[Federal Register: August 15, 2007 (Volume 72, Number 157)]
[Rules and Regulations]
[Page 45643-45649]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15au07-14]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2006-1026; FRL-8141-8]
Pyrasulfotole; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a tolerance for residues of
pyrasulfotole in or on small cereal grains, including barley, oats,
rye, triticale, and wheat; as well as livestock commodities. Bayer
CropScience requested this tolerance under the Federal Food, Drug, and
Cosmetic Act (FFDCA).
DATES: This regulation is effective August 15, 2007. Objections and
requests for hearings must be received on or before October 15, 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-2006-1026. 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 web site to view the docket index or access
available documents. All documents in the docket are listed in the
docket index available in regulations.gov. Although listed in the
index, some information is not publicly available, e.g., Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available in the electronic docket at http://www.regulations.gov, or,
if only available in hard copy, at the OPP Regulatory Public Docket in
Rm. S-4400, One Potomac Yard (South Building), 2777 S. Crystal Drive,
Arlington, VA. The Docket Facility is open 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: Joanne I. Miller, Registration
Division (7505P), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-6224; e-mail address:
miller.joanne@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 those
engaged in the following activities:
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 to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at http://www.regulations.gov
, you may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of EPA's tolerance regulations at
40 CFR part 180 through the Government Printing Office's pilot e-CFR
site at http://www.gpoaccess.gov/ecfr.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of the FFDCA, any person may file an objection
to any aspect of this regulation and may also
[[Page 45644]]
request a hearing on those objections. 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-2006-1026 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 as
required by 40 CFR part 178 on or before October 15, 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 this copy, identified by docket ID number
EPA-HQ-OPP-2006-1026, 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.
II. Petition for Tolerance
In the Federal Register of February 7, 2007 (72 FR 5706) (FRL-8111-
8), 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
6F7059) by Bayer CropScience, 2 T.W. Alexander Drive, Research Triangle
Park, NC 27709. The petition requested that 40 CFR 180.631 be amended
by establishing a tolerance for residues of the herbicide pyrasulfotole
(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-
(trifluoromethyl)phenyl]methanone, and its metabolite, 5-hydroxy-3-
methyl-1H-pyrazol-4-yl) [2-methylsulfornyl)-4-
(trifluoromethyl)phenyl]methanone, in or on barley, oat, rye,
triticale, wheat, grain at 0.07 parts per million (ppm), barley, oat,
rye, wheat, straw and oat, rye, wheat, forage at 0.25 ppm, barley, oat,
wheat, hay at 0.8 ppm, wheat, aspirated grain fractions at 1.4 ppm. In
addition, Bayer CropScience has requested permanent tolerances for
pyrsulfotole per se for cattle, goat, hog, horse, sheep, meat and fat
at 0.01 ppm, cattle, goat, hog, horse, sheep, meat byproducts at 0.3
ppm, and milk at 0.005 ppm. That notice referenced a summary of the
petition prepared by Bayer CropScience, the registrant, which is
available to the public in the docket, http://www.regulations.gov.
There were no comments received in response to the notice of filing.
Based upon review of the data supporting the petition, EPA has
modified the tolerance levels as follows: aspirated grain fractions at
0.40 ppm, barley, grain at 0.02 ppm, barley, hay at 0.30 ppm, barley,
straw at 0.20 ppm, cattle, fat at 0.02 ppm, cattle, liver at 0.35 ppm,
cattle, meat at 0.02 ppm, cattle, meat byproducts, except liver at 0.06
ppm, eggs at 0.02 ppm, goat, fat at 0.02 ppm, goat meat at 0.02 ppm,
goat, meat byproducts, except liver at 0.06 ppm, hog, fat at 0.02 ppm,
hog, meat at 0.02 ppm, hog, meat byproducts at 0.02 ppm, horse, fat at
0.02 ppm, horse, liver at 0.35 ppm, horse, meat at 0.02 ppm, horse,
meat byproducts, except liver at 0.06 ppm, milk at 0.01 ppm, oat,
forage at 0.10 ppm, oat, grain at 0.08 ppm, oat, hay at 0.50 ppm, oat,
straw at 0.20 ppm, poultry, fat at 0.02 ppm, poultry, meat at 0.02 ppm,
poultry, meat byproducts at 0.02 ppm, rye, forage at 0.20 ppm, rye,
grain at 0.02 ppm, rye, straw at 0.20 ppm, sheep, fat at 0.02 ppm,
sheep, liver at 0.35 ppm, sheep, meat at 0.02 ppm, sheep, meat
byproducts, except liver at 0.06 ppm, wheat, forage at 0.20 ppm, wheat,
grain at 0.02 ppm, wheat, hay at 0.80 ppm, and wheat, straw at 0.20
ppm.
III. Aggregate Risk Assessment and Determination of Safety
Section 408(b)(2)(A)(i) of the 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 the FFDCA defines ``safe'' to mean that ``there is
a reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of the 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....'' These provisions were added to the FFDCA by the Food
Quality Protection Act (FQPA) of 1996.
Consistent with FFDCA section 408(b)(2)(D), and the factors
specified in section 408(b)(2)(D), 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 for the petitioned-for tolerance
for residues of pyrasulfotole and pyrasulfotole-desmethyl on aspirated
grain fractions at 0.40 ppm, barley, grain at 0.02 ppm, barley, hay at
0.30 ppm, barley, straw at 0.20 ppm, cattle, fat at 0.02 ppm, cattle,
liver at 0.35 ppm, cattle, meat at 0.02 ppm, cattle, meat byproducts,
except liver at 0.06 ppm, eggs at 0.02 ppm, goat, fat at 0.02 ppm, goat
meat at 0.02 ppm, goat, meat byproducts, except liver at 0.06 ppm, hog,
fat at 0.02 ppm, hog, meat at 0.02 ppm, hog, meat byproducts at 0.02
ppm, horse, fat at 0.02 ppm, horse, liver at 0.35 ppm, horse, meat at
0.02 ppm, horse, meat byproducts, except liver at 0.06 ppm, milk at
0.01 ppm, oat, forage at 0.10 ppm, oat, grain at 0.08 ppm, oat, hay at
0.50 ppm, oat, straw at 0.20 ppm, poultry, fat at 0.02 ppm, poultry,
meat at 0.02 ppm, poultry, meat byproducts at 0.02 ppm, rye, forage at
0.20 ppm, rye, grain at 0.02 ppm, rye, straw at 0.20 ppm, sheep, fat at
0.02 ppm, sheep, liver at 0.35 ppm, sheep, meat at 0.02 ppm, sheep,
meat byproducts, except liver at 0.06 ppm, wheat, forage at 0.20 ppm,
wheat, grain at 0.02 ppm, wheat, hay at 0.80 ppm, and wheat, straw at
0.20 ppm. EPA's assessment of exposures and risks associated with
establishing the tolerance follows.
For pyrasulfotole, aggregate exposure risk assessments were
performed for the following scenarios: Acute aggregate exposure (food
and drinking water), and chronic aggregate exposure (food and drinking
water). Short- and intermediate-term assessments, which are used to
evaluate aggregate dietary and residential exposures, were not
performed because there are no registered or proposed residential non-
food uses. Although pyrasulfotole is classified as ``Suggestive
Evidence of Carcinogenicity,'' EPA determined that separate
quantifications of cancer risks is not required noting that the
progression of non-neoplastic related lesions in both the rats and mice
was biologically plausible by non-genotoxic
[[Page 45645]]
modes of action for both the corneal tumors and the bladder tumors.
Therefore, the chronic RfD will be protective of cancer and non-cancer
effects.
Pyrasulfotole belongs to a class of herbicides that inhibit the
liver enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), which is
involved in the catabolism (metabolic breakdown) of tyrosine (an amino
acid derived from proteins in the diet). Inhibition of HPPD can result
in elevated tyrosine levels in the blood, a condition called
tyrosinemia. HPPD-inhibiting herbicides have been found to cause a
number of toxicities in laboratory animal studies including ocular,
developmental, liver, and kidney effects. Of these toxicities, it is
the ocular effect (corneal opacity) that is highly correlated with the
elevated blood tyrosine levels. In fact, rats dosed with tyrosine alone
show ocular opacities similar to those seen with HPPD inhibitors.
Although the other toxicities may be associated with chemically-induced
tyrosinemia, other mechanisms may also be involved.
There are marked differences among species in the ocular toxicity
associated with inhibition of HPPD. Ocular effects following treatment
with HPPD inhibitor herbicides are seen in the rat but not in the
mouse. Monkeys also seem to be recalcitrant to the ocular toxicity
induced by HPPD inhibition. The explanation of this species-specific
response in ocular opacity is related to the species differences in the
clearance of tyrosine. A metabolic pathway exists to remove tyrosine
from the blood that involves a liver enzyme called tyrosine
aminotransferase (TAT). In contrast to rats where ocular toxicity is
observed following exposure to HPPD-inhibiting herbicides, mice and
human are unlikely to achieve the levels of plasma tyrosine necessary
to produce ocular opacities because the activity of TAT in these
species is much greater compared to rats. Thus, humans and mice have a
highly effective metabolic process for handling excess tyrosine.
HPPD inhibitors (e.g., Nitisinone) are used as an effective
therapeutic agent to treat patients suffering from rare genetic
diseases of tyrosine catabolism. Treatment starts in childhood but is
often sustained throughout patient's lifetime. The human experience
indicates that a therapeutic dose (1 mg/kg/day dose) of Nitisinone has
an excellent safety record in infants, children, and adults and that
serious adverse health outcomes have not been observed in a population
followed for approximately a decade. Rarely, ocular effects are seen in
patients with high plasma tyrosine levels; however these effects are
transient and can be readily reversed upon adherence to a restricted
protein diet. This indicates that an HPPD inhibitor in it of itself
cannot easily overwhelm the tyrosine-clearance mechanism in humans.
Therefore, exposure to environmental residues of HPPD-inhibiting
herbicides are unlikely to result in the high blood levels of tyrosine
and ocular toxicity in humans due to an efficient metabolic process to
handle excess tyrosine. Nonetheless, because EPA has not yet developed
an alternate risk assessment endpoint, model, or cross-species
extrapolation method for pyrasulfotole, EPA has assessed chronic risk
from exposure to pyrasulfotole based on its ocular effects in rats. Due
to the limited relevance to humans of this endpoint, this approach to
assessing chronic risk for pyrasulfotole must be regarded as worst
case. In the future, assessment of HPPD-inhibiting herbicides will
consider more appropriate models and cross species extrapolation
methods.
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 adverse effects caused by pyrasulfotole 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.
The referenced document, entitled ``Pyrasulfotole:
Human Health Risk Assessment for Proposed Uses on Small Cereal
Grains,'' is available in the docket established by this action, (EPA-
HQ-OPP-2006-1026).
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, the toxicological level of concern (LOC) is derived
from the highest dose at which no adverse effects are observed (the
NOAEL) in the toxicology study identified as appropriate for use in
risk assessment. However, if a NOAEL cannot be determined, the lowest
dose at which adverse effects of concern are identified (the LOAEL) is
sometimes used for risk assessment. Uncertainty/safety factors (UF) are
used in conjunction with the LOC to take into account 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. Safety is assessed for acute and chronic
risks by comparing aggregate exposure to the pesticide to the acute
population adjusted dose (aPAD) and chronic population adjusted dose
(cPAD). The aPAD and cPAD are calculated by dividing the LOC by all
applicable uncertainty/safety factors. Short-, intermediate, and long-
term risks are evaluated by comparing aggregate exposure to the LOC to
ensure that the margin of exposure (MOE) called for by the product of
all applicable uncertainty/safety factors is not exceeded.
For non-threshold risks, the Agency assumes that any amount of
exposure will lead to some degree of risk and estimates risk in terms
of the probability of occurrence of additional adverse cases.
Generally, cancer risks are considered non-threshold. For more
information on the general principles EPA uses in risk characterization
and a complete description of the risk assessment process, see http://www.epa.gov/fedrgstr/EPA-PEST/1997/November/Day-26/p30948.htm
.
A summary of the toxicological endpoints for pyrasulfotole used for
human risk assessment is shown in Table 1. of this unit.
[[Page 45646]]
Table 1.--Summary of Toxicological Dose and Endpoints for Pyrasulfotole for Use in Human Risk Assessment
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Dose Used in Risk Uncertainty/FQPA Safety Study and Toxicological
Exposure/Scenario Assessment Factors\1\ Effects
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Acute Dietary (All populations) NOAEL = 3.8 mg/kg/day UFA = 10X Developmental
UFH = 10X.............. neurotoxicity (rat;
UFFQPA = 1X............ dietary) offspring
LOAEL = 37 mg/kg/day
based on delayed
preputial separation
(males), decreased
cerebrum length (PND
21 females), and
decreased cerebellum
height (PND 21 males)
----------------------------------------------------------------------------------------------------------------
Chronic Dietary (All populations) NOAEL= 1.0 mg/kg/day UFA = 10X Combined chronic
UFH = 10X.............. toxicity/
UFFQPA = 1X............ carcinogenicity (rat;
dietary)
LOAEL = 10/14 mg/kg/day
(M/F) based on corneal
opacity,
neovascularization of
the cornea,
inflammation of the
cornea, regenerative
corneal hyperplasia,
corneal atrophy, and /
or retinal atrophy
(both sexes), and
hepatocellar
hypertrophy along with
increased serum
cholesterol (males)
----------------------------------------------------------------------------------------------------------------
Incidental Oral Short-and NOAEL= 2.5 mg/kg/day UFA = 10X Reproduction and
Intermediate-Term (1-30 days and 1-6 UFH = 10X.............. fertility effects
months) UFFQPA = 1X............ (rat; dietary)
offspring
LOAEL = 26.3/32.6 mg/kg
bw/day (M/F) based on
corneal opacity and/or
corneal
neovascularization (F1
and F2 generations)
----------------------------------------------------------------------------------------------------------------
Dermal Short- and Intermediate-Term NOAEL = 10 mg/kg/day UFA = 10X 28-day dermal toxicity
(1-30 days and 1-6 months) UFH = 10X.............. (rat)
LOAEL = 100 mg/kg bw/
day (M/F) based on
focal degeneration of
pancreas (both sexes)
and alteration of
thyroid colloid
(males)
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Dermal Long-Term (> 6 months) NOAEL= 1.0 mg/kg/day UFA = 10X Combined chronic
Estimated dermal UFH = 10X.............. toxicity/
absorption factor = carcinogenicity (rat;
2.5%. dietary)
LOAEL = 10/14 mg/kg/day
(M/F) based on corneal
opacity,
neovascularization of
the cornea,
inflammation of the
cornea, regenerative
corneal hyperplasia,
corneal atrophy, and/
or retinal atrophy
(both sexes), and
hepatocellular
hypertrophy along with
increased serum
cholesterol (males)
----------------------------------------------------------------------------------------------------------------
Inhalation (All durations) NOAEL = 1.0 mg/kg/day UFA = 10X Combined chronic
100% inhalation asumed. UFH = 10X.............. toxicity/
carcinogenicity (rat;
dietary)
LOAEL = 10/14 mg/kg/day
(M/F) based on corneal
opacity,
neovascularization of
the cornea,
inflammation of the
cornea, regenerative
corneal hyperplasia,
corneal atrophy, and/
or retinal atrophy
(both sexes), and
hepatocellular
hypertrophy along with
increased serum
cholesterol (males)
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation) Classification: ``Suggestive Evidence of Carcinogenic Potential'' based
on increased incidences of corneal tumors in male rats (oral
carcinogenicity study) and urinary bladder tumors in male and female
mice (oral carcinogenicity study)
----------------------------------------------------------------------------------------------------------------
\1\UF = Uncertainty factor, UFA = Extrapolation from animal to human (interspecies), UFH = Potential variation
in sensitivity among members of the human population (intraspecies), and UFFQPA = Food Quality Protection Act
(FQPA) safety factor.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to pyrasulfotole, EPA assessed dietary exposures from
pyrasulfotole 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 one-day or single exposure. In estimating acute
dietary exposure, EPA used food consumption information from the United
States Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide
Continuing Surveys of Food Intake by Individuals (CSFII). As to residue
levels in food, EPA relied upon tolerance-level residues and assuming
100% crop treated information for all commodities.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA 1994-1996
and 1998 CSFII. As to residue levels in food, EPA relied upon
tolerance-level residues and assuming 100% crop treated information for
all commodities.
iii. Cancer. Pyrasulfotole has been classified by the EPA as having
``Suggestive Evidence of Carcinogenic Potential,'' based on increased
incidences of corneal tumors in male rats at the highest dose tested
(2,500 ppm) in the chronic toxicity/
[[Page 45647]]
carcinogenicity study in rat and urinary bladder transitional cell
tumors in male and female mice at the highest dose tested (4,000 ppm)
in the mouse carcinogenicity study. These tumors were observed at doses
that were considered excessive due to increased mortality caused by
urinary bladder stones. EPA noted that the progression of non-
neoplastic related lesions in both the rats and mice was biologically
plausible by non-genotoxic modes of action for both the corneal tumors
and the bladder tumors. Therefore, the chronic RfD of 0.01 mg/kg/day,
based on the rat chronic toxicity/carcinogenicity study (NOAEL= 25 ppm
(1 mg/kg/day) and LOAEL of 250 ppm (10 mg/kg/day)) would be protective
of both non-cancer and potential cancer precursor effects.
Quantifications of separate cancer risk was not required.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring data to complete a comprehensive dietary exposure
analysis and risk assessment for pyrasulfotole 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 environmental
fate characteristics of pyrasulfotole. 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 FIRST and SCI-GROW models, the estimated drinking
water environmental concentrations (EDWCs) of pyrasulfotole for acute
exposures are estimated to be 4.0 parts per billion (ppb) for surface
water and 1.4 ppb for ground water. The EECs for chronic exposures are
estimated to be 2.8 ppb for surface water and 1.4 ppb for ground water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For acute dietary risk
assessment, the water concentration value of 4.0 ppb was used to access
the contribution to drinking water. For chronic dietary risk
assessment, the water concentration of value 2.8 ppb was used to access
the contribution to drinking water.
The pyrasulfotole risk assessment team determined that the residue
of concern in drinking water for risk assessment purposes is parent
only. Pyrasulfotole-benzoic acid was identified as the only
environmental degradate in the soil metabolism and terrestrial field
dissipation studies. Based on available toxicology studies on
pyrasulfotole-benzoic acid, EPA determined that it is not of
toxicological concern, and thus, should not be included in the drinking
water assessment for pyrasulfotole.
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). Pyrasulfotole is not
proposed or 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 the 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.''
Pyrasulfotole belongs to a class of herbicides (including
mesotrione, isoxaflutole, and topramezone) that inhibit the liver
enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD). EPA has concluded
that the ocular effects caused by these herbicides has limited
relevance to humans. In the future, assessments of HPPD-inhibiting
herbicides will consider more appropriate models and cross species
extrapolation methods.
For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative
.
D. Safety Factor for Infants and Children
1. In general. Section 408 of FFDCA provides that EPA shall apply
an additional (10X) 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 based on reliable data that a different margin of
safety will be safe for infants and children. This additional margin of
safety is commonly referred to as the FQPA safety factor. 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 FQPA
safety factor value based on the use of traditional uncertainty/safety
factors and/or special FQPA safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. Increased quantitative
susceptibility of offspring was observed in the rabbit developmental
toxicity study, since offspring toxicity (skeletal anomalies/
variations) was observed at a lower dose than maternal toxicity
(decreased body weight gain, food consumption). No evidence of
quantitative susceptibility following in utero and/or postnatal
exposure was observed in the prenatal developmental toxicity study in
rats, the developmental neurotoxicity (DNT) study in rats, or in the 2-
generation rat reproductive toxicity study. Offspring toxicity
(skeletal variations; decreased body weight (males)) was observed at
the same dose as maternal toxicity (clinical signs, decreased body
weight, enlarged placenta) in the prenatal developmental toxicity study
in rats. Offspring toxicity (e.g., ocular toxicity, effects on
learning/memory, effects on brain morphometry) was also observed at the
same dose as maternal toxicity (ocular opacity) in the DNT study. Last,
offspring toxicity (ocular toxicity) was observed at the same as or
higher doses than parental toxicity (thyroid effects) in the 2-
generation rat reproductive toxicity study.
3. Conclusion. EPA has determined that reliable data show that it
would be safe for infants and children to reduce the FQPA safety factor
to 1X. That decision is based on the following findings:
i. The toxicology database is complete.
ii. There are no residual uncertainties concerning pre- and
postnatal toxicity. Clear NOAELs were established for all exposure
scenarios and these are considered protective of the offspring
susceptibility observed in the rabbit developmental toxicity study. The
concern for increased susceptibility seen in rabbit developmental
toxicity study is low because a) there is well established
developmental NOAEL in the rabbit developmental toxicity study in
rabbits protecting fetuses from skeletal anomalies/variations, b) the
increased succeptibility was not seen in rat developmental toxicity
study, developmental neurotoxicity study in rats and two generation
reproduction study in rats, c) the NOAEL of the study chosen for the
chronic RfD is 10x lower than the rabbit developmental toxicity study
NOAEL (10 mg/kg/day).
iii. There are no registered or proposed uses of pyrasulfotole
which would result in residential exposure.
iv. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed based
on 100% crop treated and tolerance-level residues for
[[Page 45648]]
all proposed commodities. By using this screening-level assessment, the
acute and chronic exposures/risks will not be underestimated. The
dietary drinking water assessment (unrefined estimates) utilizes values
generated by model and associated modeling parameters which are
designed to provide conservative, health protective, high-end estimates
of water concentrations.
E. Aggregate Risks and Determination of Safety
Safety is assessed for acute and chronic risks by comparing
aggregate exposure to the pesticide to the acute population adjusted
dose (aPAD) and chronic population adjusted dose (cPAD). The aPAD and
cPAD are calculated by dividing the LOC by all applicable uncertainty/
safety factors. For linear cancer risks, EPA calculates the probability
of additional cancer cases given aggregate exposure. Short-,
intermediate, and long-term risks are evaluated by comparing aggregate
exposure to the LOC to ensure that the margin of exposure (MOE) called
for by the product of all applicable uncertainty/safety factors is not
exceeded.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food and water
to pyrasulfotole and pyrasulfotole-desmethyl will occupy 2% of the aPAD
for the general U.S. population and at 4% of the aPAD for children 1-2
years old, the most highly exposed population subgroup.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
pyrasulfotole and pyrasulfotole-desmethyl from food and water will
utilize 2% of the cPAD for the general U.S. population and at 7% of the
cPAD for children 1-2 years old, the most highly exposed population
subgroup.
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). Pyrasulfotole 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.
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). Pyrasulfotole
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. Pyrasulfotole has
been classified by EPA as having ``Suggestive Evidence of Carcinogenic
Potential,'' based on increased incidences of corneal tumors in male
rats at the highest dose tested (2,500 ppm) in the chronic toxicity/
carcinogenicity study in rat and urinary bladder transitional cell
tumors in male and female mice at the highest dose tested (4,000 ppm)
in the mouse carcinogenicity study. The chronic RfD of 0.01 mg/kg/day,
based on the rat chronic toxicity/carcinogenicity study (NOAEL = 25 ppm
(1 mg/kg/day) and LOAEL of 250 ppm (10 mg/kg/day)) would be protective
of both non-cancer and cancer effects.
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, or to infants and children from aggregate
exposure to pyrasulfotole and pyrasulfotole-desmethyl residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology high-performance liquid
chromatography (HPLC)/mass spectrometry (MS)/MS method (Method AI-004-
A05-01) 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 no established Mexican, Canadian, or Codex MRLs for the
proposed uses. Pyrasulfotole was evaluated as part of a trilateral
joint review with Canada and Australia. All EPA-recommended tolerances
are the same as those being established in Canada and Australia.
Therefore, harmonization is not an issue at this time.
V. Conclusion
Therefore, the tolerance is established for residues of
pyrasulfotole and pyrasulfotole-desmethyl, (5-hydroxy-1,3-dimethyl-1H-
pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluoromethyl)phenyl]methanone,
and its metabolite, 5-hydroxy-3-methyl-1H-pyrazol-4-yl) [2-
methylsulfornyl)-4-(trifluoromethyl)phenyl]methanone, in or on
aspirated grain fractions at 0.40 ppm, barley, grain at 0.02 ppm,
barley, hay at 0.30 ppm, barley, straw at 0.20 ppm, cattle, fat at 0.02
ppm, cattle, liver at 0.35 ppm, cattle, meat at 0.02 ppm, cattle, meat
byproducts, except liver at 0.06 ppm, eggs at 0.02 ppm, goat, fat at
0.02 ppm, goat meat at 0.02 ppm, goat, meat byproducts, except liver at
0.06 ppm, hog, fat at 0.02 ppm, hog, meat at 0.02 ppm, hog, meat
byproducts at 0.02 ppm, horse, fat at 0.02 ppm, horse, liver at 0.35
ppm, horse, meat at 0.02 ppm, horse, meat byproducts, except liver at
0.06 ppm, milk at 0.01 ppm, oat, forage at 0.10 ppm, oat, grain at 0.08
ppm, oat, hay at 0.50 ppm, oat, straw at 0.20 ppm, poultry, fat at 0.02
ppm, poultry, meat at 0.02 ppm, poultry, meat byproducts at 0.02 ppm,
rye, forage at 0.20 ppm, rye, grain at 0.02 ppm, rye, straw at 0.20
ppm, sheep, fat at 0.02 ppm, sheep, liver at 0.35 ppm, sheep, meat at
0.02 ppm, sheep, meat byproducts, except liver at 0.06 ppm, wheat,
forage at 0.20 ppm, wheat, grain at 0.02 ppm, wheat, hay at 0.80 ppm,
and wheat, straw at 0.20 ppm.
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, 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) or Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997). 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., 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).
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.
[[Page 45649]]
This final rule directly regulates growers, food processors, food
handlers and food retailers, not States or tribes, nor does this action
alter the relationships or distribution of power and responsibilities
established by Congress in the preemption provisions of section
408(n)(4) of FFDCA. As such, the Agency has determined that this action
will not have a substantial direct effect on States or tribal
governments, on the relationship between the national government and
the States or tribal governments, or on the distribution of power and
responsibilities among the various levels of government or between the
Federal Government and Indian tribes. Thus, the Agency has determined
that Executive Order 13132, entitled Federalism (64 FR 43255, August
10, 1999) and Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (65 FR 67249, November 6,
2000) do not apply to this rule. In addition, This rule does not 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).
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).
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: August 1, 2007.
Debra Edwards,
Director, Office of Pesticide Programs.
0
Therefore, 40 CFR part 180 is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. Section 180.631 is added to read as follows:
Sec. 180.631 Pyrasulfotole; tolerances for residues.
(a) General. Tolerances are established for residues of the
herbicide pyrasulfotole and pyrasulfotole-desmethyl, (5-hydroxy-1,3-
dimethyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-
(trifluoromethyl)phenyl]methanone, and its metabolite, 5-hydroxy-3-
methyl-1H-pyrazol-4-yl) [2-methylsulfornyl)-4-
(trifluoromethyl)phenyl]methanone, in or on the following agricultural
commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Aspirated grain fractions.................................. 0.40
Barley, grain.............................................. 0.02
Barley, hay................................................ 0.30
Barley, straw.............................................. 0.20
Cattle, fat................................................ 0.02
Cattle, liver.............................................. 0.35
Cattle, meat............................................... 0.02
Cattle, meat byproducts, except liver...................... 0.06
Eggs....................................................... 0.02
Goat, fat.................................................. 0.02
Goat, liver................................................ 0.35
Goat, meat................................................. 0.02
Goat, meat byproducts, except liver........................ 0.06
Hog, fat................................................... 0.02
Hog, meat.................................................. 0.02
Hog, meat byproducts....................................... 0.02
Horse, fat................................................. 0.02
Horse, liver............................................... 0.35
Horse, meat................................................ 0.02
Horse, meat byproducts, except liver....................... 0.06
Milk....................................................... 0.01
Oat, forage................................................ 0.10
Oat, grain................................................. 0.08
Oat, hay................................................... 0.50
Oat, straw................................................. 0.20
Poultry, fat............................................... 0.02
Poultry, meat.............................................. 0.02
Poultry, meat byproducts................................... 0.02
Rye, forage................................................ 0.20
Rye, grain................................................. 0.02
Rye, straw................................................. 0.20
Sheep, fat................................................. 0.02
Sheep, liver............................................... 0.35
Sheep, meat................................................ 0.02
Sheep, meat byproducts, except liver....................... 0.06
Wheat, forage.............................................. 0.20
Wheat, grain............................................... 0.02
Wheat, hay................................................. 0.80
Wheat, straw............................................... 0.20
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. E7-15698 Filed 8-14-07; 8:45 am]
BILLING CODE 6560-50-S