[Federal Register Volume 76, Number 115 (Wednesday, June 15, 2011)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-14770]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Difenoconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of
difenoconazole in or on aspirated grain fractions; carrot; chickpea;
fruits, stone, group 12; soybean, hulls; soybean, seed; strawberry; and
turnip greens. Syngenta Crop Protection, Inc., requested these
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA). This
regulation also increases the existing tolerances for cattle, liver;
goat, liver; hog, liver; horse, liver; sheep, liver; and decreases the
existing tolererance for egg and revises the tolerance expression for
DATES: This regulation is effective June 15, 2011. Objections and
requests for hearings must be received on or before August 15, 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-2010-0296. 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: Rose Mary Kearns, Registration
Division (7505P), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-5611; e-mail 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://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-2010-0296 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
August 15, 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-2010-0296, 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 4, 2010 (75 FR 46924) (FRL-8834-
9), 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
9F7676) by Syngenta Crop Protection, Inc., P.O. Box 18300, Greensboro,
NC 27419-8300. The petition requested that 40 CFR 180.475 be amended by
establishing tolerances for residues of the fungicide difenoconazole,
in or on carrot at 0.45 parts per million (ppm); chickpeas at 0.05 ppm;
fruits, stone, group 12 at 2.5 ppm; soybean, seed, at 0.2 ppm; soybean,
aspirated grain fraction at 95 ppm; strawberry at 2.5 ppm; turnip
greens at 35 ppm; and increasing the existing milk tolerance from 0.01
to 0.08 ppm. Comments were received on the notice of filing. EPA's
response to these comments is discussed in Unit IV.C.
Based upon review of the data supporting the petition, EPA has:
Increased the proposed tolerance for carrot from 0.45 ppm to 0.50 ppm,
and for chickpea from 0.05 ppm to 0.08 ppm; decreased the proposed
soybean, seed tolerance from 0.20 ppm to 0.15 ppm; established a
tolerance that was not proposed for soybean, hulls at 0.20 ppm; changed
the proposed tolerance terminology for ``soybean, aspirated grain
fractions'' to ``aspirated grain fractions;'' revised the tolerance
expression for animal commodities; increased the existing animal
tolerances from 0.20 ppm to 0.40 ppm for the livers of cattle, goat,
hog, horse, and sheep; decreased the existing tolerance for eggs from
0.10 ppm to 0.02 ppm; not granted the proposed tolerance increase for
milk from 0.01 to 0.08 ppm. The reasons for these changes are explained
in Unit IV.D.
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
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
Difenoconazole possesses low acute toxicity by the oral, dermal and
inhalation routes of exposure. It is not an eye or skin irritant and is
not a sensitizer. Subchronic and chronic studies with difenoconazole in
mice and rats showed decreased body weights, decreased body weight
gains and effects on the liver. In an acute neurotoxicity study in
rats, reduced fore-limb grip strength was observed on day 1 in males
and clinical signs of neurotoxicity were observed in females at the
limit dose of 2,000 milligrams/kilograms (mg/kg). In a subchronic
neurotoxicity study in rats, decreased hind limb strength was observed
in males only at the mid- and high-doses. However, the effects observed
in acute and subchronic neurotoxicity studies are transient, and the
dose-response is well characterized with identified no observed adverse
effect level (NOAELs). No systemic toxicity was observed at the limit
dose in the most recently submitted 28-day rat dermal toxicity study.
There is no concern for increased qualitative and/or quantitative
susceptibility after exposure to difenoconazole based on developmental
toxicity studies in rats and rabbits, and a reproduction study in rats
as fetal/offspring effects occurred in the presence of maternal
toxicity. There are no indications in the available studies that organs
associated with immune function, such as the thymus and spleen, are
affected by difenoconazole.
In accordance with the Agency's current policy, difenoconazole is
classified as ``Suggestive Evidence of Carcingenic Potential'' and EPA
is using the Margin of Exposure (MOE) approach to assess cancer risk.
Difenoconazole is not mutagenic, and no evidence of carcinogenicity was
seen in rats. Evidence for carcinogenicity was seen in mice (liver
tumors), but these tumors were only induced at doses which were
considered to be excessively high for carcinogenicity testing. Based on
excessive toxicity observed at the two highest doses in the study, the
absence of tumors at the study's lower doses, and the absence of
genotoxic effects, EPA has concluded that the chronic point of
departure (POD) from the chronic mouse study will be protective of any
cancer effects. The POD from this study is the NOAEL of 30 ppm (4.7 and
5.6 mg/kg/day in males and females, respectively) which was chosen
based upon only those biological endpoints which were relevant to tumor
development (i.e., hepatocellular hypertrophy, liver necrosis, fatty
changes in the liver and bile stasis).
Specific information on the studies received and the nature of the
adverse effects caused by difenoconazole as well as the NOAEL and the
lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies
can be found at http://www.regulations.gov in document ``Difenoconazole
Human Health Risk Assessment for Amended Section 3 Registration to Add
Uses on Carrots, Chickpeas, Soybeans, Stone Fruits (Group 12),
Strawberries, Turnip Greens and Golf Course Turf Grass,'' pp. 13-19 in
docket ID number EPA-HQ-OPP-2010-0296.
B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA
identifies toxicological 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 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 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 chemical name used for
human risk assessment is shown in the Table of this unit.
Table--Summary of Toxicological Doses and Endpoints for Difenoconazole for Use in Human Health Risk Assessment
Point of departure
Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effects
safety factors risk assessment
Acute dietary--General population NOAEL = 25 mg/kg.... Acute RfD = 0.25 mg/ Acute Neurotoxicity study in Rats
including infants and children. UFA = 10x........... kg/day. LOAEL = 200 mg/kg/day based on
UFH = 10x........... aPAD = 0.25 mg/kg/ reduced fore-limb grip strength
FQPA SF = 1x........ day. in males on day 1.
Chronic dietary--All populations. NOAEL= 0.96 mg/kg/ Chronic RfD = 0.01 Combined chronic toxicity/
day. mg/kg/day. carcinogenicity (rat; dietary)
UFA = 10x........... cPAD = 0.01 mg/kg/ LOAEL = 24.1/32.8 mg/kg/day based
UFH = 10x........... day. on cumulative decreases in body-
FQPA SF = 1x........ weight gains.
Incidental oral short-term--1 to NOAEL= 1.25 mg/kg/ LOC for MOE = < 100 Reproduction and fertility Study
30 days. day. (rat; dietary) Parental/Offspring
UFA = 10x........... LOAEL = 12.5 mg/kg/day based on
UFH = 10x........... decreased pup weight in males on
FQPA SF = 1x........ day 21 and reduction in body-
weight gain of F0 females prior
to mating, gestation and
Inhalation short- and Inhalation (or oral) LOC for MOE = < 100 Reproduction and fertility study
intermediate-term inhalation and study NOAEL = 1.25 (rat; dietary) Parental/Offspring
oral absorption assumed mg/kg/day LOAEL = 12.5 mg/kg/day based on
equivalent. inhalation decreased pup weight in males on
absorption rate = day 21 and reduction in body-
100%. weight gain of F0 females prior
UFA = 10x........... to mating, gestation and
UFH = 10x........... lactation.
FQPA SF = 1x........
Cancer, Oral, dermal, inhalation. Difenoconazole is classified ``Suggestive Evidence of Carcinogenic
Potential'' with a non-linear (MOE) approach for human risk
POD = A data point or an estimated point that is derived from observed dose-response data and used to mark the
beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.
NOAEL = No observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty
factor. 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 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
(i.e., anticipated residues) for the majority of commodities, and the
available empirical or DEEMTM (ver. 7.81) default processing
factors, and 100 PCT.
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.
Cancer risk is 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 noncancer 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 a nonlinear RfD approach is appropriate
for assessing cancer risk difenoconazole. 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 and the cancer
exposure assessment would not exceed the chronic exposure estimate.
Therefore, the chronic dietary risk estimate will be protective of
potential cancer risk.
Cancer risk was assessed using the same exposure estimates as
discussed in Unit III.C.1.ii.
iv. Anticipated residue 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. 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 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 surface water are estimated to be 15.8 parts per
billion (ppb) for acute exposures and 10.4 ppb for chronic exposures.
For ground water, the EDWCs are estimated to be 0.0128 ppb for both
acute and chronic exposures.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. The water concentration of
15.8 ppb and 10.4 ppb were used to assess the contribution to drinking
water in the acute and chronic dietary risk assessments, respectively.
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: Application to ornamentals. There is a potential
for exposure to difenoconazole during mixing, loading, and application
activities through the dermal and inhalation routes. Difenoconazole
products are applied by homeowners using handheld spray equipment.
Exposure duration is considered short-term (1-30 days). In addition,
residential post-application exposure to treated golf course turf is
possible for recreational golfers. 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 (EPA, 2002). With triazole type fungicides
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 reregistration docket at
http://www.regulations.gov, docket 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
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 in body weight gain and decreased in 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 were reduced to 1x. That decision is based on the following
i. The toxicity database for difenoconazole is adequate for
conducting a FQPA risk assessment. At this time, an immunotoxicity
study is not available. However, the toxicology database for
difenoconazole 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 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
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
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. Using the exposure assumptions discussed in this unit
for acute exposure, the acute dietary exposure from food and water to
difenoconazole will occupy 19% of the aPAD for children, 1-2 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 49% of the cPAD for
children 1-2 years old the population group receiving the greatest
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 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 difenoconazole.
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 aggregate MOEs of 260. Because
EPA's level of concern for difenoconazole is a MOE of 100 or below,
these MOEs are not of concern.
4. Aggregate cancer risk for U.S. population. Based on the
discussion in Unit III.A and the toxicological endpoints described in
Unit III.B, EPA has concluded that the cPAD is protective of possible
cancer effects; therefore, given the results of the chronic risk
assessment described in this unit, cancer risk resulting from exposure
to difenoconazole is not of concern.
5. 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 enforcement method, gas chromatography/nitrogen-
phosphorus detection (GC/NPD) method AG-575B, is available for the
determination of residues of difenoconazole per se in/on plant
commodities. An adequate enforcement method, liquid chromatography mass
spectrometry (LC/MS/MS) method REM 147.07b, is available for the
determination of residues of difenoconazole and CGA-205375 in livestock
commodities. Adequate confirmatory methods are also available. This is
the first difenoconazole petition since the new livestock method
(147.07b) was approved by the Agency and this new method has lower
level of quantitation than the previous enforcement method.
The methods 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:
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
Codex maximum residue levels (MRLs) for residues of difenoconazole
per se have been established at 0.2 ppm for carrot; 0.02 ppm for soya
bean (dry); 0.2 ppm for cherries and plums (including prunes); and 0.5
ppm for nectarines and peaches. Canadian and Mexican MRLs have been
established for difenoconazole; however, no MRLs have been established
for the commodities included in the current petition. Codex MRLs for
residues of difenoconazole and its metabolite CGA-205375, expressed as
difenoconazole have been established at 0.2 ppm for edible offal
(mammalian) and 0.01 for eggs. Also, Canadian MRLs have been
established for difenoconazole at 0.05 ppm for meat byproducts of
cattle, goats, hogs, and sheep and at 0.05 ppm in eggs. Based on the
submitted/available magnitude of the residue data, harmonization with
established Codex MRLs is not possible for carrots, soya bean (dry),
cherries, plums (including prunes), nectarines, peaches, edible offal
(mammalian), and eggs because the Codex MRLs are too low, due to
differences in the use patterns, called Good Agricultural Practices or
Harmonization with the established Canadian MRLs for eggs and meat
byproducts of cattle, goats, hogs, and sheep is not possible due to
differences in the regulated residue expression.
C. Response to Comments
One anonymous comment was received on August 7, 2010. This
commenter opposes the establishment of any numerical tolerance other
than zero. No information was submitted to support the commenter's
D. Revisions to Petitioned-For Tolerances
1. Tolerances for carrot, chickpea, and soybean, seed were
corrected to use the recommendation from the EPA tolerance spreadsheet
(January 2008 version).
2. No tolerance proposal was made for soybean, hulls, which is a
regulated commodity. A tolerance is being established for this
commodity, because difenoconazole residues concentrate in this
3. Commodity names for proposed tolerances are being corrected to
be consistent with EPA's standard commodity vocabulary definitions:
``Chickpeas'' to ``Chickpea;'' ``Soybean, aspirated grain fractions''
to ``Aspirated Grain Fractions;'' ``Fruits, stone, group 12'' to
``Fruit, stone, group 12''.
4. The animal commodity tolerance expression is being changed
slightly to express the metabolite CGA 205375 as a difenoconazole
5. There are a number of livestock feedstuffs associated with the
proposed uses and currently established livestock tolerances were
reassessed. Due primarily to the significant change in the beef diet
from the proposed use on soybeans and the residues of difenoconazole
found in/on soybean aspirated grain fractions, the tolerance levels for
residues of concern in liver of cattle, goat, hog, horse, and sheep
need to be increased from 0.20 ppm to 0.40 ppm.
6. Although there was little change in the poultry diet from the
proposed new uses, due to the lower level of quantitation from the new
animal commodity enforcement analytical method (method 147.07b), the
tolerance level for residues of concern in egg needs to be decreased
from 0.10 ppm to 0.02 ppm. Furthermore, the existing commodity name for
``eggs'' is being corrected to ``egg'' consistent with EPA's standard
commodity vocabulary definition.
7. The proposed increased tolerance for milk is not needed because
the calculations for changes in the dietary burden due to the new uses
indicate no change is needed.
Therefore, tolerances are established for residues of
1,3-dioxolan-2-yl]methyl)-1H-1,2,4-triazole, in or on: Aspirated grain
fractions at 95 ppm; carrot at 0.50 ppm; chickpea at 0.08 ppm; fruit,
stone, group 12 at 2.5 ppm; soybean, hulls at 0.20; soybean, seed at
0.15; strawberry at 2.5 ppm; turnip greens at 35 ppm. The existing
animal commodity tolerance expression is being revised, and tolerances
are being increased for liver of cattle/goat/hog/horse/sheep from 0.20
ppm to 0.40 ppm. The existing egg tolerance is being decreased from
0.10 ppm to 0.02 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 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
Dated: June 7, 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 180.475 is amended as follows:
i. In the table to paragraph (a)(1), by alphabetically adding the
following commodities; and
ii. In paragraph (a)(2), by revising the introductory text and the
following commodities in the table.
The amendments read as follows:
Sec. 180.475 Difenoconazole; tolerances for residues.
(a) * * *
(1) * * *
* * * * *
Aspirated grain fractions................................... 95
* * * * *
* * * * *
Fruits, stone, group 12..................................... 2.5
* * * * *
Soybean, hulls.............................................. 0.20
Soybean, seed............................................... 0.15
Turnip, greens.............................................. 35
* * * * *
(2) Tolerances are established for residues of difenoconazole,
including its metabolites and degradates, in the commodities in the
table below. Compliance with the tolerance levels specified below is to
be determined by measuring the sum of difenoconazole, 1-[2-[2-chloro-4-
triazole, and its metabolite, CGA-205375, 1-[2-chloro-4-(4-chloro-
phenoxy)phenyl]-2-[1,2,4]triazol-1-yl-ethanol, calculated as the
stoichiometric equivalent of difenoconazole, in the following
* * * * *
Cattle, liver................................................ 0.40
* * * * *
* * * * *
Goat, liver.................................................. 0.40
* * * * *
Hog, liver................................................... 0.40
* * * * *
Horse, liver................................................. 0.40
* * * * *
Sheep, liver................................................. 0.40
* * * * *
* * * * *
[FR Doc. 2011-14770 Filed 6-14-11; 8:45 am]
BILLING CODE 6560-50-P