/acre that growers can use. Also,
concentrations of the degradate, 3-hydroxycarbofuran were not included
in modeling simulations, which would tend to underestimate exposure to
some degree.
Based on these estimates, EPA compiled a distribution of estimated
carbofuran concentrations in water that could be used to generate
probabilistic assessments of the potential exposures from drinking
water derived from vulnerable ground water sources. The results of
EPA's probabilistic assessments are represented below in Table 7. As
discussed in the previous section, it is important to remember that the
aPAD for carbofuran is quite low, hence, relatively low concentrations
of carbofuran monitored or estimated in vulnerable groundwater can have
a significant impact on the aPAD utilized.
Table 7--Results of Acute Dietary (Ground Water Only) Exposure Analysis Using DEEM FCID and Incorporating the Delmarva Ground Water Scenario
(Representing Private Wells)
--------------------------------------------------------------------------------------------------------------------------------------------------------
95th Percentile 99th Percentile 99.9th Percentile
aPAD (mg/kg/-----------------------------------------------------------------------
Population Subgroup day) Exposure Exposure Exposure
(mg/kg/day) % aPAD (mg/kg/day) % aPAD (mg/kg/day) % aPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.000075 0.003800 5,100 0.006006 8,000 0.010030 >10,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.000075 0.001612 2,100 0.002732 3,600 0.004628 6,200
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 44882]]
Children 3-5 years old 0.000075 0.001459 1,900 0.002405 3,200 0.004613 5,600
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old 0.000075 0.001018 1,360 0.001710 2,300 0.002792 3,700
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old 0.0002 0.000809 400 0.001441 720 0.002919 1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old 0.0002 0.000955 480 0.001632 820 0.003073 1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old 0.0002 0.000884 440 0.001345 670 0.002271 1,100
--------------------------------------------------------------------------------------------------------------------------------------------------------
While the registrant has attempted to address drinking water
exposure from ground water sources by including on current carbofuran
product labeling an advisory statement warning growers against
application in vulnerable areas, this language does not prohibit use in
such areas. In addition, EPA does not believe that the available
information demonstrates that even the additional restrictions that FMC
included on its labels submitted in May, 2008 would adequately mitigate
the risk of contaminating all vulnerable ground water (Refs. 18 and
54). For example, those restrictions were based on the use of a
particular methodology to evaluate the characteristics in the site used
in the PGW study in the Delmarva Penninsula. Using that as a surrogate
to identify sites with vulnerability to ground water contamination, FMC
identified counties that had higher vulnerability scores than the site
used for the PGW study in the Delmarva Penninsula, and proposed label
restrictions to preclude use in such areas. While EPA agrees in
principle that precluding use in sites vulnerable to leaching can
mitigate the risks, and even presuming that the methodology used by FMC
adequately identifies those sites, sites less vulnerable than the PGW
site would still be vulnerable to contamination, and the proposed
restrictions in no way addressed the less sensitive, but still
vulnerable, sites (Refs. 18 and 54). Accordingly, EPA continues to
believe that its assessment of drinking water from groundwater sources
based on current labels is a realistic assessment of potential
exposures to those portions of the population consuming drinking water
from shallow wells in highly vulnerable areas.
b. Exposure from drinking water derived from surface water sources.
EPA's evaluation of environmental drinking water concentrations of
carbofuran from surface water, as with its evaluation of groundwater,
takes into account the results of both surface water monitoring and
modeling.
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 groundwater wells,
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 process are
less effective in removing carbofuran (Ref. 63). 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 121% of the aPAD. 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 210% of the aPAD.
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 United States Geological Survey
National Water Quality Assessment (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. A
detailed description of the pesticide monitoring component of the NAWQA
program is available on the NAWQA Pesticide National Synthesis Project
(PNSP) web site (http://ca.water.usgs.gov/pnsp/).
A summary of the first cycle of NAWQA monitoring from 1991 to 2001
indicates that carbofuran was the most frequently detected carbamate
pesticide in streams and ground water in agricultural areas. Overall,
where
[[Page 44883]]
carbofuran was detected, these non-targeted monitoring results
generally found carbofuran at levels below 0.5 ppb. In the NMC
assessment, EPA summarized NAWQA monitoring for carbofuran between 1991
and 2004. Maximum surface-water concentrations exceeded 1 ppb in
approximately nine agricultural watershed-based study units, with
detections in the sub-ppb range reported in additional watersheds (Ref.
63). The highest concentrations of carbofuran are reported from at a
sampling station on Zollner Creek, in Oregon. Zollner Creek, located in
the Molalla-Pudding sub-basin of the Willamette River, is not directly
used as a drinking water source. This creek is a low-order stream and
its watershed is small (approximately 40 km2) and intensively farmed,
with a diversity of crops grown, including plant nurseries. USGS
monitoring at that location from 1993 to 2006 detected carbofuran
annually in 40-100 % of samples. Although the majority of
concentrations detected there are also in the sub-part per billion
range, concentrations have exceeded 1 ppb in 8 of the 14 years of
sampling. The maximum measured concentration was 32.2 ppb, observed in
the spring of 2002. The frequency of detections generally over a 14-
year period suggests that standard use practices rather than
aberrational misuse incidents in the region are responsible for high
concentration levels at this location.
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. 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 (concentrations of 4-7 ppb would result in exposures of 121-210% of
the aPAD for an infant consuming 8 oz of water) and levels of
approximately 1 to 30 ppb measured in streams representative of those
in watersheds that support drinking water systems (Ref. 63). 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 the risks
posed by carbofuran in surface drinking water are below thresholds of
concern. Nor can this data be reasonably used to establish a lower
bound of potential carbofuran risk through this route of exposure.
To further characterize carbofuran risk through drinking water
derived from surface water sources, EPA modeled estimated daily
drinking water concentrations of carbofuran using PRZM to simulate
field runoff processes and EXAMS to simulate receiving water body
processes. These models were summarized in Unit V.B.2.
There are sources of uncertainty associated with estimating
exposure of carbofuran in surface water source drinking water. Several
of the most significant of these are the effect of treatment in
removing carbofuran from finished drinking water before it is delivered
to the consumer supply system, the impact of percent crop treated
assumptions, and the variation in pH across the landscape. The effect
of the percent crop treated assumption in the case of carbofuran is
discussed in detail in EPA's assessment of additional data submitted by
the registrant (Refs. 18 and 54) and summarized below. Available data
on the degree to which carbofuran may be removed from treatment systems
was summarized previously and is discussed in more detail in Appendix
E-3 of the Revised NMC Cumulative Assessment (Ref. 63). Although EPA is
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 are difficult to incorporate quantitatively in
drinking water exposure estimates. Therefore, EPA assumes that there is
no reduction in carbofuran concentrations in surface water source
drinking water due to treatment, which is a source of conservatism in
surface water exposure estimates used for human health risk assessment.
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 a neutral pH (pH 7) default
value was used to estimate water concentrations. Finally, available
environmental fate studies do not show formation of 3-hydroxycarbofuran
through most environmental processes except soil photolysis, where in
one study it was detected in very low amounts. Although 3-
hydroxycarbofuran was not explicitly considered as a separate entity in
the drinking water exposure assessment, it is unclear whether it would
significantly add to exposure estimates.
EPA compiled a distribution of estimated carbofuran concentrations
in surface water in order to conduct probabilistic assessments of the
potential exposures from drinking water. For the IRED, EPA modeled
crops representing 80 percent of total carbofuran use at locations that
would be considered among the more vulnerable where the crops are
grown. Modeling was conducted at a range of application rates and
included adjustments to reflect different regional levels for
agricultural intensity, resulting in estimated 1-in-10-year (peak)
concentrations of 0.11-75 ppb (Refs. 5 and 36). For corn, carbofuran
concentration estimates assuming different rates and regional percent
cropped area (PCA) factors reflective of corn intensity nationally
resulted in a range of peak concentrations of 4 - 26 ppb. For the
dietary risk assessment, EPA generated distributions for 13 different
scenarios representing all labeled uses of carbofuran treated at
maximum label rates and adjusted with PCA factors (Refs. 3, 13 and 47).
Peak concentrations for these distributions ranged from 3.2 to 168 ppb
(excluding use on bananas), with the corn use at 26 ppb (Refs. 3 and
47).
EPA has subsequently conducted several rounds of modeling to refine
estimates for specific uses and agricultural practices. One set of
refinements addressed use of carbofuran on corn at typical rather than
maximum label rates and application practices that assume the only use
of carbofuran in a watershed is on corn. Simulations included those
specific to control European corn borer, a rescue treatment for corn
rootworm, and an in-furrow application at plant. The assessment also
included estimates resulting from treatment at the maximum label rate,
for comparative purposes. The peak concentrations estimated ranged from
3.9 to 16.6 ppb for the refined analyses, compared to 32.9 ppb at the
maximum application rate (Ref. 4). The range of 3.9 to 16.6 ppb is
approximately 1 to 4 times the values of the 4 ppb detected in finished
water from a surface water drinking plant, as summarized previously,
and approximately twofold to tenfold lower than the maximum peak
concentration of 32.2 ppb reported in the USGS-NAWQA data set.
Additional refined modeling assessments were based on a proposed
label submitted by FMC in May 2008. The refinements focused on two uses
currently allowed on the existing label that would have remained under
the withdrawn label: a corn rootworm rescue treatment, evaluated at 7
representative sites, and an at-plant
[[Page 44884]]
treatment for melons evaluated at 4 additional sites. EPA developed 5
additional corn scenarios 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, these assessments focused on the
corn rescue treatment (Ref. 4). Peak concentrations for the corn rescue
treatments simulated for Illinois, Iowa, Indiana, Kansas, Minnesota,
Nebraska, and Texas ranged from 16.6 - 36.7 ppb. For refinement of
estimates for the other use, melons, EPA developed 3 additional melon
scenarios representing states with extensive carbofuran usage at
locations more vulnerable than most in each state in areas melons are
grown. EPA used measured rainfall values and a wide row spacing to
simulate an application rate less than half of what is allowed as the
maximum rate for melons (0.65 versus 1.94 lb/A). Peak concentrations
resulting from a single ground application of carbofuran at plant in
Florida, Michigan, Missouri, and New Jersey resulted in peak
concentrations from 4.2 - 24.4 ppb (Id.). Additional details on these
assessments can be found at Ref. 4. Consistent with the analysis
summarized above these predicted carbofuran water concentrations are
similar to or lower than the peak concentrations reported in the USGS-
NAWQA monitoring data and similar to or not more than tenfold higher
than the 4 ppb reported in finished water from a surface water drinking
plant.
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. 42). 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 pathway for contamination of surface water. For
example, one study conducted in the United Kingdom in 1991 and 1992
looked at concentrations in tile drains and surface water treated at a
rate of 2.7 lbs a.i. per acre (granular formulation). Resulting
concentrations in surface water downstream of the field ranged from
49.4 ppb almost two months after treatment to 0.02 ppb 6 months later,
and were slightly lower than concentrations measured in the tile
drains, which were a transport pathway. Even with the factors that
limit the study's relevance to the majority of current carbofuran use--
the high use rate and granular formulation--the study clearly confirms
that tile drains can serve as a source of significant surface water
contamination. Although EPA's models do not account for tile drain
pathways, and acknowledging the uncertainties in comparing carbofuran
monitoring data to the concentrations predicted from the exposure
models, as noted previously, estimated (model-derived) peak
concentrations of carbofuran are similar to peak concentrations
reported in stream monitoring studies and are no more than tenfold
higher than a value reported from a drinking water plant where it is
unlikely the sample design would have ensured that water was sampled on
the day of the peak concentration.
EPA conducted dietary exposure analyses based on the modeling
scenarios for the current label as well as scenarios comparable to the
uses on FMC's proposed label of May 2008. Exposures from all modeled
scenarios substantially exceeded EPA's level of concern (Ref. 12). For
example, an Illinois corn scenario, assuming 2 foliar applications at a
typical 1-lb a.i. per acre use rate, estimated a 1-in-10-year peak
carbofuran water concentration of 26 ppb. Exposures at the 99.9th
percentile based on this modeled distribution ranged from 860% of the
aPAD for youths 13-19 to greater than 10,000% of the aPAD for infants.
This scenario is intended to be representative of highly vulnerable
sites on which corn could be grown on a national basis, and is used as
a screen for corn on a national basis. Similarly, exposures based on an
Idaho potato scenario, and using a 3 lb a.i. acre rate, ranged from
230% of the aPAD for children 6-12 to 890% of the aPAD for infants,
with a1-in-10-year peak carbofuran concentration of 10 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. More details on these assessments,
as well as the assessments EPA conducted for other crop scenarios, can
be found in Refs. 4, 12 and 47.
Table 8 below presents the results of one of EPA's refined exposure
analyses that addresses a use comparable to one in FMC's proposed May
2008 label. This example is based on a Nebraska corn rootworm ``rescue
treatment'' scenario, and assumes a single aerial application at a
typical rate of 1 pound a.i. per acre. To simulate an application made
post-plant, at or near rootworm hatch, EPA modeled an application of
carbofuran 30 days after crop emergence. EPA used a crop specific PCA
of 0.46 which is the maximum proportion of corn acreage in a Hydrologic
Unit Code 8-sized basin in the United States. (The U.S. Geological
Survey has classified all watersheds in the US into basins of various
sizes, according to hydrologic unit codes, in which the number of
digits indicates the size of the basin). 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. More details on these assessments, as well as the assessments EPA
conducted for other crop scenarios, can be found in Refs. 4, 12 and 47.
Table 8--Results of Acute Dietary (Surface Water Only) Exposure Analysis Incorporating the Nebraska Corn Rootworm Rescue Scenario
--------------------------------------------------------------------------------------------------------------------------------------------------------
95th Percentile 99th Percentile 99.9th Percentile
aPAD (mg/kg/-----------------------------------------------------------------------
Population Subgroup day) Exposure Exposure Exposure
(mg/kg/day) % aPAD (mg/kg/day) % aPAD (mg/kg/day) % aPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.000075 0.000444 590 0.001236 1,650 0.002912 3,900
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.000075 0.000190 250 0.000517 690 0.001267 1,700
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old 0.000075 0.000177 240 0.000473 630 0.001144 1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 44885]]
Children 6-12 years old 0.000075 0.000122 160 0.000329 440 0.000801 1,100
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old 0.0002 0.000091 45 0.000255 130 0.000671 340
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old 0.0002 0.000118 60 0.000313 160 0.000766 380
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old 0.0002 0.000125 60 0.000307 150 0.000671 340
--------------------------------------------------------------------------------------------------------------------------------------------------------
The populations described in the ``Nebraska corn'' assessments are
those people who consume water from a reservoir located in a small
watershed predominated by corn production (with the assumption that
treatment does not reduce carbofuran concentrations). The only crop
treated by carbofuran in the watershed is corn, and all of that crop is
assumed treated with carbofuran at the rate of 1 lb per acre. To the
extent a drinking water plant drawing water from the reservoir normally
treats the raw intake water with lime softening or activated carbon
processes the finished water concentrations could be reduced from 60 to
100% with the resultant aPADs ranging from approximately 460 to 102% of
the aPAD to 0% of the aPAD, respectively, at the 99.9th percentile of
exposure.
As discussed in the previous sections, it is important to remember
that carbofuran's aPAD is quite low, hence relatively low
concentrations of carbofuran monitored or estimated in surface water
can have a significant impact on the percent of the aPAD utilized.
Thus, while the refined carbofuran water concentrations for the corn
``rescue'' treatment in the range of approximately 16.6 to 36.7 ppb are
comparable to maximum peak concentrations reported in the monitoring
studies, these concentrations can result in very significant
exceedences of the aPAD for various age groups, primarily because
carbofuran is inherently very toxic.
FMC has criticized EPA's assessment for failing to account more
fully for the percent of the crop treated (PCT) in its modeling.
Uncertainty associated with PCT assumptions can be a major factor in
EPA's drinking water exposure assessment for surface-water sources.
Estimates of the percent of major crops (for example, corn) that are
treated with pesticides are available at the state level, but are
generally not available on a smaller scale suitable for estimating
drinking water exposure in a watershed. In addition, the PCT should be
assessed at a watershed-scale, aggregating all crops treated with the
pesticide in a watershed. If state-scale estimates are used to account
for PCT it will underestimate the risk for some of the drinking water
facilities in the state as the state-wide estimate represents an
average: values for individual facilities will be both lower and higher
than the state-wide estimate. In some cases, the underestimate can be
substantial if the application pattern tends to form cluster or pockets
of high usage. Insecticides like carbofuran are particularly prone to
this use pattern, as insect outbreaks often tend to be locally intense,
rather than widespread. In addition, marginal use practice changes in a
given watershed can substantially affect the percentage of the crop
treated, and such changes are effectively impossible to track. Without
data collected at a finer spatial scale, it is not possible to know
whether pesticide usage is evenly dispersed through the state or is
locally clustered. This results in large uncertainty in the drinking
water exposure assessments when percent crop treated is moderate or
low. Consequently, EPA does not typically include such information in
its surface-water exposure assessments.
However, 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 registrant
has at different times, suggested the application of a 5 or 10% crop
treated based on county sales data. While substantial questions remain
as to the support for these percentages for a given basin where
carbofuran may be used, EPA used the upper figure for the purpose of
conducting a sensitivity analysis. The results suggest that, even at
levels below 10% crop treated, exposures from drinking water derived
from surface waters can contribute significantly to the aggregate
dietary risks, particularly for infants and children. For example,
applying a 10% crop treated figure to the Nebraska corn scenario
described above, in addition to the corn-PCA of 0.46 incorporated into
that scenario, results in estimated exposures from water alone, ranging
from 110% of the aPAD for children 6-12 to 390% of the aPAD for
infants, assuming water treatment processes do not affect
concentrations in drinking water consumed. Details on the assessments
EPA conducted for other crop scenarios, which showed higher
contributions from drinking water, can be found in Refs. 12, 13 and 47.
Accordingly, these assessments suggest that EPA's use of PCA alone,
rather than in conjunction with PCT, will not meaningfully affect the
carbofuran risk assessment, as aggregate exposures would still exceed
100% of the aPAD.
In conclusion, the large difference between concentrations seen in
the monitoring data on the low side, and the simulation modeling on the
high side, is an indication of the uncertainty in the assessment for
surface-water source drinking water exposure. The majority of drinking
water concentrations resulting from use of carbofuran are likely to be
occurring at higher concentrations than those measured in most
monitoring studies, but below those estimated with simulation modeling;
however the exact values are highly uncertain. However, the monitoring
data show a consistent pattern of low concentrations, with the
occasional, infrequent spike of high concentrations. Those infrequent
high concentrations are consistent with EPA's modeling, which is
intended to capture the exposure peaks. For a chemical with an acute
risk, like carbofuran, the spikes or peaks in exposures, even though
infrequent, are the most relevant for assessing the risks. And, as
previously noted, the available monitoring has its own limitations for
estimating exposure for risk assessment.
Further, the results of the modeling analyses provide critical
insights
[[Page 44886]]
regarding locations in the country where the potential for carbofuran
contamination to surface water and associated drinking water sources
are more likely. These locations include areas with soils prone to
runoff (such as those high in clay or containing restrictive layers),
in regions with intensive agriculture with crops on which carbofuran is
used (e.g. corn), which have high rainfall amounts and/or are subject
to intense storm events in the spring around the times applications are
being made. Drinking water facilities with small basins tend to be more
vulnerable, as it is more likely that a large proportion of the crop
acreage will be treated in small basins.
Apparently FMC also has determined that some drinking water
facilities associated with surface source waters are vulnerable to
carbofuran exposure. In the now withdrawn labels FMC proposed to
require buffer zones around surface waters in certain locations of the
country, presumably to protect surface water. The proposed buffers were
for fields where soils were considered to be highly erodible. Buffers
were to be 66 feet wide and were to be vegetated with ``crop, seeded
with grass, or other suitable crop''. In 2000, EPA participated in the
development of a guidance document on how to reduce pesticide runoff
using conservation buffers (Ref. 55). Results of this effort found that
properly designed buffers can reduce runoff of weakly absorbed
pesticides like carbofuran by increasing filtration so that the
pesticide can be trapped and degraded in the buffer. However, it is of
critical importance that sheet flow be maintained across the buffer in
order for this to occur. To ensure sheet flow, buffers need to be
specifically designed for that purpose and they must be well-
maintained, as over time sediment trapped in the buffer causes flow to
become more channelized and the buffer then becomes ineffective. The
guidance concludes that un-maintained, un-vegetated buffers around
water bodies, often referred to a `setback,' are ineffective in
reducing pesticide movement to surface water.
3. Aggregate dietary exposures (food and drinking water). 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 concentrations of pesticides in source water fluctuate over time
and location for a variety of reasons. Pesticide residues in water
fluctuate daily, seasonally, and yearly as a result of the timing of
the pesticide application, 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. Consequently, EPA conducted several estimates of aggregate
dietary risks by combining exposures from food and drinking water. All
of these estimates showed that aggregate exposures to carbofuran
residues are unsafe. 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 Refs. 12 and 13.
Table 9 below reflects the results of aggregate exposures from food
and from drinking water derived from ground water in vulnerable areas
(i.e., from shallow wells associated with sandy soils and acidic
aquifers, such as are found in the Delmarva Peninsula). The estimates
range between 1,100% of the aPAD for adults, to over 10,000% of the
aPAD for infants.
Table 9--Results of Acute Dietary (Food and Water) Exposure Analysis Incorporating the Delmarva Ground Water Scenario
--------------------------------------------------------------------------------------------------------------------------------------------------------
95th Percentile 99th Percentile 99.9th Percentile
APAD (mg/kg/-----------------------------------------------------------------------
Population Subgroup day) Exposure Exposure Exposure
(mg/kg/day) % aPAD (mg/kg/day) % aPAD (mg/kg/day) % aPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.000075 0.003799 5,100 0.006026 8,000 0.010011 >10,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.000075 0.001622 2,200 0.002740 3,700 0.004644 6,200
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old 0.000075 0.001465 2,000 0.002414 3,200 0.004273 5,700
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old 0.000075 0.001026 1,400 0.001715 2,300 0.002825 3,800
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old 0.0002 0.000813 410 0.001442 720 0.002921 1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old 0.0002 0.000958 480 0.001638 820 0.003091 1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old 0.0002 0.000888 440 0.001351 680 0.002278 1,100
--------------------------------------------------------------------------------------------------------------------------------------------------------
The peak concentration estimates in the Delmarva groundwater
scenario time series are consistent with monitoring data from wells in
vulnerable areas where carbofuran was used. For example, the maximum
water concentration from the time series is 38.5 ppb while maximum
values from a targeted ground water monitoring study at the same site
was 65 ppb, with studies at other sites having similar or higher peak
concentrations (Refs. 13 and 47). For studies with multiple
measurements at each well, central tendency estimates were also in the
same range as the time series. For example, the mean carbofuran
concentration from wells under no-till agriculture in Queenstown, MD
was 7 ppb, while the median for the modeling was 15.5 ppb. The 90-day
average concentration, based on the registrant's PGW study conducted on
corn in the Delmarva (adjusted for current maximum application rates)
is 22 ppb.
Table 10 below presents the results of aggregate exposure from food
and derived from surface water using the Nebraska corn surface water
scenario. This table reflects the risks only for those people in
drinking watersheds with characteristics similar to that used in the
scenario, and assuming that water treatment does not remove carbofuran.
[[Page 44887]]
As discussed previously, the estimated water concentrations are
comparable to the maximum peak concentrations reported in monitoring
studies that were not designed to detect peak, daily concentrations of
carbofuran in vulnerable locations.
Table 10--Results of Acute Dietary (Food and Water) Exposure Analysis Using the Nebraska Corn Surface Water Scenario
--------------------------------------------------------------------------------------------------------------------------------------------------------
95th Percentile 99th Percentile 99.9th Percentile
aPAD (mg/kg/-----------------------------------------------------------------------
Population Subgroup day) Exposure Exposure Exposure
(mg/kg/day) % aPAD (mg/kg/day) % aPAD (mg/kg/day) % aPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.000075 0.000448 600 0.001240 1,700 0.002899 3,900
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.000075 0.000200 270 0.000533 710 0.001326 1,800
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old 0.000075 0.000187 250 0.000486 650 0.001190 1,600
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old 0.000075 0.000128 170 0.000336 450 0.000824 1,100
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old 0.0002 0.000095 48 0.000264 130 0.000685 340
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old 0.0002 0.000122 61 0.000318 160 0.000785 390
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old 0.0002 0.000129 65 0.000312 160 0.000689 340
--------------------------------------------------------------------------------------------------------------------------------------------------------
Typically, EPA's food and water exposure assessments 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 considered that it
might be appropriate to consider durations of exposure less than 24
hours. EPA has developed an analysis using information about external
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 information to estimate
the residual effects from carbofuran from previous exposures within the
day. The carbofuran analyses are described in the July 2008 aggregate
(dietary) memo (Ref. 12).
EPA has used two approaches for considering the impact of rapid
reversibility on exposure estimates in the food and drinking water risk
assessments. EPA previously used these approaches in the cumulative
risk assessment of the NMC pesticides and/or risk assessments for other
NMC pesticides (e.g., methomyl and aldicarb) (Ref. 63).
Incorporating eating occasion analysis and either the 150 minute or
300 minute recovery half life for carbofuran into the food only
analysis does not significantly change the risk estimates when compared
to baseline levels (for which a total daily consumption basis - and not
eating occasion - was used). From this, it is apparent that modifying
the analysis such that information on eating (i.e. food) occasions and
carbofuran half life is incorporated results in only minor reductions
in estimated risk.
The food analysis showed that over 70% of exposures at the top 0.2
percentile for children ages 1-2 and 3-5 are from a single eating event
of carbofuran indicating that carbofuran's food risk is not
substantively overstated. Moreover, when incorporating half-life to
recovery information, risks from summing exposures over 24 hours are
similar to those when incorporating half-life to recovery of 150 or 300
minutes. Regarding drinking water exposure, 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
reduced considerably--by a factor of two or more in some cases--
compared to baseline. This is not unexpected, as infants receive much
of their exposures from indirect drinking water in the form of water
used to prepare infant formula. 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 New Jersey melon
scenario, which estimated one of the lower exposure distributions,
aggregate exposures ranged from a low of 280% of the aPAD for infants,
based on a 150-minute half-life, to a high of 370% of the aPAD for
infants, based on a 300-minute half-life.
The two approaches discussed above are 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 to carbofuran is indeed not
substantively overestimated using the current exposure models and the
24-hour approach. This is due to the fact that exposure to carbofuran
occurs predominantly through single eating events and not from multiple
events that occur throughout the day. 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.
The result of all of these analyses clearly demonstrate that
aggregate exposure from all uses of carbofuran fail to meet the FFDCA
section 408 safety standard, and revocation of the associated
tolerances is warranted. Based on the contribution from food alone,
dietary exposures to carbofuran exceed EPA's level of concern for all
of the more sensitive subpopulations of infants and children. In
addition, EPA's analyses show that those individuals-both adults as
well as children--who receive their drinking water from vulnerable
sources are also 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 groundwater from 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
[[Page 44888]]
drinking water from reservoirs located in small agricultural
watersheds, prone to runoff, and predominated by crops that are treated
with carbofuran, although there is substantially more uncertainty
associated with these exposure estimates. Every sensitivity analysis
EPA has performed has shown that estimated exposures significantly
exceed EPA's level of concern for children. Although the magnitude of
the exceedance varies depending the level of conservatism in the
assessment, the fact that in each case, aggregate exposures from
dietary exposures of carbofuran fail to meet the FFDCA section 408
safety standard strongly corroborates EPA's conclusion that aggregate
exposures from all uses of carbofuran are not safe.
VII. When Do These Actions Become Effective?
The Agency is proposing that the revocations of the tolerances for
all commodities except artichoke and sunflower seed become effective 60
days after a final rule is published. EPA is also proposing to
establish an extended effective date for artichokes and sunflower seed,
to allow growers of these crops additional time to transition to
alternative compounds. The revocation for these two tolerances will
become effective two years after a final rule or order is published.
The Agency believes that these revocation dates will allow users to
exhaust stocks of carbofuran currently in their possession. However, if
EPA is presented with information during the comment period on this
proposal that end-users may need additional time to utilize carbofuran
stocks currently in their possession, and that information is verified,
the Agency will consider extending the expiration date of the
tolerance. If you have comments regarding the effective date, or if you
have comments on how long it would take you to utilize the carbofuran
stocks currently in your possession, please submit comments as
described under SUPPLEMENTARY INFORMATION.
Any commodities listed in this proposal treated with the pesticide
subject to this proposal, and in the channels of trade following the
tolerance revocations, shall be subject to FFDCA section 408(1)(5), as
established by FQPA. Under this section, any residues of these
pesticides in or on such food shall not render the food adulterated so
long as it is shown to the satisfaction of the Food and Drug
Administration that:
1. The residue is present as the result of an application or use of
the pesticide at a time and in a manner that was lawful under FIFRA,
and
2. The residue does not exceed the level that was authorized at the
time of the application or use to be present on the food under a
tolerance or exemption from tolerance. Evidence to show that food was
lawfully treated may include records that verify the dates when the
pesticide was applied to such food.
VIII. Are the Proposed Actions Consistent with International
Obligations?
The tolerance revocations in this proposal are not discriminatory
and are designed to ensure that both domestically-produced and imported
foods meet the food safety standard established by the FFDCA. The same
food safety standards apply to domestically produced and imported
foods.
EPA is working to ensure that the U.S. tolerance reassessment
program under FQPA does not disrupt international trade. EPA considers
Codex Maximum Residue Limits (MRLs) in setting U.S. tolerances and in
reassessing them. MRLs are established by the Codex Committee on
Pesticide Residues, a committee within the Codex Alimentarius
Commission, an international organization formed to promote the
coordination of international food standards. It is EPA's policy to
harmonize U.S. tolerances with Codex MRLs to the extent possible,
provided that the MRLs achieve the level of protection required under
FFDCA. EPA's effort to harmonize with Codex MRLs is summarized in the
tolerance reassessment section of individual Reregistration Eligibility
Decision documents. EPA has developed guidance concerning submissions
for import tolerance support (65 FR 35069, June 1, 2000) (FRL-6559-3).
This guidance will be made available to interested persons. Electronic
copies are available on the internet at http://www.epa.gov/. On the
Home Page select ``Laws, Regulations, and Dockets,'' then select
Regulations and Proposed Rules and then look up the entry for this
document under ``Federal Register--Environmental Documents.'' You can
also go directly to the ``Federal Register'' listings at http://www.epa.gov/fedrgstr/.
IX. Statutory and Executive Order Reviews
In this proposed rule, EPA is proposing to revoke specific
tolerances established under FFDCA section 408. The Office of
Management and Budget (OMB) has exempted this type of action (e.g.,
tolerance revocation for which extraordinary circumstances do not
exist) from review under Executive Order 12866, entitled Regulatory
Planning and Review (58 FR 51735, October 4, 1993). Because this
proposed rule has been exempted from review under Executive Order 12866
due to its lack of significance, this proposed rule is not subject to
Executive Order 13211, Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355,
May 22, 2001). This proposed rule does not contain any information
collections subject to OMB approval under the Paperwork Reduction Act
(PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or
contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor
does it require any special considerations as required by Executive
Order 12898, entitled Federal Actions to Address Environmental Justice
in Minority Populations and Low-Income Populations (59 FR 7629,
February 16, 1994); or OMB review or any other Agency action under
Executive Order 13045, entitled Protection of Children from
Environmental Health Risks and Safety Risks (62 FR 19885, April 23,
1997). This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
note). In addition, the Agency has determined that this action will not
have a substantial direct effect on States, on the relationship between
the national government and the States, or on the distribution of power
and responsibilities among the various levels of government, as
specified in Executive Order 13132, entitled Federalism (64 FR 43255,
August 10, 1999). Executive Order 13132 requires EPA to develop an
accountable process to ensure ``meaningful and timely input by State
and local officials in the development of regulatory policies that have
federalism implications.'' ``Policies that have federalism
implications'' is defined in the Executive order to include regulations
that have ``substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government.'' This proposed rule directly regulates growers, food
processors, food handlers and food retailers, not States. This
[[Page 44889]]
action does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of the FFDCA. For these same reasons, the Agency
has determined that this proposed rule does not have any ``tribal
implications'' as described in Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 6, 2000). Executive Order 13175, requires EPA to
develop an accountable process to ensure ``meaningful and timely input
by tribal officials in the development of regulatory policies that have
tribal implications.'' ``Policies that have tribal implications'' is
defined in the Executive order to include regulations that have
``substantial direct effects on one or more Indian tribes, on the
relationship between the Federal Government and the Indian tribes, or
on the distribution of power and responsibilities between the Federal
Government and Indian tribes.'' This proposed rule will not have
substantial direct effects on tribal governments, on the relationship
between the Federal Government and Indian tribes, or on the
distribution of power and responsibilities between the Federal
Government and Indian tribes, as specified in Executive Order 13175.
Thus, Executive Order 13175 does not apply to this proposed rule.
The Regulatory Flexibility Act (RFA) of 1980, as amended by the
Small Business Regulatory Enforcement Fairness Act of 1996 (SBREFA), 5
USC 601 et.seq, generally requires an agency to prepare a regulatory
flexibility analysis of any rule subject to notice and comment
rulemaking requirements under the Administrative Procedures Act or any
other statute. This is required unless the agency certifies that the
rule will not have a significant economic impact on a substantial
number of small entities. Small entities include small businesses,
small organizations, and small governmental jurisdictions. The Agency
has determined that no small organizations or small governmental
jurisdictions are impacted by today's rulemaking.
For purposes of assessing the impacts of today's determination on
businesses, a small business is defined either by the number of
employees or by the annual dollar amount of sales/revenues. The level
at which an entity is considered small is determined for each North
American Industry Classification System (NAICS) code by the Small
Business Administration (SBA). Farms are classified under NAICS code
111, Crop Production, and the SBA defines small entities as farms with
total annual sales of $750,000 or less.
The Agency has examined the potential effects today's proposed rule
may have on potentially impacted small businesses. Based on this
analysis, EPA concludes that the Agency can certify that revoking the
food tolerances for carbofuran will not have a significant economic
impact on a substantial number of small entities (No SISNOSE) for
alfalfa, artichoke, banana, chili pepper, coffee, cotton, cucurbits
(cucumber, melons, pumpkin, and squash), grape, grains (barley, flax,
oats, and wheat), field corn, potato, soybean, sorghum, sugarbeet,
sugarcane, sunflower, and sweet corn. Even in a worst-case scenario, in
which a grower obtains income only from a single crop and his/her
entire acreage is affected, the impact generally amounts to less than
2% of gross income and would be felt by fewer than 3% of affected small
producers. Estimates of impacts to corn growers were refined to account
for the sporadic nature of need for carbofuran while still maintaining
some assumptions that would bias the estimates upward. Refined
estimates were also made for artichoke and sunflower, which consider
the diversity in growers' revenue. The largest impact may be felt by
artichoke growers, with impacts as high as 5% of gross revenue, but
fewer than five growers are likely to be affected. EPA could not
quantify the impacts to banana, sugarcane, and sweet corn producers,
but the number of impacted farms is less than 2% of the farms subject
to the action. Additional detail on the analyses EPA conducted in
support of this certification can be found in Ref. 49.
X. 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 CAlocated 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.
1. Acute oral (gavage) dose range-finding study of cholinesterase
depression from carbofuran technical in juvenile (day 11) rats.
Hoberman, 2007. MRID 47143703 (unpublished FMC study) EPA-HQ-OPP-2007-
1088-0062.
2. Acute oral (gavage) time course study of cholinesterase
depression from carbofuran technical in adult and juvenile (day 11
postpartum) rats. Hoberman, 2007. MRID 47143704 (unpublished FMC study)
EPA-HQ-OPP-2007-1088-0063.
3. Additional chemographs for potatoes and cucurbits for drinking
water exposure assessment in support of the reregistration of
carbofuran (PC Code 090601) (R. David Jones, 10/23/07 D345729). EPA-HQ-
OPP-2005-0162-0486.
4. Additional refinements of the drinking water exposure assessment
for the use of carbofuran on corn and melons (PC code 090601)(R. David
Jones, 06/2008 D353714).
5. An In-Depth Investigation to Estimate Surface Water
Concentrations of Carbofuran within Indiana Community Water Supplies.
Performed by Waterborne Environmental, Inc., Leesburg, VA, Engel
Consulting, and Fawcett Consulting. Submitted by FMC. Corporation,
Philadelphia, PA. WEI No 528.01, FMC Report No. PC-0378. MRID 47221603.
EPA-HQ-OPP-2007-1088-0023.
6. An Investigation into the Potential for Carbofuran Leaching to
Ground Water Based on Historical and Current Use Practices. Submitted
by FMC. Corporation, Philadelphia, PA. Report No. PC-0363. MRID
47221602. EPA-HQ-OPP-2007-1088-0022.
7. An Investigation into the Potential for Carbofuran Leaching to
Ground Water Based on Historical and Current Use Practices:
Supplemental Report on Twenty-one Additional States. Submitted by FMC
Corporation, Philadelphia, PA. Report No. PC-0383. MRID 47244901. EPA-
HQ-OPP-2007-1088-0025.
8. Benchmark dose analysis of cholinesterase inhibition data in
neonatal and adult rats (MRID no. 46688914) following exposure to
carbofuran (A.Lowit, 1/19/06, D325342, TXR no. 0054034). EPA-HQ-OPP-
2007-1088-0045.
9. Benjamins, J.A. and McKhann, G.M. (1981) Development,
regeneration, and aging of the brain. In: Basic Neurochemistry, 3rd
edition. Edited by Siegel, G.J., Albers, R.W., Agranoff, B.W., and
Katzman, R. Little, Brown and Co., Boston. pp 445-469; Dobbing, J. and
Smart, J.L. (1974) Vulnerability of developing brain and behaviour.
British Medical Bulletin. 30:164-168; Davison, A.N. and Dobbing, J.
(1966) Myelination as a vulnerable period in brain development. British
Medical Bulletin. 22:40-44.
[[Page 44890]]
10. Best Management Practices to Reduce Carbofuran Losses to Ground
And Surface Water. Submitted by FMC. Corporation, Philadelphia, PA.
Report No. PC-0362. MRID 47279201. EPA-HQ-OPP-2005-0162-0464.
11. California Department of Pesticide Regulation. Risk
Characterization Document for Carbofuran. January 23, 2006. 219 pgs.
12. Carbofuran Acute Aggregate Dietary (Food and Drinking Water)
Exposure and Risk Assessments for the Reregistration Eligibility
Decision (T. Morton, 7/22/08, D351371).
13. Carbofuran Environmental Risk Assessment and Human Drinking
Water Exposure Assessment for IRED. March 2006. EPA-HQ-OPP-2005-0162-
0080.
14. Carringer, 2000. Carbamate Market Basket Survey. Reviewed by S.
Piper, D267539, 8/8/02. (MRID 45164701 S. Carringer, 5/12/00).
15. Carbofuran. HED Revised Risk Assessment for the Reregistration
Eligibility Decision (RED) Document (Phase 6). (PC 090601) D 330541,
July 26, 2006. EPA-HQ-OPP-2005-0162-0307.
16. Carbofuran. HED Revised Risk Assessment for the Notice of
Intent to Cancel. (PC 090601) D 347038, January 2007. EPA-HQ-OPP-2007-
1088-0034.
17. Cholinesterase depression in juvenile (day 11) and adult rats
following acute oral (gavage) dose of carbofuran technical. Hoberman,
2007. MRID 47143705 (unpublished FMC study). EPA-HQ-OPP-2007-1088-0066.
18. Context Document for Carbofuran Risk Assessment Issues not
Specifically Addressed in the FIFRA SAP Charge Questions (M. Panger, C.
Salice, R. David Jones, E. Odenkirchen, I. Sunzenauer, 1/08 D348292).
EPA-HQ-OPP-2007-1088-0071.
19. Data Evaluation Record for Acute dose-response study of
carbofuran technical administered by gavage to adult and postnatal day
11 male and female CD[reg](Sprague-Dawley) rats. MRID 46688914. EPA-HQ-
OPP-2007-1088-0045.
20. Data Evaluation Record for Cholinesterase depression in
juvenile (day 11) and adult rats following acute oral (gavage) dose of
carbofuran technical. MRID 47143705.
21. Dose-time response modeling of rat brain AChE activity:
carbofuran gavage dosing 10/5/07 (Carbofuran-RatBrainDR.pdf) EPA-HQ-
OPP-2007-1088-0053.
22. Dose-time response modeling of rat RBC-AChE activity:
carbofuran gavage dosing 10/23/07 (RatRBC--DR.pdf). EPA-HQ-OPP-2007-
1088-0029.
23. EPA Response to the Transmittal of Meeting Minutes of the FIFRA
Scientific Advisory Panel Meeting Held February 5-8 2008 on the
Agency's Proposed Action under FIFRA 6(b) Notice of Intent to Cancel
Carbofuran (E.Reaves, A. Lowit, J. Liccione 7/2008 D352315).
24. Estimated Drinking Water Concentrations (email communication
D.Young to D.Drew, 3/8/06).
25. FIFRA SAP (1998) ``A set of Scientific Issues Being Considered
by the Agency in Connection with Proposed Methods for Basin-scale
Estimation of Pesticide Concentrations in Flowing Water and Reservoirs
for Tolerance Reassessment.'' Final Report from the FIFRA Scientific
Advisory Panel Meeting of July 29-30, 1998 (Report dated September 2,
1998). Available at: http://www.epa.gov/scipoly/sap/meetings/1998/july/final1.pdf.
26. FIFRA SAP (1999) ``Sets of Scientific Issues Being Considered
by the Environmental Protection Agency Regarding Use of Watershed-
derived Percent Crop Areas as a Refinement Tool in FQPA Drinking Water
Exposure Assessments for Tolerance Reassessment.'' Final Report from
the FIFRA Scientific Advisory Panel Meeting of February 5-7, 2002
(Report dated May 25, 1999). SAP Report 99-03C. Available at: http://www.epa.gov/scipoly/sap/meetings/1999/may/final.pdf.
27. FIFRA SAP. (2002). ``Methods Used to Conduct a Preliminary
Cumulative Risk Assessment for Organophosphate Pesticides.'' Final
Report from the FIFRA Scientific Advisory Panel Meeting of February 5-
7, 2002 (Report dated March 19, 2002). FIFRA Scientific Advisory Panel,
Office of Science Coordination and Policy, Office of Prevention,
Pesticides and Toxic Substances, U.S. Environmental Protection Agency.
Washington, DC. SAP Report 2002-01.
28. FIFRA Science Advisory Panel (SAP). 2005a. ``Final report on N-
Methyl Carbamate Cumulative Risk Assessment: Pilot Cumulative
Analysis.'' Final Report from the FIFRA Scientific Advisory Panel
Meeting of February , 2005 (Report dated September 2, 1998). Available
at: http://www.epa.gov/scipoly/sap/2005/february/minutes.pdf .
29. FIFRA Science Advisory Panel (SAP). 2005b. ``Final report on
Preliminary N-Methyl Carbamate Cumulative Risk Assessment.'' Final
Report from the FIFRA Scientific Advisory Panel Meeting of July 29-30,
1998 (Report dated September 2, 1998). Available at: http://www.epa.gov/scipoly/sap/2005/august/minutes.pdf.
30. FIFRA Science Advisory Panel (SAP). 2008. ``Final report on the
Agency's Proposed Action under FIFRA 6(b) Notice of Intent to Cancel
Carbofuran.'' Report from the FIFRA Scientific Advisory Panel Meeting
of February , 5-8 2008 (Report dated September 2, 1998). Available at:
http://www.epa.gov/scipoly/sap/meetings/2008/february/carbofuransapfinal.pdf.
31. Final report on cholinesterase inhibition study of carbofuran:
PND17 rats. MRID 47167801 (ORD study). EPA-HQ-OPP-2007-1088-0064.
32. FMC Letter Requesting Proposed Label Amendments and Voluntary
Cancellations. Dated May 9, 2008. EPA-HQ-OPP-2005-0162-0496 and -0497.
Email Communication from John Cummings to Steven Bradbury, dated June
10, 2008. EPA-HQ-OPP-2005-0162-0499.
33. Hunter, D.L., Marshall, R.S., and Padilla, S. (1997). Automated
instrument analysis of cholinesterase activity in tissues from
carbamate-treated animals: A cautionary note. Toxicology Mechanisms and
Methods, 7:43-53.
34. Interim Reregistration Eligibility Decision for Carbofuran. D.
Edwards. 2006. Regulations.gov document number: EPA-HQ-OPP-2005-0162-
0304.
35. IPCS World Health Organization. 2005. Chemical Specific
Adjustment factors for Interspecies Differences and Human Variability:
Guidance Document for use of Data in Dose/Concentration-Response
Assessment.
36. Issue Paper for the FIFRA SAP Meeting on Carbofuran: Human
Health Risk Assessment Reregistration Eligibility Science Chapter for
Carbofuran, Environmental Fate and Effects Chapter. March 2006. EPA-HQ-
OPP-2007-1088-0031.
37. Johnson, C.D. and Russell, R.L. (1975) A rapid, simple
radiometric assay for cholinesterase, suitable for multiple
determinations. Analytical Biochemistry. 64:229-238.
38. McDaniel K.L. and Moser V.C. (2004) Differential profiles of
cholinesterase inhibition and neurobehavioral effects in rats exposed
to fenamiphos or profenofos. Neurotoxicology and Teratology. 26:407-
415.
39. McDaniel K.L., Padilla S., Marshall R.S., Phillips P.M.,
Podhorniak L., Qian Y., Moser V.C. (2007) Comparison of acute
neurobehavioral and cholinesterase inhibitory effects of N-methyl
carbamates in rats. Toxicology Sciences. 98, 552-560.
40. Moser V.C. (1995) Comparisons of the acute effects of
cholinesterase inhibitors using a neurobehavioral
[[Page 44891]]
screening battery in rats. Neurotoxical and Teratology 17: 617-625.
41. National Assessment of the Relative Vulnerability of Community
Water Supply Reservoirs in Carbofuran Use Areas. Performed by
Waterborne Environmental Inc., Leesburg, VA and Engel Consulting, West
Lafayette, IN. Submitted by FMC Corporation, Philadelphia, PA. WEI
Report No. 528.01-B, FMC Report No. PC-0387. MRID 47272301. EPA-HQ-OPP-
2007-1088-0024.
42. National Resources Inventory 1992, cited in USGS 2002,
``Herbicide Concentrations in the Mississippi River Basin--the
importance of chloracetanilide degradates.'' R.A. Rebich, R.H. Coupe,
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43. Nostrandt, A.C., Duncan, J.A., and Padilla, S. (1993). A
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course of cholinesterase inhibition in adult rats treated acutely with
carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl, or
propoxur. Toxicology and Applied Pharmacology, 219; 202-209.
45. PND17 BMDs and BMDLs and recovery half-lives for the effects of
carbofuran on brain and blood AChE (PND17--DR.pdf). EPA-HQ-OPP-2007-
1088-0047.
46. Report on cholinesterase sensitivity study of carbofuran: Adult
and PND11 MRID 47289001 (ORD study). EPA-HQ-OPP-2007-1088-0065.
47. Revised Drinking Water Assessment in Support of the
Reregistration of Carbofuran (PC Code 090601) (R. David Jones, 9/5/07
D3424057). EPA-HQ-OPP-2005-0162-0485.
48. Revised HED Product Chemistry and Residue Chemistry Chapter of
the RED (D. Drew, 1/13/05, D306796). EPA-HQ-OPP-2005-0162-0028.
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half-lives for the effect of Carbofuran on brain and blood AChE. 12
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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: July 23, 2008.
Debra Edwards,
Director, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR chapter I be amended as
follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.254 is amended by revising the table in paragraph
(a) and the table in paragraph (c), and by removing paragraph (d) to
read as follows.
Sec. 180.254 Carbofuran; tolerances for residues.
(a) * * *
------------------------------------------------------------------------
Expiration/
Commodity Parts per Revocation
million Date
------------------------------------------------------------------------
Sunflower, seed (of which no more than 0.2 ppm 1.0 10/31/10
is carbamate)
------------------------------------------------------------------------
* * * * *
(c) * * *
[[Page 44892]]
------------------------------------------------------------------------
Expiration/
Commodity Parts per Revocation
million Date
------------------------------------------------------------------------
Artichoke, globe (of which no more than 0.2 0.4 10/31/10
ppm is carbamate)
------------------------------------------------------------------------
[FR Doc. E8-17660 Filed 7-29-08; 1:15 pm]
BILLING CODE 6560-50-S