[Federal Register Volume 76, Number 235 (Wednesday, December 7, 2011)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-31397]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Isoxaflutole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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)
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:
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
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
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
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
trifluoromethylbenzoyl) isoxazole and its metabolite 1-(2-
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
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
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
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-
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
Isoxaflutole was negative in a variety of genotoxicity screening
assays. In carcinogenicity studies, isoxaflutole
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
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
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
Point of departure and
Exposure/scenario uncertainty/safety RfD, PAD, LOC for risk Study and toxicological
factors assessment effects
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
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
toxicity (M) and liver
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.
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
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
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
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
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
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
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.
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
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:
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.
Therefore, tolerances are established for residues of isoxaflutole,
(trifluoromethyl)phenyl] methanone and its metabolite 1-(2-
1,3-dione, in or on
soybean, seed and grain, aspirated fractions at 0.05 ppm and 0.30 ppm,
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
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
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: November 21, 2011.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.537 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-
1,3-dione (RPA 202248), calculated as the stoichiometric equivalent of
isoxaflutole, in or on the commodity:
* * * * *
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