[Federal Register Volume 76, Number 235 (Wednesday, December 7, 2011)]
[Rules and Regulations]
[Pages 76309-76314]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-31397]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2010-0845; FRL-8885-8]


Isoxaflutole; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
isoxaflutole in or on Soybean, seed and Grain, aspirated fractions. 
Bayer CropScience requested these tolerances under the Federal Food, 
Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective December 7, 2011. Objections and 
requests for hearings must be received on or before February 6, 2012, 
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-2010-0845. All documents in the 
docket are listed in the docket index available at http://www.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: Kathryn V. Montague, Registration 
Division (7505P), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-1243; email 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 those 
engaged in the following activities:
     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 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 get electronic access to other related information?

    You may access a frequently updated electronic version of EPA's 
tolerance regulations at 40 CFR part 180 through the Government 
Printing Office's e-CFR site at http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl. To access the 
harmonized test guidelines referenced in this document electronically, 
please go to http://www.epa.gov/ocspp and select ``Test Methods and 
Guidelines.''

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an 
objection to any aspect of this regulation and may also request a 
hearing on those

[[Page 76310]]

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-2010-0845 in the subject line on the first page of 
your submission. All objections and requests for a hearing must be in 
writing, and must be received by the Hearing Clerk on or before 
February 6, 2012. Addresses for mail and hand delivery of objections 
and hearing requests are provided in 40 CFR 178.25(b).
    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. Information not marked confidential pursuant to 40 CFR part 2 
may be disclosed publicly by EPA without prior notice. Submit a copy of 
your non-CBI objection or hearing request, identified by docket ID 
number EPA-HQ-OPP-2010-0845, 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 Facility'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. Summary of Petitioned-For Tolerance

    In the Federal Register of December 15, 2010 (75 FR 78240) (FRL-
8853-1), 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 
0F7750) by Bayer CropScience, 2 T.W. Alexander Dr., Research Triangle 
Park, NC 27709. The petition requested that 40 CFR 180.537 be amended 
by establishing tolerances for combined residues of the herbicide 
isoxaflutole, 5-cyclopropyl-4-(2-methylsulfonyl-4-
trifluoromethylbenzoyl) isoxazole and its metabolite 1-(2-
methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propane-
1,3-dione, (RPA 202248), calculated as the parent compound, in or on 
soybean at 0.05 parts per million (ppm), and soybean, aspirated grain 
fractions at 0.25 ppm. That notice referenced a summary of the petition 
prepared by Bayer CropScience, the registrant, which is available 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 and the 
preferred crop terminology, EPA has made two changes to the requested 
tolerances. First, EPA has changed the commodity descriptions for the 
tolerances to soybean, seed and grain, aspirated fractions. Second, EPA 
is raising the grain, aspirated fractions tolerance from 0.25 ppm to 
0.30 ppm.

III. Aggregate Risk Assessment and Determination of Safety

    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 * * 
*.''
    Consistent with section 408(b)(2)(D) of FFDCA, and the factors 
specified in 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 for isoxaflutole including 
exposure resulting from the tolerances established by this action. 
EPA's assessment of exposures and risks associated with isoxaflutole 
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.
    Isoxaflutole exhibited low acute toxicity via oral, dermal, and 
inhalation routes of exposure and it is not a dermal sensitizer. In 
long-term studies via the oral route, isoxaflutole caused ocular 
toxicity in rats, hepatotoxicity (including liver tumor formation) and 
thyroid tumors in rats and mice, and hematotoxicity (toxicity to blood) 
in dogs and mice at high doses. The liver and ocular toxicities 
observed in rats were consistent with the mode of action of 
isoxaflutole in mammals (i.e., inhibition of the hepatic enzyme 4-
hydroxyphenylpyruvate dioxygenase (HPPD)) that leads to a buildup of 
tyrosine in the blood and the eye.
    Developmental toxicity was observed in rats and rabbits primarily 
as growth retardations, including delays in skeletal ossification, 
effects that have been observed with other HPPD inhibitors (e.g., 
pyrasulfotole). There was no evidence of reproductive toxicity in the 
2-generation reproductive toxicity study in rats; however, both adults 
and offspring exhibited ocular and liver toxicities as seen in long-
term studies.
    In the acute and subchronic neurotoxicity studies in rats, mild 
changes in functional-observation battery (FOB) parameters (grip 
strength and/or landing foot splay) were observed in adult animals. 
However, similar effects were not observed either in pregnant animals 
or in offspring in a developmental neurotoxicity (DNT) study in rats. 
In both maternal animals and offspring, changes in body weight and/or 
food consumption were the primary effects seen in the DNT study and at 
the same dose tested. Decreased brain weights were observed in 
offspring on post-natal day (PND) 11 at the high dose only, but not at 
a later time point, an indicator of a developmental delay and/or a 
secondary effect of the decreased body weight. Although morphometric 
analyses were not performed in the study, there were no effects on pup 
swimming ability, learning, memory, motor activity, or auditory startle 
response at any dose, nor was there any evidence of neuropathology in 
the study at any dose. As a result, the missing morphometric 
measurements, while required, are unlikely to affect the tentative 
lowest-observed adverse-effect level (LOAEL) of the study (highest dose 
tested).
    Isoxaflutole was negative in a variety of genotoxicity screening 
assays. In carcinogenicity studies, isoxaflutole

[[Page 76311]]

induced liver and thyroid tumors in rats and liver tumors in mice. 
Isoxaflutole was classified as ``likely to be a human carcinogen.'' The 
method of quantification was linear cancer slope factor 
(Q1*).
    Specific information on the studies received and the nature of the 
adverse effects caused by isoxaflutole 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 in document ``Isoxaflutole. Section 3 Registration 
for Use on Soybeans. Human-Health Risk Assessment,'' p. 13 in docket ID 
number EPA-HQ-OPP-2010-0845.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern to use in evaluating the risk posed by human exposure to the 
pesticide. For hazards that have a threshold below which there is no 
appreciable risk, the toxicological POD is used as the basis for 
derivation of reference values for risk assessment. PODs are developed 
based on a careful analysis of the doses in each toxicological study to 
determine the dose at which no adverse effects are observed (the NOAEL) 
and the lowest dose at which adverse effects of concern are identified 
(the LOAEL). Uncertainty/safety factors are used in conjunction with 
the POD to calculate a safe exposure level--generally referred to as a 
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe 
margin of exposure (MOE). For non-threshold risks, the Agency assumes 
that any amount of exposure will lead to some degree of risk. Thus, the 
Agency estimates risk in terms of the probability of an occurrence of 
the adverse effect expected in a lifetime. 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/pesticides/factsheets/riskassess.htm.
    A summary of the toxicological endpoints for isoxaflutole used for 
human risk assessment is shown in the Table of this unit.

 Table 1--Summary of Toxicological Doses and Endpoints for Isoxaflutole for Use in Human Health Risk Assessment
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                                       Point of departure and
          Exposure/scenario              uncertainty/safety      RfD, PAD, LOC for risk  Study and toxicological
                                               factors                 assessment                effects
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Acute dietary (Females 13-49 years    LOAEL = 5 milligrams/     Acute RfD = aPAD = 0.02  Prenatal developmental
 of age).                              kilograms/day (mg/kg/     mg/kg/day.               toxicity (rabbit)
                                       day)                                               LOAEL = 5 mg/kg/day
                                      UFA = 10x                                           based on mg/kg/day
                                      UFH = 10x                                           based on increased
                                      FQPA SF = 3 (includes                               incidence of fetuses
                                       UFL)                                               with 27th pre-sacral
                                                                                          vertebrae.
Acute dietary (General population     NOAEL = 125 mg/kg         Acute RfD = aPAD = 1.25  Acute neurotoxicity
 including infants and children).     UFA = 10x                  mg/kg.                   (rat) LOAEL = 500 mg/
                                      UFH = 10x                                           kg based on
                                      FQPA SF = 1x                                        significant decreases
                                                                                          in hind limb grip
                                                                                          strength and landing
                                                                                          foot splay on day 15.
Chronic dietary (All populations)...  NOAEL= 2 mg/kg/day        Chronic RfD = cPAD =     Combined chronic
                                      UFA = 10x                  0.02 mg/kg/day.          toxicity/
                                      UFH = 10x                                           carcinogenicity (rat)
                                      FQPA SF = 1x                                        LOAEL = 20 mg/kg/day
                                                                                          based on liver,
                                                                                          thyroid, ocular, and
                                                                                          nervous system
                                                                                          toxicity (M) and liver
                                                                                          toxicity (F).
                                     ---------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)...  Classification: ``Likely to be Carcinogenic to Humans''. Q1* (mg/kg/day)-1
                                         of 1.14 x 10-2 from the male CD-1 mouse liver for the linear low-dose
                                          extrapolation based on statistically significant increases in liver
                                                         tumors in both sexes of mice and rats.
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UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
  of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term
  study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA
  SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD =
  reference dose. MOE = margin of exposure. LOC = level of concern.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to isoxaflutole, EPA considered exposure under the petitioned-
for tolerances as well as all existing isoxaflutole tolerances in 40 
CFR 180.537. EPA assessed dietary exposures from isoxaflutole 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.
    Such effects were identified for isoxaflutole. 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 assumed that 100% of the crop was treated and that 
for all commodities residues were at tolerance levels.
    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 assumed that 100% of 
the crop was treated and that for all commodities residues were at 
tolerance levels.
    iii. Cancer. EPA determines whether quantitative cancer exposure 
and risk assessments are appropriate for a food-use pesticide based on 
the weight of the evidence from cancer studies and other relevant data. 
If quantitative cancer risk assessment is appropriate, cancer risk may 
be quantified using a linear or nonlinear approach. If sufficient 
information on the carcinogenic mode of action is available, a 
threshold or non-linear approach is used and a cancer RfD is calculated 
based on an earlier non-cancer key event. If carcinogenic mode of 
action data are not available, or if the mode of action data

[[Page 76312]]

determines a mutagenic mode of action, a default linear cancer slope 
factor approach is utilized. Based on the data summarized in Unit 
III.A., EPA has concluded that isoxaflutole should be classified as 
``Likely to be Carcinogenic to Humans'' and a linear approach has been 
used to quantify cancer risk.
    In conducting the cancer dietary exposure assessment EPA used the 
same food consumption data from the USDA and assumptions for residue 
levels in food as the Chronic Exposure in Unit III. C. 1. ii., of this 
unit.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for isoxaflutole in drinking water. These simulation models 
take into account data on the physical, chemical, and fate/transport 
characteristics of isoxaflutole. 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 Index Reservoir Screening Tool (FIRST) and 
Screening Concentration in Ground Water (SCI-GROW) models, the 
estimated drinking water concentrations (EDWCs) of isoxaflutole and 
metabolite RPA 202248 are estimated to be 8.68 parts per billion (ppb) 
for surface water and 0.255 ppb for ground water for acute exposures, 
1.26 ppb for surface water and 0.255 ppb for ground water for chronic 
exposures for non-cancer assessments, and 0.53 ppb for surface water 
and 0.255 ppb for ground water for cancer assessments.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. For acute dietary risk 
assessment, the water concentration value of 8.68 ppb was used to 
assess the contribution to drinking water. For chronic dietary risk 
assessment, the water concentration of value 1.26 ppb was used to 
assess the contribution to drinking water. For cancer dietary risk 
assessment, the water concentration of value 0.53 ppb was used to 
assess the contribution to drinking 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). Isoxaflutole is not 
registered for any specific use patterns 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.''
    Pyrasulfotole, mesotrione, isoxaflutole, and topramezone belong to 
a class of herbicides that inhibit the liver enzyme 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, the 
ocular effect (corneal opacity) 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 
humans 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 and of itself 
cannot easily overwhelm the tyrosine-clearance mechanism in humans.
    Therefore, due to an efficient metabolic process to handle excess 
tyrosine, exposure to environmental residues of HPPD inhibiting 
herbicides is unlikely to result in high blood levels of tyrosine and 
ocular toxicity in humans; and EPA has concluded that a cumulative risk 
assessment with other HPPD inhibitors is unnecessary.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional tenfold (10X) 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. This 
additional margin of safety is commonly referred to as the FQPA Safety 
Factor (SF). In applying this provision, EPA either retains the default 
value of 10X, or uses a different additional safety factor when 
reliable data available to EPA support the choice of a different 
factor.
    2. Prenatal and postnatal sensitivity. Developmental toxicity was 
observed in rats and rabbits as growth retardations including delays in 
skeletal ossification; effects that have been observed with other HPPD 
inhibitors (e.g., pyrasulfotole). There was evidence of increased 
susceptibility in the rabbit study in the form of increased incidence 
of fetuses with 27th pre-sacral vertebrae at a dose much lower than 
those causing maternal deficits in body weight and food consumption. 
Neither the rat developmental study nor the rat 2-generation 
reproductive toxicity studies revealed any evidence of increased 
susceptibility. However, both adults and offspring in the 2-generation 
reproductive toxicity study exhibited ocular and liver toxicities seen 
in long-term studies.
    3. Conclusion. EPA has determined that reliable data show the 
safety of infants and children would be adequately protected if the 
FQPA SF were reduced to 1x for all exposure scenarios, except acute 
dietary for females 13-49 years of age for which an FQPA SF is retained 
but reduced to 3X.

[[Page 76313]]

That decision is based on the following findings:
    i. The toxicity database for isoxaflutole is complete.
    ii. There are not residual concerns regarding neurotoxicity, 
including developmental neurotoxicity, based on the results of acute, 
subchronic, and developmental neurotoxicity studies.
    iii. There is no evidence that isoxaflutole results in increased 
susceptibility following in utero exposure in a rat developmental study 
or in young rats in the 2-generation reproduction study. However, there 
was evidence of increased susceptibility following in utero exposure in 
a rabbit developmental study and a NOAEL for developmental effects was 
not identified in that study. To address the concern for increased in 
utero susceptibility and the lack of a NOAEL in the rabbit study, this 
study was selected for the acute dietary endpoint for females of 13-49 
years of age and a 3X FQPA SF was retained for that population 
subgroup. Use of a 3X FQPA SF applied to the LOAEL yielded a point of 
departure that is comparable to the point of departure for the chronic 
dietary exposure scenario and the offspring effects in the rat 2-
generation reproductive toxicity study. Therefore, all dietary exposure 
scenarios are considered protective of developmental effects.
    iv. There are no residual uncertainties identified in the exposure 
databases. EPA made the very conservative, health-protective assumption 
that all commodities for which tolerances exist or are proposed contain 
residues at the tolerance level. Additionally, EPA made conservative 
(protective) assumptions in the ground and surface water modeling used 
to assess exposure to isoxaflutole in drinking water. These assessments 
will not underestimate the exposure and risks posed by isoxaflutole.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide 
exposures are safe by comparing aggregate exposure estimates to the 
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA 
calculates the lifetime probability of acquiring cancer given the 
estimated aggregate exposure. Short-, intermediate-, and chronic-term 
risks are evaluated by comparing the estimated aggregate food, water, 
and residential exposure to the appropriate PODs to ensure that an 
adequate MOE exists.
    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food and water 
to isoxaflutole will occupy 2.4% of the aPAD for females 13 to 49 years 
old, the population group receiving the greatest exposure.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
isoxaflutole from food and water will utilize 1% of the cPAD for all 
infants (<1 year old) the population group receiving the greatest 
exposure. There are no residential uses for isoxaflutole.
    3. Short-term risk. A short-term adverse effect was identified; 
however, isoxaflutole is not registered for any use patterns that would 
result in short-term residential exposure. Short-term risk is assessed 
based on short-term residential exposure plus chronic dietary exposure. 
Because there is no short-term residential exposure and chronic dietary 
exposure has already been assessed under the appropriately protective 
cPAD (which is at least as protective as the POD used to assess short-
term risk), no further assessment of short-term risk is necessary, and 
EPA relies on the chronic dietary risk assessment for evaluating short-
term risk for isoxaflutole.
    4. Intermediate-term risk. An intermediate-term adverse effect was 
identified; however, isoxaflutole is not registered for any use 
patterns that would result in intermediate-term residential exposure. 
Intermediate-term risk is assessed based on intermediate-term 
residential exposure plus chronic dietary exposure. Because there is no 
intermediate-term residential exposure and chronic dietary exposure has 
already been assessed under the appropriately protective cPAD (which is 
at least as protective as the POD used to assess intermediate-term 
risk), no further assessment of intermediate-term risk is necessary, 
and EPA relies on the chronic dietary risk assessment for evaluating 
intermediate-term risk for isoxaflutole.
    5. Aggregate cancer risk for U.S. population. The aggregate cancer 
risk assessment for the general population takes into account exposure 
estimates from dietary consumption of isoxaflutole from food and 
drinking water sources. Average food plus water source dietary exposure 
was used. Estimated cancer risk for the U.S. population includes 
infants and children. The aggregate cancer risk estimate for 
isoxaflutole is 8 x 10-7. This risk estimate is based, in 
part, on the conservative assumption that 100% of all crops for which 
isoxaflutole is registered or proposed for registration are treated. 
Additional refinement using percent crop treated estimates would result 
in a lower estimate of cancer risk.
    EPA generally considers cancer risks in the range of one in one 
million (1 x 10-6) or less to be negligible. Accordingly, 
EPA has concluded the cancer risk for all existing isoxaflutole uses 
and the uses associated with the tolerances established in this action 
is negligible.
    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 isoxaflutole residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (liquid chromatography with tandem 
mass spectrometry (LC/MS/MS) method (IS-004-P10-02)) 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; email address: 
[email protected].

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and 
Agriculture Organization/World Health Organization food standards 
program, and it is recognized as an international food safety 
standards-setting organization in trade agreements to which the United 
States is a party. EPA may establish a tolerance that is different from 
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level.
    The Codex has not established a MRL for isoxaflutole.

V. Conclusion

    Therefore, tolerances are established for residues of isoxaflutole, 
(5-cyclopropyl-4-isoxazolyl) [2-(methylsulfonyl)-4-
(trifluoromethyl)phenyl] methanone and its metabolite 1-(2-
methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propane-
1,3-dione, in or on

[[Page 76314]]

soybean, seed and grain, aspirated fractions at 0.05 ppm and 0.30 ppm, 
respectively.

VI. Statutory and Executive Order Reviews

    This final rule establishes tolerances 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 final rule has been 
exempted from review under Executive Order 12866, this final rule is 
not subject to Executive Order 13211, entitled 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.
    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 9, 2000) do not apply to this final rule. In addition, 
this final 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) (Pub. L. 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: November 21, 2011.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I 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 180.537 is amended in paragraph (a) by revising the 
introductory text and alphabetically adding the following commodities 
to the table to read as follows:


Sec.  180.537  Isoxaflutole; tolerances for residues.

    (a) General. Tolerances are established for residues of the 
herbicide, isoxaflutole, including its metabolites and degradates, in 
or on the commodities in the table below. Compliance with the tolerance 
levels specified below is to be determined by measuring only the sum of 
isoxaflutole ((5-cyclopropyl-4-isoxazolyl) [2-(methylsulfonyl)-4-
(trifluoromethyl)phenyl] methanone) and its metabolite 1-(2-
methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propan-
1,3-dione (RPA 202248), calculated as the stoichiometric equivalent of 
isoxaflutole, in or on the commodity:

------------------------------------------------------------------------
                                                               Parts per
                          Commodity                             million
------------------------------------------------------------------------
 
                                * * * * *
Grain, aspirated fractions..................................        0.30
Soybean, seed...............................................        0.05
------------------------------------------------------------------------

* * * * *
[FR Doc. 2011-31397 Filed 12-6-11; 8:45 am]
BILLING CODE 6560-50-P