[Federal Register Volume 75, Number 218 (Friday, November 12, 2010)]
[Rules and Regulations]
[Pages 69353-69360]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-28499]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2007-0504; FRL-8845-6]
Isoxaben; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of
isoxaben in or on almond, hulls; grape; nut, tree, group 14; and
pistachio. Dow AgroSciences requested these tolerances under the
Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective November 12, 2010. Objections and
requests for hearings must be received on or before January 11, 2011,
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-2007-0504. 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-
[[Page 69354]]
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: Susan Stanton, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-5218; e-mail address: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this action apply to me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to 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://www.gpoaccess.gov/ecfr. 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 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-2007-0504 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
January 11, 2011. 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-2007-0504, 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 August 1, 2007 (72 FR 42072) (FRL-8138-
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
7F7222) by Dow AgroSciences, 9330 Zionsville Road, Indianapolis, IN
46268. The petition requested that 40 CFR part 180 be amended by adding
a section for the herbicide, isoxaben, and establishing tolerances
therein for residues of isoxaben, N-[3-(1-ethyl-1-methylpropyl)-5-
isoxazolyl]-2, 6-dimethoxybenzamide, in or on almond, hulls at 0.35
parts per million (ppm); grape; grape, juice; and grape, raisin at 0.01
ppm; and nut, tree, group 14 and pistachio at 0.03 ppm. That notice
referenced a summary of the petition prepared by Dow AgroSciences, 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, EPA has
reduced the tolerances for nut, tree, group 14 and pistachio from 0.03
ppm to 0.02 ppm and increased the tolerance for almond, hulls from 0.35
ppm to 0.40 ppm. EPA has also determined that the proposed tolerances
for grape, juice and grape, raisin are not needed. Finally, EPA has
revised the requested tolerance expression in accordance with current
policy. The reasons for these changes are explained in Unit IV.C.
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 isoxaben including
exposure resulting from the tolerances established by this action.
EPA's assessment of exposures and risks associated with isoxaben
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
[[Page 69355]]
concerning the variability of the sensitivities of major identifiable
subgroups of consumers, including infants and children.
Isoxaben is of low acute toxicity when administered orally,
dermally, or via inhalation. It is not a dermal sensitizer or skin
irritant and causes only minor transient irritation to the eye.
The primary target organs identified for isoxaben in repeated-dose
studies are the liver and kidney. Although liver effects were observed
in all species tested (rat, dog, mouse), adverse changes were only
observed in the mouse following chronic oral exposure. These effects
included histopathology and increased blood alkaline phosphatase and
alanine aminotransferase activities at high doses. In the dog and rat,
liver effects were considered adaptive and consisted of enlargement,
hepatocellular hypertrophy and induction of hepatic microsomal enzymes.
Increased incidence and severity of nephropathy was observed in the rat
following chronic (2-year) exposure. No adverse renal effects were
reported in the dog or mouse. There was no indication of neurotoxicity
or immunotoxicity in the available studies, which generally tested up
to or above the limit dose.
No maternal or developmental effects were seen in the rabbit or rat
developmental studies. In the rat reproductive toxicity study, two
matings (a and b generations) per F0 and F1 parental generations were
conducted, plus two additional matings (F2c and
F3a) to examine developmental effects on gestation day 20.
Effects included a decrease in corpora lutea, resulting in a decrease
in the mean number of implantations and mean live fetuses per litter.
Nursing pups showed decreased body weight gain at the highest dose
tested. An increase in the incidence of several malformations
(exencephaly, microphthalmia/coloboma and hydroureter) was seen in the
F2b, F2c and F3a mating generations at
the limit dose of 1,000 milligrams/kilogram/day (mg/kg/day highest dose
tested (HDT)), but not in the F1a, F1b or
F2a offspring. The relationship of these findings to
treatment is unclear because an examination of the genealogy of these
offspring suggests a possible heritable component. A large percentage
of the affected litters were the result of either cousin matings or had
in common F0 progenitors derived from several F0 litters from the
supplier. However, because the relationship to treatment could not be
ruled out, the malformations were considered a possible treatment-
related effect.
No effects of treatment were reported in a 21-day repeated-
application dermal toxicity study in the rabbit. This is consistent
with relatively low dermal absorption (<=11% of administered dose)
observed in a dermal penetration study in the monkey and the low oral
toxicity observed in subchronic oral studies in the rat, mouse and dog.
Isoxaben is classified as having ``Suggestive Evidence of
Carcinogenic Potential'' based on an increased incidence of benign
liver tumors observed in male and female mice at the high dose only.
EPA has concluded that the chronic risk assessment, based on the
chronic RfD/PAD, is protective of potential carcinogenicity for the
following reasons. The liver tumors were observed only in one species
(mice), were not malignant, and were observed in the presence of liver
toxicity at dietary levels exceeding the limit dose (1,000 mg/kg/day).
The chronic RfD/PAD is based on the chronic toxicity NOAEL of 5 mg/kg/
day in the rat, which is more than 200-fold lower than the dose at
which tumors were observed in the mouse and, therefore, protective of
potential carcinogenicity.
Specific information on the studies received and the nature of the
adverse effects caused by isoxaben 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 the document ``Isoxaben. Human Health Risk
Assessment for the First Food Uses of the Herbicide on Grapes, Tree
Nuts and Pistachio'' at page 50 in docket ID number EPA-HQ-OPP-2007-
0504.
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 isoxaben used for
human risk assessment is shown in Table 1 of this unit.
Table 1--Summary of Toxicological Doses and Endpoints for Isoxaben 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 (All Populations, Not Applicable......... Not Applicable......... An appropriate endpoint
including Females 13-50 years of was not identified
age, Infants and Children). that could occur
following a single
exposure.
Chronic dietary (All populations).... NOAEL= 5.0 mg/kg/day Chronic RfD = 0.05 mg/ Chronic oral toxicity/
UFA = 10x UFH = 10x kg/day cPAD = 0.05 mg/ carcinogenicity in the
FQPA SF = 1x. kg/day. rat. LOAEL = 50.7 mg/
kg/day based on renal
toxicity in males.
Incidental oral short-term (1 to 30 Not Applicable......... Not Applicable......... An appropriate endpoint
days). was not identified for
short-term oral
exposures.
[[Page 69356]]
Incidental oral intermediate-term (1 NOAEL= 200 mg/kg/day LOC for MOE = 100...... Reproductive toxicity
to 6 months). UFA= 10x. in the rat (oral).
UFH= 10x FQPA SF = 1x.. Offspring LOAEL =
1,000 mg/kg/day based
on decreased body
weight gain in F1
females on Day 70.
One year dietary study
in the rat (co-
critical supporting
study). LOAEL = 625 mg/
kg/day based on
decreased body weight
gain in females during
the first six months
with a NOAEL of 62.5
mg/kg/day.
Dermal short-term (1 to 30 days)..... Not Applicable......... Not Applicable......... An appropriate endpoint
was not identified for
short-term dermal
exposures.
Dermal intermediate-term (1 to 6 Not Applicable......... Not Applicable......... An appropriate endpoint
months). was not identified for
intermediate-term
dermal exposures.
Inhalation short-term (1 to 30 days). Inhalation (or oral) LOC for MOE = 100...... Reproductive toxicity
study NOAEL= 200 mg/kg/ in the rat (oral).
day (inhalation LOAEL = 1,000 mg/kg/
absorption rate = day based on increased
100%). incidence of
UFA = 10x.............. malformations.
UFH = 10x..............
FQPA SF = 1x...........
Inhalation intermediate-term (1 to 6 Inhalation (or oral) LOC for MOE = 100...... Reproductive toxicity
months). study NOAEL = 200 mg/ in the rat (oral).
kg/day (inhalation LOAEL = 1,000 mg/kg/
absorption rate = day based on decreased
100%). body weight gain in F1
UFA = 10x.............. females on Day 70,
UFH = 10x.............. decreased F2 pup
FQPA SF = 1x........... weights, gestation
survival and live pups/
litter, and increased
incidence of
malformations.
One year dietary study
in the rat (co-
critical supporting
study). LOAEL = 625 mg/
kg/day based on
decreased body weight
gain in females during
the first six months
with a NOAEL of 62.5
mg/kg/day.
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Cancer (Oral, dermal, inhalation).... Classification: Suggestive Evidence of Carcinogenic Potential, based on
increased incidence of hepatocellular adenomas in male and female mice.
The chronic risk assessment, based on the chronic RfD/PAD, is considered
protective of potential carcinogenicity; a separate exposure assessment
to evaluate cancer risk is unnecessary.
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UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
of the human population (intraspecies). 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. LOAEL = lowest observed adverse effect level. NOAEL = no observed adverse effect level.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to isoxaben, EPA considered exposure under the petitioned-for
tolerances. There are no tolerances currently established for isoxaben.
EPA assessed dietary exposures from isoxaben 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. No such effects were
identified in the toxicological studies for isoxaben; therefore, a
quantitative acute dietary exposure assessment is unnecessary.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA 1994-1996
and 1998 Continuing Surveys of Food Intakes by Individuals (CSFII). As
to residue levels in food, EPA assumed that residues are present in all
commodities at the tolerance level and that 100% of commodities are
treated with isoxaben. DEEMTM 7.81 default concentration
factors were used to estimate residues of isoxaben in processed
commodities.
iii. Cancer. Based on the data summarized in Unit III.A., EPA
classified isoxaben as having ``Suggestive Evidence of Carcinogenic
Potential'' but determined that the chronic risk assessment will be
protective of both non-cancer and cancer effects. Therefore, a separate
exposure assessment to evaluate cancer risk is unnecessary.
iv. Anticipated residue and percent crop treated (PCT) information.
EPA did not use anticipated residue or PCT information in the dietary
assessment for isoxaben. Tolerance level residues and 100% CT were
assumed for all food commodities.
[[Page 69357]]
2. Dietary exposure from drinking water. The residues of concern in
drinking water following applications of isoxaben include isoxaben and
its degradates hydroxyisoxaben (N-[3-(1-hydroxyl-1-methylpropyl)-5-
isoxazoyl]-2,6-dimethoxy-benzamide); dimethoxybenzamide (2,6-
dimethoxybenzamide); methoxyphenylpyrimidinol (6-(1-ethyl-1-
methylpropyl)-2-(2-hydroxy-6-methoxyphenyl)-4-pyrimidinol); and AEM
hexenoylisoxaben (N-[3-amino-4-ethyl-4-methyl-2-hexenoyl]-2,6-
dimethoxybenzamide). The Agency used screening level water exposure
models in the dietary exposure analysis and risk assessment for
isoxaben and its degradates in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of isoxaben and its degradates. 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 isoxaben and its
degradates for chronic exposures for non-cancer assessments (the only
dietary exposure scenario of concern for isoxaben) are estimated to be
120 parts per billion (ppb) for surface water and 43.6 ppb for ground
water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For chronic dietary risk
assessment, the water concentration of value 120 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). Isoxaben is currently
registered for the following uses that could result in residential
exposures: Home lawns, recreational turf areas and ornamental
plantings. EPA assessed residential exposure using the following
assumptions: There is a potential for exposure of homeowners applying
products containing isoxaben on home lawns (i.e., residential handler
exposure). There is also a potential for post-application exposure of
adults and children entering lawn and recreation areas which have been
treated with isoxaben and for bystander exposure of adults and children
in areas adjacent to pesticide applications.
For residential handlers, dermal and inhalation exposures of short-
term duration are expected. Since EPA did not identify an endpoint of
concern for dermal exposures, only short-term inhalation exposures were
assessed.
The following types of residential exposure may occur following
applications of isoxaben on lawns and recreational turf areas: Short-
and intermediate-term dermal and inhalation exposure of adults and
children entering treated areas; short-term incidental oral hand-to-
mouth and/or object-to-mouth exposure of children playing on treated
turf; short- and intermediate-term incidental oral exposure of children
ingesting soil from treated areas; and episodic oral exposure of
children ingesting pesticide granules following applications of
granular isoxaben formulations on lawns. Post-application inhalation
exposures are expected to be negligible due to the low volatility of
isoxaben, label recommendations for incorporation of the product (by
rainfall or irrigation) after application, and the types of application
equipment used to apply isoxaben (i.e., isoxaben is not applied using
air blast or aerial equipment that would increase the potential for
inhalation exposure). EPA did not identify an endpoint of concern for
acute or short-term oral exposures or for short- or intermediate-term
dermal exposures. Therefore, in its post-application exposure
assessment for isoxaben, EPA assessed only intermediate-term oral
exposure of children ingesting treated soil. EPA does not typically
consider soil ingestion to occur over intermediate-term durations,
i.e., from 1-6 months, largely due to use patterns and the fact that
residues are removed by precipitation or through microbial degradation
in soil. In the case of isoxaben, the Agency estimated incidental oral
exposure from ingestion of soil because the use pattern calls for
repeat applications and the environmental fate data indicate that
isoxaben is persistent in the soil. EPA conducted a conservative
assessment of potential intermediate-term oral risk from soil ingestion
using an application rate of 3.0 lb ai/A, equivalent to 3X the maximum
single rate of 1.0 lb ai/A. The higher rate was assumed to account for
build-up in the soil due to the pesticide's persistence.
Bystander exposure of adults and children is possible on areas
adjacent to application sites. EPA's concern for bystander exposures is
low based on several considerations:
i. Low acute toxicity of isoxaben via the inhalation route of
exposure;
ii. Label recommendations for incorporation of the product (by
rainfall or irrigation) after application;
iii. Isoxaben's low volatility; and
iv. The types of application equipment used to apply isoxaben
(i.e., isoxaben is not applied using air blast or aerial equipment that
would increase the potential for inhalation exposure).
In addition, EPA notes that MOEs calculated for residential
handlers of isoxaben are very high, ranging from 2.9 million to 28
million (See Unit III.E.3.). Bystander exposures of both adults and
children are expected to be substantially lower than residential
handler exposures, resulting in even higher MOEs and lower risk for
bystanders. For these reasons, EPA's concern for bystander exposure of
adults and children is low, and a quantitative assessment of bystander
exposure and risk is considered unnecessary.
Further information regarding EPA standard assumptions and generic
inputs for residential exposures may be found at http://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
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.''
EPA has not found isoxaben to share a common mechanism of toxicity
with any other substances, and isoxaben does not appear to produce a
toxic metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has assumed that isoxaben does not
have a common mechanism of toxicity with other substances. 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 Web site at http://www.epa.gov/pesticides/cumulative.
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
[[Page 69358]]
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. The pre- and postnatal
toxicity database for isoxaben includes guideline rat and rabbit
developmental toxicity studies and a three-generation reproduction
toxicity study in rats. There was no maternal or developmental toxicity
observed in the developmental studies in rats and rabbits. Increased
qualitative susceptibility was observed in the rat reproductive
toxicity study as decreased live pups/litter and decreased gestation
survival in F2b litters (relative to body weight effects in
mothers).
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. That decision is based on the following
findings:
i. The toxicity database for isoxaben is largely complete, missing
only acute and subchronic neurotoxicity studies, an immunotoxicity
study and a subchronic inhalation study. EPA has determined that an
additional uncertainty factor is not needed to account for the lack of
these studies for the following reasons:
There is no evidence in the existing studies that isoxaben
targets either the nervous system or the immune system.
EPA's concern for inhalation toxicity from subchronic
exposures is low, based on isoxaben's low vapor pressure and frequency
of application.
Overall, the toxicity of isoxaben is low. The available
oral studies of short-term (e.g., developmental toxicity) or subchronic
exposure duration indicated no toxicity up to the limit dose. Effects
observed in adult animals (decreased body weight) at exposures of
intermediate-term duration were minimal, and malformations seen in
offspring in the rat reproduction study were of uncertain relationship
to treatment. The endpoints were assumed by EPA to be treatment-
related, a conservative assumption intended to ensure the risk
assessment is protective of potential effects.
Based on these considerations, EPA does not expect the required studies
to provide lower points of departure than those currently selected for
risk assessment, and an additional uncertainty factor is not needed to
account for the lack of these studies.
ii. There is no evidence of neurotoxicity in the available
toxicology database and no evidence of developmental toxicity in either
the rat or rabbit developmental toxicity studies at doses up to the
limit dose. Based on these considerations, there is no need for a
developmental neurotoxicity study or additional UFs to account for
neurotoxicity.
iii. There was no evidence of increased susceptibility in the rat
and rabbit developmental toxicity studies. Although increased
qualitative susceptibility was observed in the rat reproductive
toxicity study as decreased live pups/litter and decreased gestation
survival in F2b litters (relative to body weight effects in
mothers), EPA's concern for qualitative susceptibility is low.
Offspring effects were seen only at the limit dose in later generations
and not observed in the developmental studies. Additionally, since
there is evidence that observed malformations were due in part to
heritable factors, the relationship of these effects to treatment is
unclear. There are low concerns for effects on offspring viability,
because they were only observed at the limit dose and may have been
secondary to effects on the dams. The endpoints and points of departure
selected for risk assessment are protective of these effects.
iv. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed
assuming tolerance-level residues and 100% crop treated for all
commodities. EPA made conservative (protective) assumptions in the
ground and surface water modeling used to assess exposure to isoxaben
in drinking water. EPA used similarly conservative assumptions to
assess postapplication exposure of children as well as incidental oral
exposure of toddlers. These assessments will not underestimate the
exposure and risks posed by isoxaben.
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. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. No adverse effect resulting from a single oral exposure
was identified and no acute dietary endpoint was selected. Therefore,
isoxaben is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
isoxaben from food and water will utilize 17% of the cPAD for infants,
less than 1 year old, the population group receiving the greatest
exposure. Based on the explanation in Unit III.C.3., regarding
residential use patterns, chronic residential exposure to residues of
isoxaben is not expected.
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). Isoxaben is
currently registered for uses that could result in short-term
residential exposure, and the Agency has determined that it is
appropriate to aggregate chronic exposure through food and water with
short-term residential exposures to isoxaben.
Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water,
and residential exposures result in an aggregate MOE of 82,000 for
adults. The MOE for adults includes chronic exposure from food and
water plus short-term residential handler exposure of adult females,
based on the worst-case granular push-type applicator scenario. Because
EPA's level of concern for isoxaben is a MOE of 100 or below, this MOE
is not of concern. For children, no short-term oral or dermal endpoints
of concern were identified, and residential post-application inhalation
exposure is expected to be negligible. Therefore, EPA relies on the
chronic dietary risk assessment discussed in Unit III.E.2. for
evaluating children's short-term risk from isoxaben.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level). Isoxaben is currently registered for uses that could result in
intermediate-term residential exposure, and the Agency has determined
that it is appropriate to aggregate chronic exposure through food and
water with intermediate-term residential exposures to isoxaben.
Using the exposure assumptions described in this unit for
intermediate-
[[Page 69359]]
term exposures, EPA has concluded that the combined intermediate-term
food, water, and residential exposures result in an aggregate MOE of
51,000 for children. The MOE for children includes chronic exposure
from food and water plus intermediate-term oral exposure of children
ingesting treated soil. Because EPA's level of concern for isoxaben is
a MOE of 100 or below, the MOE for children is not of concern. For
adults, no intermediate-term dermal endpoint of concern was identified,
and residential post-application inhalation exposure is expected to be
negligible. Therefore, EPA relies on the chronic dietary risk
assessment discussed in Unit III.E.2. for evaluating adults'
intermediate-term risk from isoxaben.
5. Aggregate cancer risk for U.S. population. As explained in Unit
III.A., risk assessments based on the endpoint selected for chronic
risk assessment are considered to be protective of any potential
carcinogenic risk from exposure to isoxaben. Based on the results of
the chronic risk assessment discussed above in Unit III.E.2., EPA
concludes that isoxaben is not expected to pose a cancer risk.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, or to infants and children from aggregate
exposure to isoxaben residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (high-performance liquid
chromatography with tandem mass spectromectric detection (LC/MS/MS),
method GRM 02.26.S.1) 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:
[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 isoxaben.
C. Revisions to Petitioned-For Tolerances
Based on the maximum residue of 0.015 ppm observed in field trials
with almonds and pecans, the proposed tolerances for nut, tree, group
14 and pistachio were reduced from 0.03 ppm to 0.02 ppm. The proposed
tolerance for almond hulls was increased from 0.35 ppm to 0.40 ppm
based on analysis of the field trial data using the Agency's Tolerance
Spreadsheet in accordance with the ``Guidance for Setting Pesticide
Tolerances Based on Field Trial Data.'' EPA has also determined that,
since the tolerance for grape will cover residues in/on grape juice and
raisins, separate tolerances are not needed for these commodities.
Finally, EPA is revising the requested tolerance expression to
clarify the chemical moieties that are covered by the tolerances and
specify how compliance with the tolerances is to be measured. The
revised tolerance expression makes clear that the tolerances cover
residues of the herbicide isoxaben, including its metabolites and
degradates, but that compliance with the specified tolerance levels is
to be determined by measuring only isoxaben N-[3-(1-ethyl-1-
methylpropyl)-5-isoxazolyl]-2, 6-dimethoxybenzamide, in or on the
commodities.
V. Conclusion
Therefore, tolerances are established for residues of isoxaben,
including its metabolites and degradates, in or on almond, hulls at
0.40 ppm; grape at 0.01 ppm; nut, tree, group 14 at 0.02 ppm; and
pistachio at 0.02 ppm. Compliance with these tolerances is to be
determined by measuring only isoxaben N-[3-(1-ethyl-1-methylpropyl)-5-
isoxazolyl]-2, 6-dimethoxybenzamide, in or on the commodities.
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).
[[Page 69360]]
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: October 29, 2010.
Steven Bradbury,
Director, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. Add Sec. 180.650 to subpart C to read as follows:
Sec. 180.650 Isoxaben; tolerances for residues.
(a) General. Tolerances are established for residues of the
herbicide isoxaben, 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 isoxaben,
N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2, 6-dimethoxybenzamide, in
or on the commodity.
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Almond, hulls........................................... 0.40
Grape................................................... 0.01
Nut, tree, Group 14..................................... 0.02
Pistachio............................................... 0.02
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 2010-28499 Filed 11-10-10; 8:45 am]
BILLING CODE 6560-50-P