Document ID: EPA-HQ-OPP-2009-0823-0003
Agency: epa
Document Type: Rule
Title: Pesticide Tolerances: Difenoconazole
Posted Date: 2011-03-02T05:00Z

[Federal Register Volume 76, Number 41 (Wednesday, March 2, 2011)]
[Rules and Regulations]
[Pages 11344-11350]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-4370]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2009-0823; FRL-8864-9]

Difenoconazole; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
difenoconazole in or on mango and wax jambu. Syngenta Crop Protection, 
Incorporated requested these tolerances under the Federal Food, Drug, 
and Cosmetic Act (FFDCA).

DATES: This regulation is effective March 2, 2011. Objections and 
requests for hearings must be received on or before May 2, 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-2009-0823. 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: Tony Kish, Registration Division, 
Office of Pesticide Programs, Environmental Protection Agency, 1200 
Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: 
(703) 308-9443; e-mail address: kish.tony@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to 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.

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-2009-0823 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 
May 2, 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-2009-0823, 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 Tolerances

    In the Federal Register of January 6, 2010 (75 FR 864) (FRL-8801-
5), 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 
9E7573) by Syngenta Crop Protection, Inc., P. O. Box 18300, Greensboro, 
NC 27419. The petition requested that 40 CFR 180.475 be amended by 
establishing tolerances for residues of the fungicide, difenoconazole, 
[1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-
ylmethyl]-1H-1,2,4-triazole], in or on mango at 0.09 parts per 
million(ppm) and waxapple at 1.5 ppm. That notice referenced a summary 
of the petition prepared by Syngenta Crop Protection, Inc., 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 
revised the proposed tolerance for mango, fruit from 0.09 ppm to 0.07 
ppm to reflect the Agency's recommended tolerance level. Additionally, 
EPA corrected commodity definitions from ``mango, fruit'' to ``mango'' 
and ``waxapple'' to ``wax jambu'' to reflect prescribed terminology. 
The reasons for these changes are explained in Unit IV.D.

[[Page 11345]]

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 difenoconazole including 
exposure resulting from the tolerances established by this action. 
EPA's assessment of exposures and risks associated with difenoconazole 
follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered their 
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.
    Difenoconazole possesses low acute toxicity by the oral, dermal and 
inhalation routes of exposure. It is not considered to be an eye or 
skin irritant and is not a dermal sensitizer.
    In an acute neurotoxicity study in rats, reduced fore-limb grip 
strength was observed on day 1 in males and clinical signs of 
neurotoxicity in females at the limit dose of 2,000 milligrams/kilogram 
(mg/kg). This effect in males is considered as transient since it was 
not observed at later observation points and toxicity in females was 
observed only at doses exceeding the limit dose. In a subchronic 
neurotoxicity study in rats decreased hind limb strength was observed 
only in males, which was considered as nonspecific in nature.
    Difenoconazole is not a developmental or reproductive toxicant. 
Chronic effects in mice and rat studies are seen as cumulative 
decreases in body weight gains.
    Difenoconazole is not mutagenic. Evidence for carcinogenicity was 
seen only in the mice study, where liver tumors were induced at 
excessively high doses for carcinogenicity testing. Liver tumors were 
observed in mice at 300 ppm and higher. Based on excessive toxicity 
observed at the two highest doses of 2,500 and 4,500 ppm, the absence 
of tumors at two lower doses of 10 and 30 ppm, as well as, the absence 
of genotoxic effects, the Agency classified difenoconazole as a Group 
C, possible human carcinogen with a non-linear margin-of-exposure (MOE) 
approach for human risk characterization.
    Specific information on the studies received and the nature of the 
adverse effects caused by difenoconazole as well as the no-observed-
adverse-effects-level (NOAEL) and the lowest-observed-adverse-effects-
level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in the document entitled, ``Difenoconazole FQPA 
Human Health Risk Assessment to Support the Establishment of Import 
Tolerances on Mango and Waxapple (also known as Wax jambu),'' at pages 
28-35, dated January 28, 2010, Document No. EPA-HQ-OPP-2009-0823-003.

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 difenoconazole used 
for human risk assessment is shown in the following Table.

 Table--Summary of Toxicological Doses and Endpoints for Difenoconazole 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 (All populations)....  NOAEL = 25 mg/kg/day..  aRfD = 0.25 mg/kg/day.  Acute Neurotoxicity Study
                                     UFA = 10x.............  aPAD = 0.25 mg/kg/day.   in rats LOAEL = 200 mg/kg/
                                     UFH = 10x.............                           day in males based on
                                     FQPA SF = 1x..........                           reduced fore-limb grip
                                                                                      strength in males on day
                                                                                      1.
Chronic dietary (All populations)..  NOAEL = 0.96 mg/kg/day  cRfD = 0.01 mg/kg/day.  Combined chronic toxicity/
                                     UFA = 10x.............  cPAD = 0.01 mg/kg/day.   carcinogenicity (rat;
                                     UFH = 10x.............                           dietary) LOAEL = 24.1/32.8
                                     FQPA SF = 1x..........                           mg/kg/day (M/F) based on
                                                                                      cumulative decreases in
                                                                                      body-weight gains.

[[Page 11346]]

 
Dermal short-term (1 to 30 days)     Oral NOAEL = 1.25 mg/   Residential LOC for     Reproduction and fertility
 and intermediate-term (1 to 6        kg/day (dermal          MOE = < 100.            effects (rat; dietary)
 months).                             absorption factor =                             Offspring LOAEL = 12.5 mg/
                                      15.3%).                                         kg/day based on reduction
                                     UFA = 10x.............                           in body weight of F0
                                     UFH = 10x.............                           females prior to mating,
                                     FQPA SF = 1x..........                           gestation and lactation.
Inhalation short-term (1 to 30       Oral NOAEL= 1.25 mg/kg/ Residential LOC for     Reproduction and fertility
 days) and Intermediate-term          day inhalation          MOE < 100.              effects (rat; dietary)
 Inhalation (1 to 6 months).          absorption rate =                               Offspring LOAEL = 12.5 mg/
                                      assumed as 100%                                 kg/day based on reduction
                                     UFA = 10x.............                           in body weight of F0
                                     UFH = 10x.............                           females prior to mating,
                                     FQPA SF = 1x..........                           gestation and lactation.
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)..  Difenoconazole is classified as a Group C, possible human carcinogen with a
                                              non-linear (MOE) approach for human risk characterization.
----------------------------------------------------------------------------------------------------------------
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.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to difenoconazole, EPA considered exposure under the 
petitioned-for tolerances as well as all existing difenoconazole 
tolerances in 40 CFR 180.475. EPA assessed dietary exposures from 
difenoconazole 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 difenoconazole. 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 tolerance-level residues, 100 
percent crop treated (PCT), and the available empirical or Dietary 
Exposure Evaluation Model (DEEMTM) (ver. 7.81) default 
processing factors.
    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 tolerance-
level residues for some commodities, average field trial residues for 
the majority of commodities, the available empirical or 
DEEMTM (ver. 7.81) default processing factors, and 100 PCT.
    iii. Cancer. No evidence of carcinogenicity was seen in rats. 
Evidence for carcinogenicity was seen in mice, where liver tumors were 
induced at doses which were considered to be excessively high for 
carcinogenicity testing. Liver tumors were observed in mice at 300 ppm 
and higher; however, based on excessive toxicity observed at the two 
highest doses of 2,500 and 4,500 ppm (females terminated after 2 weeks 
due to excessive toxicity resulting in moribundity and death), the 
absence of tumors at two lower doses of 10 and 30 ppm and the absence 
of genotoxic effects, the Agency classified difenoconazole as a Group 
C, possible human carcinogen with a non-linear MOE approach for human 
risk characterization. A MOE approach in risk assessment was chosen 
utilizing the NOAEL of 30 ppm (4.7 and 5.6 mg/kg/day in males and 
females, respectively) and the LOAEL of 300 ppm (46 and 58 mg/kg/day in 
males and females, respectively) from the mouse study using only those 
biological endpoints which were relevant to tumor development (i.e., 
hepatocellular hypertrophy, liver necrosis, fatty changes in the liver 
and bile stasis). However, EPA determined that a quantitative cancer 
exposure assessment is unnecessary since the NOAEL (4.7 and 5.6 mg/kg/
day in males and females, respectively) to assess cancer risk is higher 
than the NOAEL (0.96 and 1.27 mg/kg/day in males and females, 
respectively) to assess chronic risks. Therefore, the chronic dietary 
risk estimate will be protective of potential cancer risk.
    iv. Anticipated residues and percent crop treated (PCT) 
information. EPA did not use PCT information in the dietary assessment 
of difenoconazole. EPA used anticipated residues including average 
field trial residues for the majority of commodities, the available 
empirical or DEEMTM (ver. 7.81) default processing factors; 
and 100 PCT information in the chronic dietary assessment for 
difenoconazole.
    Section 408(b)(2)(E) of FFDCA authorizes EPA to use available data 
and information on the anticipated residue levels of pesticide residues 
in food and the actual levels of pesticide residues that have been 
measured in food. If EPA relies on such information, EPA must require, 
pursuant to FFDCA section 408(f)(1), that data be provided 5 years 
after the tolerance is established, modified, or left in effect, 
demonstrating that the levels in food are not above the levels 
anticipated. For the present action, EPA will issue such data call-ins 
as are required by FFDCA section 408(b)(2)(E) and authorized under 
FFDCA section 408(f)(1). Data will be required to be submitted no later 
than 5 years from the date of issuance of these tolerances.
    2. Dietary exposure from drinking water. Although the subject 
petition is for import tolerances and therefore does not result in 
drinking water exposure, there are existing uses of difenoconazole 
registered in the United States. The drinking water assessment was 
conducted for parent compound only. The fate and transport database for 
difenoconazole were sufficient to conduct the drinking water 
assessment.
    The Agency used screening level water exposure models in the 
dietary exposure analysis and risk assessment for difenoconazole in 
drinking water. These simulation models take into

[[Page 11347]]

account data on the physical, chemical, and fate/transport 
characteristics of difenoconazole. Further information regarding EPA 
drinking water models used in pesticide exposure assessment can be 
found at http://www.epa.gov/oppefed1/models/water/index.htm.
    Based on the Pesticide Root Zone Model/Exposure Analysis Modeling 
System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-
GROW) models, the estimated drinking water concentrations (EDWCs) of 
difenoconazole for acute exposures are estimated to be 15.8 parts per 
billion (ppb) for surface water and 0.0128 ppb for ground water.
    Chronic exposures for non-cancer assessments are estimated to be 
10.4 ppb for surface water and 0.0128 ppb for ground water.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model.
    For acute dietary risk assessment, the water concentration value of 
15.8 ppb was used to assess the contribution to drinking water.
    For chronic dietary risk assessment, the water concentration of 
value 10.4 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).
    Difenoconazole is currently registered for the following uses that 
could result in residential exposures: Ornamentals. EPA assessed 
residential exposure using the following assumptions: Adults may be 
exposed to difenoconazole from its currently registered use on 
ornamentals. Residential pesticide handlers may be exposed to short-
term duration (1-30 days) only. The dermal and inhalation (short-term) 
residential exposure was assessed for ``homeowners'' mixer/loader/
applicator wearing short pants and short-sleeved shirts as well as 
shoes plus socks using garden hose-end sprayer, ``pump-up'' compressed 
air sprayer, and backpack sprayer.
    No post-application exposure is expected. 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.''
    Difenoconazole is a member of the triazole-containing class of 
pesticides. Although conazoles act similarly in plants (fungi) by 
inhibiting ergosterol biosynthesis, there is not necessarily a 
relationship between their pesticidal activity and their mechanism of 
toxicity in mammals. Structural similarities do not constitute a common 
mechanism of toxicity. Evidence is needed to establish that the 
chemicals operate by the same, or essentially the same, sequence of 
major biochemical events. In conazoles, however, a variable pattern of 
toxicological responses is found. Some are hepatotoxic and 
hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some 
induce developmental, reproductive, and neurological effects in 
rodents. Furthermore, the conazoles produce a diverse range of 
biochemical events including altered cholesterol levels, stress 
responses, and altered DNA methylation. It is not clearly understood 
whether these biochemical events are directly connected to their 
toxicological outcomes. Thus, there is currently no evidence to 
indicate that conazoles share common mechanisms of toxicity and EPA is 
not following a cumulative risk approach based on a common mechanism of 
toxicity for the conazoles. For information regarding EPA's procedures 
for cumulating effects from substances found to have a common mechanism 
of toxicity, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.
    Difenoconazole is a triazole-derived pesticide. This class of 
compounds can form the common metabolite 1,2,4-triazole and two 
triazole conjugates (triazolylalanine and triazolylacetic acid). To 
support existing tolerances and to establish new tolerances for 
triazole-derivative pesticides, including difenoconazole, EPA conducted 
a human health risk assessment for exposure to 1,2,4-triazole, 
triazolylalanine, and triazolylacetic acid resulting from the use of 
all current and pending uses of any triazole-derived fungicide. The 
risk assessment is a highly conservative, screening-level evaluation in 
terms of hazards associated with common metabolites (e.g., use of a 
maximum combination of uncertainty factors) and potential dietary and 
non-dietary exposures (i.e., high end estimates of both dietary and 
non-dietary exposures). In addition, the Agency retained the additional 
10X FQPA safety factor for the protection of infants and children. The 
assessment includes evaluations of risks for various subgroups, 
including those comprised of infants and children. The Agency's 
complete risk assessment is found in the propiconazole reregistration 
docket at http://www.regulations.gov, Docket Identification (ID) Number 
EPA-HQ-OPP-2005-0497.

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. EPA determined that the 
available data indicated no increased susceptibility of rats or rabbits 
to in utero and/or postnatal exposure to difenoconazole. In the 
prenatal developmental toxicity studies in rats and rabbits and the 2-
generation reproduction study in rats, toxicity to the fetuses/
offspring, when observed, occurred at equivalent or higher doses than 
in the maternal/parental animals. In the prenatal developmental 
toxicity study in rats, maternal toxicity was manifested as decreased 
body weight gain and food consumption at the LOAEL of 85 mg/kg/day; the 
NOAEL was 16 mg/kg/day. The developmental toxicity was manifested as 
alterations in fetal ossifications at 171 mg/kg/day; the developmental 
NOAEL was 85 mg/kg/day. In a developmental toxicity study in rabbits, 
maternal and developmental toxicity were seen at the same dose level 
(75 mg/kg/day). Maternal toxicity in rabbits were manifested as 
decreased body weight gain and decreased food consumption, while 
developmental toxicity was manifested as decreased fetal weight. In a 
2-generation reproduction study in rats, there were decreases in 
maternal body weight gain and decreases in body weights of 
F1 males at the LOAEL of 12.5 mg/kg/day; the parental 
systemic and off spring toxicity NOAEL was 1.25 mg/kg/day.
    3. Conclusion. EPA has determined that reliable data show the 
safety of infants and children would be adequately protected if the 
FQPA SF

[[Page 11348]]

were reduced to 1x. That decision is based on the following findings:
    i. The toxicity database is adequate for conducting a FQPA risk 
assessment. At this time, an immunotoxicity study is not available. 
However, the toxicology database for difenocanazole does not show any 
evidence of treatment-related effects on the immune system. The overall 
weight of evidence suggests that this chemical does not directly target 
the immune system. An immunotoxicity study is now required as a part of 
new data requirements in the 40 CFR part 158 for conventional pesticide 
registration; however, the Agency does not believe that conducting a 
functional immunotoxicity study will result in a lower point of 
departure (POD) than that currently in use for overall risk assessment, 
and therefore, a database uncertainty factor (UFDB) is not needed to 
account for lack of this study.
    ii. The acute and subchronic neurotoxicity studies in rats are 
available. These data show that difenoconazole exhibits some evidence 
of neurotoxicity in the database, but the effects are transient or 
occur at doses exceeding the limit dose. EPA concluded that 
difenoconazole is not a neurotoxic compound. Based on the toxicity 
profile, and lack of neurotoxicity, a developmental neurotoxicity study 
in rats is not required nor is an additional database uncertainty 
factor needed to account for the lack of this study.
    iii. There is no evidence that difenoconazole results in increased 
susceptibility of rats or rabbit fetuses to in utero and/or postnatal 
exposure in the developmental and reproductive toxicity data.
    iv. There are no residual uncertainties identified in the exposure 
databases. A conservative dietary food exposure assessment was 
conducted. Acute dietary food exposure assessments were performed based 
on tolerance-level residues, 100 PCT, and the available empirical or 
DEEMTM (ver. 7.81) default processing factors. Chronic 
dietary exposure assessments were based on tolerance-level residues for 
some commodities, average field trial residues for the majority of 
commodities, the available empirical or DEEMTM (ver. 7.81) 
default processing factors, and 100 PCT. These are conservative 
approaches and are unlikely to understate the residues in food 
commodities.
    EPA also made conservative (protective) assumptions in the ground 
water and surface water modeling used to assess exposure to 
difenoconazole in drinking water. Post-application exposure of children 
as well as incidental oral exposure of toddlers is not expected. These 
assessments will not underestimate the exposure and risks posed by 
difenoconazole.

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. Cancer risk was assessed using the same exposure 
estimates as discussed in Unit III.C.1.ii., ``chronic exposure.''
    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food and water 
to difenoconazole will occupy 16% of the aPAD for children 1 to 2 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 
difenoconazole from food and water will utilize 45% of the cPAD for 
children 1 to 2 years 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 
difenoconazole 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).
    Difenoconazole is currently registered for ornamentals 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 difenoconazole.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded that the combined short-term food, 
water, and residential exposures result in aggregate MOEs of 180 or 
greater. Because EPA's level of concern for difenoconazole is a MOE of 
100 or below, these MOEs resulting from short-termed exposure to 
difenoconazole are not of concern.
    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).
    An intermediate-term adverse effect was identified; however, 
difenoconazole 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 
difenoconazole.
    5. Aggregate cancer risk for U.S. population. As discussed in Unit 
III.C.1.iii., the chronic dietary risk assessment is protective of any 
potential cancer effects.
    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, or to infants and children from aggregate 
exposure to difenoconazole residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    An adequate tolerance enforcement method, method AG-575B, is 
available to enforce the tolerance expression. The method determines 
residues of difenoconazole per se in or on crop commodities by gas 
chromatography with nitrogen-phosphorus detection (GC/NPD). The 
method's limits of quantitation (LOQs) are 0.01-0.05 ppm. A 
confirmatory GC method with mass-selective detection (MSD) is also 
available for crop commodities. Samples from the submitted crop field 
trials were analyzed for residues of difenoconazole using a high 
performance liquid chromatography method with tandem mass spectrometry 
detection (LC/MS/MS), Syngenta REM 147.08, or a similar method. The 
methods are adequate for data collection based on acceptable concurrent 
method recoveries. The LOQ was 0.01 ppm for difenoconazole in mango and 
wax jambu.
    The method may be requested from: Chief, Analytical Chemistry 
Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 
20755-5350; telephone number: (410) 305-2905; e-mail address: 
residuemethods@epa.gov.

[[Page 11349]]

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 established a MRL for difenoconazole in or on mango 
at 0.07 ppm. This MRL is the same as the tolerance established by this 
action for difenoconzole in the United States. Canadian and Mexican 
MRLs have been established for difenoconazole; however, no MRLs have 
been established for mango. No Codex, Canadian, and Mexican MRLs have 
been established for residues of difenoconazole in or on wax jambu.

C. Response to Comments

    There were no public comments received on the Notice of Filing.

D. Revisions to Petitioned-For Tolerances

    EPA has revised the tolerance levels proposed in the notice of 
filing for mango from 0.09 ppm to 0.07 ppm. The modification was made 
based on the available data supporting the use of difenoconazole on 
mango and to achieve harmonization with the established Codex MRL of 
0.07 ppm residues in or on mango.
    Also, the Agency corrected the commodities named in the notice from 
``mango fruit'' to ``mango'' and ``waxapple'' to ``wax jambu'' to 
reflect EPA's prescribled terminology for these crops.

V. Conclusion

    Therefore, tolerances are established for residues of 
difenoconazole, 1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-
dioxolan-2-ylmethyl]-1H-1,2,4-triazole, in or on mango at 0.07 ppm and 
wax jambu at 1.5 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 
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: February 18, 2011.
Daniel J. Rosenblatt,
Acting 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 180.475 is amended by alphabetically adding the following 
commodities to the table in paragraph (a)(1) to read as follows:

Sec.  180.475  Difenoconazole; tolerance for residues.

    (a) * * *
    (1) * * *

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
 
                                * * * * *
Mango \1\.................................................          0.07
 
                                * * * * *
Wax jambu \1\.............................................          1.5
------------------------------------------------------------------------

[[Page 11350]]

* * * * *
[FR Doc. 2011-4370 Filed 3-1-11; 8:45 am]
BILLING CODE 6560-50-P