[Federal Register: March 14, 2007 (Volume 72, Number 49)]
[Rules and Regulations]
[Page 11777-11784]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14mr07-4]
=======================================================================
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2005-0312; FRL-8113-6]
Prothioconazole; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes tolerances for combined residues
of prothioconazole and prothioconazole-
[[Page 11778]]
desthio calculated as parent in or on barley, grain/hay/straw; grain,
aspirated grain fractions; pea and bean, dried shelled, except
soybeans, subgroup 6C; peanut; peanut hay; rapeseed, seed; wheat,
grain/forage/hay/straw; and for combined residues of prothioconazole,
prothioconazole-desthio and conjugates that can be converted to these
two compounds by acid hydrolysis, calculated as parent in or on cattle,
meat/meat byproducts/fat/milk; poultry, liver; goat, fat/meat/meat
byproducts; hog, meat byproducts; horse, fat/meat/meat byproducts;
sheep, fat/meat/meat byproducts. Bayer CropScience requested tolerances
under the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by
the Food Quality Protection Act of 1996 (FQPA).
DATES: This regulation is effective March 14, 2007. Objections and
requests for hearings must be received on or before May 14, 2007, and
must be filed in accordance with the instructions provided in 40 CFR
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2005-0312. To access the
electronic docket, go to http://www.regulations.gov, select ``Advanced
Search,'' then ``Docket Search.'' Insert the docket ID number where
indicated and select the ``Submit'' button. Follow the instructions on
the regulations.gov website to view the docket index or access
available documents. All documents in the docket are listed in the
docket index available in regulations.gov. Although listed in the
index, some information is not publicly available, e.g., Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available in the electronic docket at http://www.regulations.gov, or,
if only available in hard copy, at the OPP Regulatory Public Docket in
Rm. S-4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr.,
Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The Docket Facility
telephone number is (703) 305-5805.
FOR FURTHER INFORMATION CONTACT: Tony Kish, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-9443; e-mail address: kish.tony@epa.gov.
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), e.g., agricultural
workers; greenhouse, nursery, and floriculture workers; farmers.
Animal production (NAICS code 112), e.g., cattle ranchers
and farmers, dairy cattle farmers, livestock farmers.
Food manufacturing (NAICS code 311), e.g., agricultural
workers; farmers; greenhouse, nursery, and floriculture workers;
ranchers; pesticide applicators.
Pesticide manufacturing (NAICS code 32532), e.g.,
agricultural workers; commercial applicators; farmers; greenhouse,
nursery, and floriculture workers; residential users.
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at http://www.regulations.gov
, you may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of 40 CFR part 180 through the
Government Printing Office's pilot e-CFR site at http://www.gpoaccess.gov/ecfr
.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of FFDCA, as amended by FQPA, any person may
file an objection to any aspect of this regulation and may also request
a hearing on those objections. The EPA procedural regulations which
govern the submission of objections and requests for hearings appear in
40 CFR part 178. You must file your objection or request a hearing on
this regulation in accordance with the instructions provided in 40 CFR
part 178. To ensure proper receipt by EPA, you must identify docket ID
number EPA-HQ-OPP-2005-0312 in the subject line on the first page of
your submission. All requests must be in writing, and must be mailed or
delivered to the Hearing Clerk on or before May 14, 2007.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit your copies, identified by docket ID
number EPA-HQ-OPP-2005-0312, 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
Bldg.), 2777 S. Crystal Dr., 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 Facility telephone number is (703) 305-5805.
II. Background and Statutory Findings
In the Federal Register of November 30, 2005 (70 FR 71831) (FRL-
7747-6), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
4F6830) by Bayer CropScience, 2 T.W. Alexander Dr., Research Triangle
Park, NC 27709. The petition requested that 40 CFR part 180 be amended
by establishing tolerances for residues of the fungicide
prothioconazole, 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-
hydroxypropyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, in or on barley,
grain at 0.2 parts per million (ppm); barley, hay at 7.0 ppm; barley,
straw at 2.0 ppm; barley, pearled at 0.2 ppm; barley, bran at 0.4 ppm;
black mustard, seed at
[[Page 11779]]
0.1 ppm; borage, seed at 0.1 ppm; canola, seed at 0.1 ppm; crambe, seed
at 0.1 ppm; field mustard, seed at 0.1 ppm; flax, seed at 0.1 ppm;
grain, aspirated fractions at 13.0 ppm; Indian mustard, seed at 0.1
ppm; Indian rapeseed 0.1 ppm; pea and bean, dried shelled (except
soybeans) at 0.8; peanut, nutmeat at 0.02 ppm; peanut, hay at 5.0 ppm;
peanut, meal at 0.3 ppm; rapeseed, seed at 0.1 ppm; rice, grain at 0.25
ppm; rice, straw at 1.5 ppm; rice, hulls at 1.0 ppm; wheat, grain at
0.06 ppm; wheat, bran at 1.5 ppm; wheat, forage at 7.0 ppm; wheat, germ
at 0.15 ppm; wheat, hay at 4.0 ppm; wheat, straw at 2.3 ppm and for
combined residues of prothioconazole, its desthio and 4-hydroxy
metabolites, and conjugates of each in cattle, meat at 0.01 ppm;
cattle, meat byproducts at 1.2 ppm; cattle, fat at 0.1 ppm; and milk at
0.006 ppm. That notice included a summary of the petition prepared by
Bayer CropScience, the registrant. Comments were received on the notice
of filing. EPA's response to these comments is discussed in Unit IV.C.
For the reasons stated in Unit V., EPA is not establishing at this
time the following petitioned-for tolerances: Rice; black mustard;
borage; flax; Indian mustard; barley, pearled barley; barley, bran;
canola; crambe; field mustard; Indian rapeseed; peanut, meal; wheat,
bran; and wheat, germ.
Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical
residue....''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 of FFDCA and a complete
description of the risk assessment process, see http://www.epa.gov/oppfead1/trac/science
.
III. Aggregate Risk Assessment and Determination of 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 has sufficient data to assess the hazards of and to
make a determination on aggregate exposure, consistent with section
408(b)(2) of FFDCA, for a tolerance for combined residues of
prothioconazole and prothioconazole-desthio, calculated as parent in or
on barley, grain at 0.35 ppm; barley, hay at 7.0 ppm; barley, straw at
4.0 ppm; grain, aspirated grain fractions at 11.0 ppm; pea and bean,
dried shelled, except soybeans, subgroup 6C at 0.9; peanut at 0.02 ppm;
peanut, hay at 6.0 ppm; rapeseed, seed at 0.15 ppm; wheat, grain at
0.07 ppm; wheat, forage at 6.0 ppm; wheat, hay at 4.5 ppm; wheat, straw
at 5.0 ppm and for combined residues of prothioconazole,
prothioconazole-desthio, and conjugates that can be converted to these
two compounds by acid hydrolysis, calculated as parent in or on cattle,
meat at 0.02 ppm; cattle, meat byproducts at 0.2 ppm; cattle, fat at
0.1 ppm; goat, fat at 0.1 ppm; goat, meat at 0.02 ppm; goat, meat
byproducts at 0.2 ppm; hog, meat byproducts at 0.05 ppm; horse, fat at
0.1 ppm; horse, meat at 0.02 ppm; horse, meat byproducts at 0.2 ppm;
milk at 0.02 ppm; poultry, liver at 0.02 ppm; sheep, fat at 0.1 ppm;
sheep, meat at 0.02 ppm and sheep, meat byproducts at 0.2 ppm.
EPA's assessment of exposures and risks associated with
establishing the tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. Specific information on the studies received and the nature
of the toxic effects caused by prothioconazole as well as the no-
observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-
effect-level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov
.
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, the dose at which no adverse effects are observed
(the NOAEL) from the toxicology study identified as appropriate for use
in risk assessment is used to estimate the toxicological level of
concern (LOC). However, the lowest dose at which adverse effects of
concern are identified (the LOAEL) is sometimes used for risk
assessment if no NOAEL was achieved in the toxicology study selected.
An uncertainty factor (UF) is applied to reflect uncertainties inherent
in the extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify non-threshold hazards such as
cancer. The Q* approach assumes that any amount of exposure will lead
to some degree of cancer risk, and estimates risk in terms of the
probability of occurrence of additional cancer cases. More information
can be found on the general principles EPA uses in risk
characterization at:
1. http://www.epa.gov/oppfead1/trac/science 2. http://www.epa.gov/pesticides/factsheets/riskassess.htm.
.htm.
Both prothioconazole and prothioconazole-desthio have low acute
toxicities by oral, dermal, and inhalation routes. Neither compound is
a dermal sensitizer, nor a skin or eye irritant.
Subchronic toxicity studies show that the target organs at the
LOAEL include the liver, kidney, urinary bladder, thyroid, and blood.
NOAEL/LOAEL values across the family of chemicals (i.e.,
prothioconazole, and metabolites prothioconazole-desthio, and
prothioconazole sulfonic acid potassium salt) in the toxicity database
indicate that prothioconazole-desthio is a more toxic chemical.
The profile of chronic toxicity is similar to that of subchronic
toxicity, and also includes body weight and food consumption changes,
and toxicity to the lymphatic and gastrointestintal (GI) systems. The
relative potency of prothioconazole-desthio is greater than
prothioconazole.
The data from developmental toxicity studies indicate that
prothioconazole and the three metabolites evaluated (i.e.,
prothioconazole-desthio, prothioconazole sulfonic acid potassium salt,
and prothioconazole-deschloro) variously produce prenatal developmental
effects at levels equal to or below maternally toxic levels.
Prothioconazole-desthio is a developmental neurotoxicant,
[[Page 11780]]
producing changes in brain morphometrics and increases in the
occurrence of peripheral nerve lesions in the neonate. A NOAEL was not
determined, since these observations were looked for only at the high
dose level. Prothioconazole-desthio is the most toxic orally or
dermally, with LOAELs significantly below that of the other chemicals.
In reproduction studies in the rat, conducted using prothioconazole
and prothioconazole-desthio, reproductive and offspring toxicities are
observed only in the presence of parental toxicity. The nature of
parental toxicity is similar to what was observed in the subchronic
studies, such as body weight and food consumption changes, liver
effects, etc. Reproductive effects include decreases in reproductive
indices such as those that indicate pup survival and growth. Offspring
toxicity is manifested by decreased pup weights and malformations such
as cleft palate. The data show that prothioconazole-desthio is more
toxic by an order of magnitude.
Acute and subchronic neurotoxicity studies were conducted in the
rat using prothioconazole. The acute neurotoxicity study produced
reduced motor and locomotor activity at a relatively high dose level,
while no neurotoxicity was observed in the subchronic neurotoxicity
study. As mentioned in the discussion of developmental toxicity, a
developmental neurotoxicity study was conducted in the rat using
prothioconazole-desthio, and neurotoxic effects were at the high dose
level only were included in the report. Judging from these three
neurotoxicity studies, prothioconazole-desthio is the more potent
neurotoxicant, which is consistent with its relative potency in other
areas of toxicity.
A battery of mutagenicity studies was conducted using both
prothioconazole and its desthio metabolite. In addition,
carcinogenicity studies were conducted in rats and mice using these two
chemicals. The available data indicate that neither of these compounds
is mutagenic or carcinogenic in the species tested, which mitigates
against concern for carcinogenicity in humans.
A summary of the toxicological endpoints for prothioconazole used
for human risk assessment is shown in Table 1 of this unit:
Table 1.--Summary of Toxicological Dose and Endpoints for Prothioconazole for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
Dose used in risk
assessment, FQPA safety factor (SF)
Exposure/scenario interspecies and and level of concern Study and toxicological
intraspecies and any for risk assessment effects
traditional UF
----------------------------------------------------------------------------------------------------------------
Acute dietary NOAEL = 2.0 milligram/ FQPA SF = 10X Developmental Toxicity
(Females 13-49 years of age)......... kilogram/day (mg/kg/ acute population study in rabbits
day) adjusted dose (aPAD) = LOAEL = 10 mg/kg/day
UF = 100 X acute acute RfD/Special FQPA based on structural
reference dose (RfD) = SF = 0.002 mg/kg/day. alterations including
0.002 mg/kg/day. malformed vertebral
body and ribs,
arthrogryposis, and
multiple malformations
----------------------------------------------------------------------------------------------------------------
Chronic dietary NOAEL= 1.1 mg/kg/day FQPA SF = 10X Chronic/Oncogenicity
(All populations).................... UF = 100 X chronic RfD chronic population study in rats
= 0.001 mg/kg/day. adjusted dose (cPAD) = LOAEL = 8.0 mg/kg/day
chronic RfD/FQPA SF = based on liver
0.001 mg/kg/day. histopathology
(hepatocellular
vacuolation and fatty
change (single cell,
centrilobular, and
periportal))
----------------------------------------------------------------------------------------------------------------
Cancer Classification: ``Not likely to be Carcinogenic to Humans'' based on the
(Oral, dermal, inhalation)........... absence of significant tumor increases in two adequate rodent
carcinogenicity studies.
----------------------------------------------------------------------------------------------------------------
Note: The toxicity endpoints for prothioconazole-desthio were used for the prothioconazole risk assessment
because they were slightly more conservative than those for prothioconazole per se.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have not
been previously established for the combined residues of
prothioconazole and prothioconazole-desthio, calculated as parent, in
or on a variety of raw agricultural commodities and combined residues
of prothioconazole and prothioconazole-desthio and conjugates that can
be converted to these two compounds by acid hydrolysis, calculated as
parent, in or on milk and edible animal products. Risk assessments were
conducted by EPA to assess dietary exposures from prothioconazole in
food as follows:
i. Acute exposure. Quantitative acute dietary exposure and risk
assessments are performed for a food-use pesticide, if a toxicological
study has indicated the possibility of an effect of concern occurring
as a result of a 1-day or single exposure.
In conducting the acute dietary exposure assessment EPA used the
Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database (DEEM-FCID\TM\, version 2.03), which incorporates food
consumption data as reported by respondents in the U.S. Department of
Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of
Food Intake by Individuals (CSFII), and accumulated exposure to the
chemical for each commodity. The following assumptions were made for
the acute exposure assessments: A moderately refined acute dietary
exposure assessment was conducted for prothioconazole. Empirical
processing factors (PFs) and livestock maximum residues were
incorporated, and 100 percent crop treated (PCT) was assumed for the
acute assessment. Average residue levels were also used, since all of
the plant commodities included in this assessment are blended food
forms.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used DEEM-FCID\TM\, version 2.03, which incorporates
food consumption data as reported by respondents in the USDA 1994-1996
and 1998 CSFII, and accumulated exposure to the chemical for each
commodity. The following assumptions were made for the chronic exposure
assessments: A moderately refined chronic dietary exposure
[[Page 11781]]
assessment was performed. Empirical PFs, average residues, and
livestock maximum residues were incorporated into the chronic
assessment and 100 PCT was assumed.
iii. Cancer. The Agency classified prothioconazole and/or its
metabolites as ``Not likely to be Carcinogenic to Humans'' according to
the 2005 Cancer Guidelines, based on available studies in the mouse and
rat that showed no increase in tumor incidence. Accordingly, no
exposure assessment is necessary for assessing cancer risk.
iv. Anticipated residue and PCT information. For assessment of
acute dietary risk, empirical PFs and livestock maximum residues were
incorporated, and 100 PCT was assumed for the acute assessment. Average
residue levels were also used, since all of the plant commodities
included in this assessment are blended food forms. Likewise for the
assessment of chronic dietary risk, empirical PFs, average residues,
and livestock maximum residues were incorporated into the chronic
assessment and 100 PCT was also assumed.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for prothioconazole in drinking
water. Because the Agency does not have comprehensive monitoring data,
drinking water concentration estimates are made by reliance on
simulation or modeling taking into account data on the physical
characteristics of prothioconazole. Further information regarding EPA
drinking water models used in pesticide exposure assessment can be
found at http://www.epa.gov/oppefed1/models/water/index.htm.
Based on the Pesticide Root Zone Model/Exposure Analysis Modeling
System (PRZM/EXAMS) and Screening Concentration in Groundwater (SCI-
GROW) models, the estimated drinking water concentrations (EDWCs) of
prothioconazole for acute exposures are estimated to be 22 parts per
billion (ppb) for surface water. The EDWCs for chronic exposures are
estimated to be 11 ppb for surface water. EPA used the EDWCs for
surface water in assessing the risk from prothioconazole because the
EWDCs for ground water are minimal in comparison to surface water.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
Prothioconazole is not registered for use on any sites that would
result in residential exposure.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
Prothioconazole is a member of the triazole-containing class of
pesticides. Although conazoles act similarly in plants (fungi) by
inhibiting ergosterol biosynthesis, there is not necessarily a
relationship between their pesticidal activity and their mechanism of
toxicity in mammals. Structural similarities do not constitute a common
mechanism of toxicity. Evidence is needed to establish that the
chemicals operate by the same, or essentially the same, sequence of
major biochemical events. In conazoles, however, a variable pattern of
toxicological responses is found. Some are hepatotoxic and
hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some
induce developmental, reproductive, and neurological effects in
rodents. Furthermore, the conazoles produce a diverse range of
biochemical events including altered cholesterol levels, stress
responses, and altered DNA methylation. It is not clearly understood
whether these biochemical events are directly connected to their
toxicological outcomes. Thus, there is currently no evidence to
indicate that conazoles share common mechanisms of toxicity and EPA is
not following a cumulative risk approach based on a common mechanism of
toxicity for the conazoles. For information regarding EPA's procedures
for cumulating effects from substances found to have a common mechanism
of toxicity, see EPA's website at http://www.epa.gov/pesticides/cumulative
.
Prothioconazole is a triazole-derived pesticide. This class of
compounds can form the common metabolite 1,2,4-triazole and two
triazole conjugates (triazolylalanine and triazolylacetic acid). To
support existing tolerances and to establish new tolerances for
triazole-derivative pesticides, including prothioconazole, EPA
conducted a human health risk assessment for exposure to 1,2,4-
triazole, triazolylalanine, and triazolylacetic acid resulting from the
use of all current and pending uses of any triazole-derived fungicide.
The risk assessment is a highly conservative, screening-level
evaluation in terms of hazards associated with common metabolites
(e.g., use of a maximum combination of UFs) and potential dietary and
non-dietary exposures (i.e., high-end estimates of both dietary and
non-dietary exposures). In addition, the Agency retained the additional
10X FQPA SF for the protection of infants and children. The assessment
includes evaluations of risks for various subgroups, including those
comprised of infants and children. The Agency's complete risk
assessment is found in the propiconazole reregistration docket at
http://www.regulations.gov, docket ID number EPA-HQ-OPP-2005-0497.
D. Safety Factor for Infants and Children
1. In general. Section 408 of 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 database on toxicity and exposure
unless EPA determines based on reliable data that a different margin of
safety will be safe for infants and children. Margins of safety are
incorporated into EPA risk assessments either directly through use of a
MOE analysis or through using uncertainty (safety) factors in
calculating a dose level that poses no appreciable risk to humans. In
applying this provision, EPA either retains the default value of 10X
when reliable data do not support the choice of a different factor, or,
if reliable data are available, EPA uses a different additional SF
value based on the use of traditional UFs and/or special FQPA SFs, as
appropriate.
2. Prenatal and postnatal sensitivity--i. Prenatal. Available
evidence from rat developmental toxicity studies with prothioconazole
(oral) and its desthio (oral and dermal) and sufonic acid K salt (oral)
metabolites, rabbit developmental with desthio metabolite (oral), and
rat developmental neurotoxicity with desthio metabolite (oral), as well
as a multi-generation reproduction study with the desthio metabolite,
indicate that there is concern for prenatal toxicity. Effects include
skeletal structural abnormalities, such as cleft palate, deviated
snout, malocclusion, and extra ribs; developmental delays; other
effects include changes in brain morphometry, peripheral nerve lesions,
and death.
ii. Postnatal. Available data also show that the skeletal effects
such as extra ribs are not completely reversible after birth in the
rat, but persist as development continues. Data from the developmental
neurotoxicity study also show that brain morphometry is
[[Page 11782]]
abnormal postnatally, and there is an increased incidence of lesions of
the peripheral nerves postnatally.
3. Conclusion. The toxicity database for prothioconazole (and its
metabolites) is adequate for endpoint selection for exposure risk
assessment scenarios and for FQPA evaluation, with the exception of
missing data on brain morphometry at lower does from the developmental
neurotoxicity study. Effects are seen in the 2-generation reproduction
studies in rats; developmental studies in rats and rabbits; and a
developmental neurotoxicity study in rats which suggest that pups are
more susceptible: Pup effects were seen at levels below the LOAELs for
maternal toxicity and, in general, were of comparable or greater
severity compared to the effects observed in adults. Additionally,
there is uncertainty concerning the LOAEL/NOAEL for developmental
effects seen in the developmental neurotoxicity study in rats (abnormal
brain morphometry at high dose) due to a lack of information on brain
morphometry at lower doses. Given that both quantitative and
qualitative sensitivity was observed in pups in several studies and in
more than one species and in at least one of these studies there is
uncertainty concerning identification of the LOAEL/NOAEL for
developmental effects, the additional 10X factor for the protection of
infants and children is being retained.
E. Aggregate Risks and Determination of Safety
To assess aggregate risk, drinking water estimates were
incorporated directly into the dietary analysis, rather than using
back-calculated drinking water levels of comparison (DWLOCs). To better
evaluate aggregate risk associated with exposure through food and
drinking water, EPA is no longer comparing EDWCs generated by water
quality models with DWLOCs. Instead, EPA is now directly incorporating
the actual water quality model output concentrations into the risk
assessment. This method of incorporating water concentration into our
aggregate assessments relies on actual CSFII-reported drinking water
consumptions and more appropriately reflects the full distribution of
drinking water concentrations.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food to
prothioconazole will occupy 11% of the aPAD for females 13 years and
older, the only population subgroup of concern. In addition, there is
potential for acute dietary exposure to prothioconazole in drinking
water. The acute dietary exposure from food plus water to
prothioconazole will occupy 60% of the aPAD.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
prothioconazole from food will utilize 12% of the cPAD for the U.S.
population, 17% of the cPAD for all infants (< 1 year old), and 48% of
the cPAD for children 1-2 years old, the subpopulation at greatest
exposure. There are no residential uses for prothioconazole that result
in chronic residential exposure to prothioconazole. In addition, there
is potential for chronic dietary exposure to prothioconazole in
drinking water. The chronic dietary exposure for food plus water will
occupy 86% of the cPAD for all infants (< 1 year old). All other
population subgroups are lower.
3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level).
Prothioconazole is not registered for use on any sites that would
result in residential exposure. Therefore, the aggregate risk is the
sum of the risk from food and water, which do not exceed the Agency's
level of concern.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).
Prothioconazole is not registered for use on any sites that would
result in residential exposure. Therefore, the aggregate risk is the
sum of the risk from food and water, which do not exceed the Agency's
level of concern.
5. Aggregate cancer risk for U.S. population. The available
toxicology studies in the mouse and rat showed no increase in tumor
incidence, and therefore the Agency concluded that prothioconazole or
its metabolites are not carcinogenic, and classified ``Not Likely to be
Carcinogenic to Humans'' according to the 2005 Cancer Guidelines.
Therefore, prothioconazole is not expected to pose a cancer risk.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and to infants and children from aggregate
exposure to prothioconazole residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodologies high performance liquid
chromatography/tandem mass spectrometry (HPLC-MS/MS) and liquid
chromatography (with electrospray ionization) and tandem mass
spectrometry (LC-MS/MS)) is available to enforce the tolerance
expression. The method may be requested from: Chief, Analytical
Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft.
Meade, MD 20755-5350; telephone number: (410) 305-2905; e-mail address:
residuemethods@epa.gov.
B. International Residue Limits
There are currently no U.S., Canadian, Mexican, or international
Codex tolerances established for prothioconazole. There are no maximum
residue limits (MRLs) established for prothioconazole in Codex or in
Mexico. Maximum residue limits have been established in Canada as a
result of this Joint Review.
C. Response to Comments
A private citizen responded to PP 4F6830. Comments were received on
November 30, 2005, objecting to sale and use of this product. The
comments further stated that there are not enough long-term testing,
short-term testing is useless and unreliable and that research is not
exhaustive enough to support use.
The Agency response is as follows: The Agency considers the
database for prothioconazole to be complete and adequate for exposure
risk assessment, including several long-term studies. The commenter
submitted no scientific information to support the claims.
These comments, as well as related comments regarding animal
testing, have been responded to by the Agency on several occasions. For
example, 70 FR 1349 (January 7, 2005) (FRL-7691-4) and 69 FR 63083
(October 29, 2004) (FRL-7681-9).
V. Conclusion
Therefore, tolerances are established for combined residues of
prothioconazole, 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-
hydroxypropyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, and
prothioconazole-desthio, [alpha]-(1-chlorocyclopropyl)-[alpha]-[(2-
chlorophenyl)methyl]-1H-1,2,4-triazole-1-ethanol, calculated as parent
in or on barley, grain at 0.35 ppm; barley, hay at 7.0 ppm; barley,
straw at 4.0 ppm; grain, aspirated grain fractions at 11.0 ppm; pea and
bean, dried shelled, except soybeans, subgroup 6C at 0.9; peanut at
0.02 ppm; peanut, hay at 6.0 ppm; rapeseed, seed at 0.15 ppm; wheat,
grain at 0.07 ppm; wheat, forage at 6.0 ppm; wheat, hay at 4.5 ppm;
wheat, straw at 5.0 ppm and for combined residues of prothioconazole,
2-[2-(1-
[[Page 11783]]
chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-1,2-dihydro-3H-
1,2,4-triazole-3-thione, and prothioconazole-desthio, [alpha]-(1-
chlorocyclopropyl)-[alpha]-[(2-chlorophenyl)methyl]-1H-1,2,4-triazole-
1-ethanol, and conjugates that can be converted to these two compounds
by acid hydrolysis, calculated as parent in or on cattle, meat at 0.02
ppm; cattle, meat byproducts at 0.2 ppm; cattle, fat at 0.1 ppm; goat,
fat at 0.1 ppm; goat, meat at 0.02 ppm; goat, meat byproducts at 0.2
ppm; hog, meat byproducts at 0.05 ppm; horse, fat at 0.1 ppm, horse,
meat at 0.02 ppm; horse, meat byproducts at 0.2 ppm; milk at 0.02 ppm;
poultry, liver at 0.02 ppm; sheep, fat at 0.1 ppm; sheep, meat at 0.2
ppm and sheet, meat byproducts at 0.2 ppm.
Using upper bound residues for water derived from the proposed use
in rice, acute dietary estimates exceeded the Agency's level of concern
for food plus water. Further data is needed to resolve uncertainties
regarding residues of prothioconazole in rice application. Therefore, a
tolerance for rice is not established at this time.
Additional crop field trial data are needed to support tolerances
for black mustard, borage, flax and Indian mustard. Tolerances for
these commodities are not established at this time.
Separate tolerances are not needed for barley, pearled barley;
barley, bran; peanut, meal; wheat, bran; and wheat, germ. As per 40 CFR
180.1(h), the tolerance for rapeseed will cover the following
commodities: Canola seed, crambe seed, field mustard seed, and Indian
rapeseed.
VI. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this rule has been
exempted from review under Executive Order 12866 due to its lack of
significance, this 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 final 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 under 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 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). Since
tolerances and exemptions that are established on the basis of a
petition under section 408(d) of FFDCA, such as the tolerance in this
final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. 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 final rule directly regulates
growers, food processors, food handlers, and food retailers, not
States. This 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 FFDCA. For these same reasons, the
Agency has determined that this 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 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 rule.
VII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: March 2, 2007.
James Jones,
Director, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as ollows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. Section 180.626 is added to subpart C to read as follows:
Sec. 180.626 Prothioconazole; tolerances for residues.
(a) General. (1) Tolerances are established for combined residues
of the fungicide prothioconazole, 2-[2-(1-chlorocyclopropyl)-3-(2-
chlorophenyl)-
[[Page 11784]]
2-hydroxypropyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, and
prothioconazole-desthio, [alpha]-(1-chlorocyclopropyl)-[alpha]-[(2-
chlorophenyl)methyl]-1H-1,2,4-triazole-1-ethanol, calculated as parent
in or on the following commodities:
----------------------------------------------------------------------------------------------------------------
Commodity Parts per million
----------------------------------------------------------------------------------------------------------------
Barley, grain......................................... 0.35
Barley, hay........................................... 7.0
Barley, straw......................................... 4.0
Grain, aspirated grain fractions...................... 11
Pea and bean, dried shelled, except soybean, subgroup 0.9
6C...................................................
Peanut................................................ 0.02
Peanut, hay........................................... 6.0
Rapeseed, seed........................................ 0.15
Wheat, forage......................................... 6.0
Wheat, grain.......................................... 0.07
Wheat, hay............................................ 4.5
Wheat, straw.......................................... 5.0
----------------------------------------------------------------------------------------------------------------
(2) Tolerances are established for combined residues of the
fungicide prothioconazole, 2-[2-(1-chlorocyclopropyl)-3-(2-
chlorophenyl)-2-hydroxypropyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione,
and prothioconazole-desthio, [alpha]-(1-chlorocyclopropyl)-[alpha]-[(2-
chlorophenyl)methyl]-1H-1,2,4-triazole-1-ethanol, and conjugates that
can be converted to these two compounds by acid hydrolysis, calculated
as parent in or on the following commodities:
----------------------------------------------------------------------------------------------------------------
Commodity Parts per million
----------------------------------------------------------------------------------------------------------------
Cattle, fat........................................... 0.1
Cattle, meat.......................................... 0.02
Cattle, meat byproducts............................... 0.2
Goat, fat............................................. 0.1
Goat, meat............................................ 0.02
Goat, meat byproducts................................. 0.2
Hog, meat byproducts.................................. 0.05
Horse, fat............................................ 0.1
Horse, meat........................................... 0.02
Horse, meat byproducts................................ 0.2
Milk.................................................. 0.02
Poultry liver......................................... 0.02
Sheep, fat............................................ 0.1
Sheep, meat........................................... 0.02
Sheep, meat byproducts................................ 0.2
----------------------------------------------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. E7-4405 Filed 3-13-07; 8:45 am]
BILLING CODE 6560-50-S