Difenoconazole; Pesticide Tolerances, 3615-3622 [2018-01479]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 83, Number 18 (Friday, January 26, 2018)]
[Rules and Regulations]
[Pages 3615-3622]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-01479]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2016-0254; FRL-9971-95]


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 multiple commodities which are identified and 
discussed later in this document. In addition, this regulation removes 
several previously established tolerances that are superseded by this 
final rule. Interregional Research Project Number 4 (IR-4) requested 
these tolerances under the Federal Food, Drug, and Cosmetic Act 
(FFDCA).

DATES: This regulation is effective January 26, 2018. Objections and 
requests for hearings must be received on or before March 27, 2018, 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: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2016-0254, is available at https://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 
1301 Constitution Ave. NW, Washington, DC 20460-0001. The Public 
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through 
Friday, excluding legal holidays. The telephone number for the Public 
Reading Room is (202) 566-1744, and the telephone number for the OPP 
Docket is (703) 305-5805. Please review the visitor instructions and 
additional information about the docket available at https://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Michael Goodis, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW, Washington, DC 20460-0001; telephone number: 
(703) 305-7090; email address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

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 https://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

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-2016-0254 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 
March 27, 2018. 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 (excluding any Confidential Business Information (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 the non-CBI copy of your objection or hearing 
request, identified

[[Page 3616]]

by docket ID number EPA-HQ-OPP-2016-0254, by one of the following 
methods:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW, Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at https://www.epa.gov/dockets/contacts.html. Additional 
instructions on commenting or visiting the docket, along with more 
information about dockets generally, is available at https://www.epa.gov/dockets.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of July 26, 2017 (82 FR 34664) (FRL-9963-
50), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
6E8484) by IR-4 Headquarters, Rutgers, The State University of New 
Jersey, 500 College Road East, Suite 201W, Princeton, NJ 08540. 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-methy-1,3-dioxolan-2-ylmethyl]-1H-
1,2,4-triazole, in or on Brassica, leafy greens, subgroup 4-16B at 35 
parts per million (ppm); cranberry at 0.6 ppm; fruit, small, vine 
climbing, except fuzzy kiwifruit, subgroup 13-07F at 4.0 ppm; guava at 
3.0 ppm; kohlrabi at 2.0 ppm; papaya at 0.6 ppm; and vegetable, 
Brassica, head and stem, group 5-16 at 2.0 ppm. Upon establishment of 
proposed tolerances above, the petition requested that 40 CFR part 
180.475 be amended by removing existing tolerances for residues of 
difenoconazole in or on Brassica, head and stem, subgroup 5A at 1.9 
ppm, Brassica, leafy greens, subgroup 5B at 35 ppm; grape at 4.0 ppm; 
and turnip, greens at 35 ppm. That document referenced a summary of the 
petition prepared by Syngenta Crop Protection, the registrant, which is 
available in the docket, https://www.regulations.gov. There were no 
comments received in response to the notice of filing.
    Tolerances being established vary from what was requested, for the 
reasons 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 FFDCA section 408(b)(2)(D), and the factors 
specified in FFDCA section 408(b)(2)(D), 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 exhibits 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 toxicity studies with 
difenoconazole in mice and rats showed decreased body weights and 
effects on the liver (e.g. hepatocellular hypertrophy, liver necrosis, 
fatty changes in the liver). No systemic toxicity was observed at the 
limit dose in a rat dermal toxicity study.
    The available toxicity studies indicated no increased 
susceptibility of rats or rabbits from in utero or postnatal exposure 
to difenoconazole. In prenatal developmental toxicity studies in rats 
and rabbits and in the 2-generation reproduction study in rats, fetal 
and offspring toxicity, when observed, occurred at equivalent or higher 
doses than in the maternal and parental animals. In a rat developmental 
toxicity study, developmental effects were observed at doses higher 
than those which caused maternal toxicity. Developmental effects in the 
rat included increased incidence of ossification of the thoracic 
vertebrae and thyroid, decreased number of sternal centers of 
ossification, increased number of ribs and thoracic vertebrae, and 
decreased number of lumbar vertebrae. In the rabbit study, 
developmental effects (increases in post-implantation loss and 
resorptions and decreases in fetal body weight) were also seen at 
maternally toxic (decreased body weight gain and food consumption) 
doses. Since the developmental effects are more severe than the 
maternal effects, qualitative susceptibility is indicated in the rabbit 
developmental study; however, the selected POD is protective of this 
effect. In the 2-generation reproduction study in rats, toxicity to the 
fetuses and offspring, when observed, occurred at equivalent or higher 
doses than in the maternal and parental animals.
    In an acute neurotoxicity study in rats, reduced fore-limb grip 
strength was observed on day one in males at the lowest-observed-
adverse-effect-level of 200 mg/kg (LOAEL), and clinical signs of 
neurotoxicity were observed in females only at the highest dose tested 
(2,000 mg/kg). In a subchronic neurotoxicity study in rats, decreased 
hind limb strength was observed in males only at doses >=17.5 mg/kg/
day. The effects observed in acute and subchronic neurotoxicity studies 
are transient with no histologic findings.
    Although there is some evidence that difenoconazole affects 
antibody levels at doses that cause systemic 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. Difenoconazole is not mutagenic, and no evidence of 
carcinogenicity was seen in rats. Evidence for carcinogenicity was seen 
in mice as induction of liver tumors at doses which were considered to 
be excessively high for carcinogenicity testing. Difenoconazole has 
been classified as ``Suggestive Evidence of Carcinogenic Potential'' 
based on liver tumors observed in mice at 46.3 mg/kg/day and higher, 
the absence of tumors at two lower doses of 1.5 and 4.6 mg/kg/day, 
respectively, excessive toxicity

[[Page 3617]]

observed at the two highest doses of 423 and 819 mg/kg/day, 
respectively, the absence of genotoxicity, and no evidence of 
carcinogenicity in rats. EPA has concluded that the chronic point of 
departure (POD) for assessing chronic risk (0.96 mg/kg/day) will be 
protective of any cancer effects for the following reasons: (1) Tumors 
were seen in only one species; (2) carcinoma tumors were observed only 
at the two highest doses (2,500 and 4,500 ppm) in the mouse 
carcinogenicity study; (3) benign tumors and necrosis were observed at 
the mid- dose (300 ppm) ; (4) the absence of tumors at the study's 
lower doses (30 ppm); (5) the absence of genotoxic or mutagenic 
effects. The cRfD of 0.96 mg/kg/day is well below the no-observed- 
adverse-effect-level (NOAEL) of the mouse carcinogenicity study of 30 
ppm (4.7 and 5.6 mg/kg/day in males and females, respectively), at 
which no effects on the biological endpoints relevant to tumor 
development (i.e., hepatocellular hypertrophy, liver necrosis, fatty 
changes in the liver and bile stasis) were seen. As a result, EPA has 
concluded that a nonlinear RfD approach is appropriate for assessing 
cancer risk to difenoconazole and a separate quantitative cancer 
exposure assessment is unnecessary.
    Specific information on the studies received and the nature of the 
adverse effects caused by difenoconazole 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 https://www.regulations.gov in document ``SUBJECT: Difenoconazole. Human Health 
Risk Assessment for Proposed New Foliar Uses on Cranberry, Guava, and 
Papaya. Expansion of Registered Foliar Use on Grape to Crop Subgroup 
13-07F (Fruit, Small, Vine Climbing, Except Fuzzy Kiwifruit). 
Conversion of Registered Foliar Uses on Crop Subgroups 5A and 5B to 
Crop Group 5-16 (Vegetable, Brassica, Head and Stem), Crop Subgroup 4-
16B (Brassica, Leafy Greens (includes Watercress)), and Kohlrabi, 
October 11, 2017'' at pp. 42-50 in docket ID number EPA-HQ-OPP-2016-
0254.

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 https://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/assessing-human-health-risk-pesticides.
    A summary of the toxicological endpoints for difenoconazole used 
for human risk assessment is discussed in Unit III.B. of the final rule 
published in the Federal Register of April 2, 2015 (80 FR 17697) (FRL-
9923-82).

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 Dietary Exposure Evaluation Model 
software with the Food Commodity Intake Database DEEM-FCID which 
incorporates consumption data from the United States Department of 
Agriculture's (USDA) National Health and Nutrition Examination Survey, 
What We Eat in America, (NHANES/WWEIA) conducted from 2003 to 2008. As 
to residue levels in food, EPA assumed tolerance-level residues, 100 
percent crop treated (PCT), and available empirical or DEEM (ver. 7.81) 
default processing factors.
    ii. Chronic exposure. In conducting a refined chronic dietary 
exposure assessment EPA used the food consumption data from USDA's 
NHANES/WWEIA survey program. As to residue levels in food, EPA assumed 
tolerance-level residues for some commodities, average field trial 
residues and USDA Pesticide Data Program monitoring samples for the 
remaining commodities, available empirical or DEEM (ver.7.81) default 
processing factors, and average PCT assumptions for some commodities.
    iii. Cancer. Based on the data summarized in Unit III.A., EPA has 
concluded that a nonlinear RfD approach is appropriate for assessing 
cancer risk to difenoconazole. Therefore, a separate quantitative 
cancer exposure assessment is unnecessary since the chronic dietary 
risk estimate will be protective of potential cancer risk.
    iv. Anticipated residue and PCT information. 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.
    Section 408(b)(2)(F) of FFDCA states that the Agency may use data 
on the actual percent of food treated for assessing chronic dietary 
risk only if:
     Condition a: The data used are reliable and provide a 
valid basis to show what percentage of the food derived from such crop 
is likely to contain the pesticide residue.
     Condition b: The exposure estimate does not underestimate 
exposure for any significant subpopulation group.
     Condition c: Data are available on pesticide use and food 
consumption in a particular area, the exposure estimate does not 
understate exposure for the population in such area.
    In addition, the Agency must provide for periodic evaluation of any 
estimates used. To provide for the periodic evaluation of the estimate 
of PCT as required by FFDCA section 408(b)(2)(F), EPA may require 
registrants to submit data on PCT.
    For the chronic dietary exposure analysis, the Agency used average 
PCT

[[Page 3618]]

estimates for existing uses as follows: Almond 10%, apple 20%, apricot 
10%, broccoli 2.5%, Brussels sprout 2.5%, cabbage 5%, cantaloupe 2.5%, 
carrot 5%, cauliflower 2.5%, cherry 2.5%, cucumber 5%, garlic 5%, grape 
10%, grapefruit 5%, hazelnut 1%, nectarine 2.5%, onion 5%, orange 2.5%, 
pecan 2.5%, peach 2.5%, pear 10%, pepper 5%, pistachio 5%, plum 10%, 
potato 20%, pumpkin 2.5%, soybean 2.5%, squash 5%, strawberry 2.5%, 
sugar beet 15%, tangerine 2.5%, tomato 25%, walnut 1%, watermelon 5%, 
and wheat 10%.
    In most cases, EPA uses available data from United States 
Department of Agriculture/National Agricultural Statistics Service 
(USDA/NASS), proprietary market surveys, and the National Pesticide Use 
Database for the chemical/crop combination for the most recent 6-7 
years. EPA uses an average PCT value for chronic dietary risk analysis. 
The average PCT value for each existing use is derived by combining 
available public and private market survey data for that use and 
averaged across all observations and is rounded up to the nearest 
multiple of 5%, for use in the analysis unless the average PCT value is 
estimated at less than 2.5% or 1%, in which case the Agency uses 2.5% 
or 1%, respectively, as the average PCT value in the analysis. EPA uses 
a maximum PCT value for acute dietary risk analysis. The maximum PCT 
value is the highest observed maximum value reported within the recent 
6 years of available public and private market survey data for the 
existing use and rounded up to the nearest multiple of 5% for use in 
the analysis, unless the maximum PCT value is estimated at less than 
2.5%, in which case the Agency uses 2.5% as the maximum PCT value in 
the analysis.
    The Agency believes that the three conditions discussed in Unit 
III.C.1.iv. have been met. With respect to Condition a, PCT estimates 
are derived from Federal and private market survey data, which are 
reliable and have a valid basis. The Agency is reasonably certain that 
the percentage of the food treated is not likely to be an 
underestimation. As to Conditions b and c, regional consumption 
information and consumption information for significant subpopulations 
is taken into account through EPA's computer-based model for evaluating 
the exposure of significant subpopulations including several regional 
groups. Use of this consumption information in EPA's risk assessment 
process ensures that EPA's exposure estimate does not understate 
exposure for any significant subpopulation group and allows the Agency 
to be reasonably certain that no regional population is exposed to 
residue levels higher than those estimated by the Agency. Other than 
the data available through national food consumption surveys, EPA does 
not have available reliable information on the regional consumption of 
food to which difenoconazole may be applied in a particular area.
    2. Dietary exposure from drinking water. The drinking water 
assessment was performed using a total toxic residue method, which 
considers both parent difenoconazole and its major metabolite, CGA 
205375, or total toxic residues (TTR) from difenoconazole uses, in 
surface and groundwater. The Agency used screening level water exposure 
models in the dietary exposure analysis and risk assessment for 
difenoconazole and CGA 205375 in drinking water. These simulation 
models take into account data on the physical, chemical, and fate/
transport characteristics of difenoconazole, plus CGA 205375. Further 
information regarding EPA drinking water models used in pesticide 
exposure assessment can be found at https://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/about-water-exposure-models-used-pesticide.
    Based on the Tier II Pesticide in Water Calculator (PWC v1.52) 
model and Tier 1 Rice Model, the estimated drinking water 
concentrations (EDWCs) of TTR of difenoconazole for acute exposures are 
estimated to be 33.4 parts per billion (ppb) for surface water and 2.0 
ppb for ground water. For chronic exposures EDWCs of TTR of 
difenoconazole for non-cancer assessments are estimated to be 27.8 ppb 
for surface water and 0.60 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 33.4 ppb was used to 
assess the contribution to drinking water. For chronic dietary risk 
assessment, the water concentration value of 27.8 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: Treatment of ornamental plants 
in commercial and residential landscapes and interior plantscapes. EPA 
assessed residential exposure using the following assumptions: For 
residential handlers, adult short-term dermal and inhalation exposure 
is expected from mixing, loading, and applying difenoconazole on 
ornamentals (gardens and trees). For residential post-application 
exposures, short-term dermal exposure is expected for both adults and 
children from post-application activities in treated residential 
landscapes.
    The scenarios used in the aggregate assessment were those that 
resulted in the highest exposures. The highest exposures consist of the 
short-term dermal exposure to adults from post-application activities 
in treated gardens and short-term dermal exposure to children 6 to 11 
years old from post-application activities in treated gardens. Further 
information regarding EPA standard assumptions and generic inputs for 
residential exposures may be found at https://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide.
    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 conazole class of fungicides 
containing the 1,2,4-triazole moiety. 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).
    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 difenoconazole shares a 
common mechanism of toxicity with any other conazole pesticide, and

[[Page 3619]]

EPA is not following a cumulative risk approach for this tolerance 
action. For information regarding EPA's procedures for cumulating 
effects from substances found to have a common mechanism of toxicity, 
see EPA's website at https://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.
    Difenoconazole is a triazole-derived pesticide. This class of 
compounds can form the common metabolite 1,2,4-triazole and two 
conjugated triazole metabolites (triazolylalanine and triazolylacetic 
acid). To support existing tolerances and to establish new tolerances 
for triazole-containing pesticides, including difenoconazole, EPA 
previously conducted a human health risk assessment for exposure to 
1,2,4-triazole, triazolylalanine, and triazolylacetic acid resulting 
from existing and pending uses of any triazole-containing 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). The Agency retained a 3X 
for the LOAEL to NOAEL safety factor when the reproduction study was 
used. In addition, the Agency retained a 10X for the lack of studies 
including a developmental neurotoxicity (DNT) study. 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 
https://www.regulations.gov, docket ID number EPA-HQ-OPP-2005-0497.
    The Agency's latest updated aggregate risk assessment for the 
triazole-containing metabolites was finalized on July 18, 2017 and 
includes the new uses in this rule. It is titled, ``Common Triazole 
Metabolites: Updated Aggregate Human Health Risk Assessment to Address 
the New Section 3 Registrations for Use of Difenoconazole and 
Tetraconazole.'' Aggregate risk estimates associated with 1,2,4-
triazole (T) and the conjugated triazole metabolites (i.e., combined 
residues of triazolylalanine (TA) and triazolylacetic acid (TAA)), are 
below the Agency's level of concern. There are no human health risk 
issues for these metabolites that would preclude the new uses of 
difenoconazole. The assessment may be found at https://www.regulations.gov in docket ID number EPA-HQ-OPP-2016-0254.

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. The prenatal and postnatal 
toxicology database for difenoconazole includes rat and rabbit prenatal 
developmental toxicity studies and a 2-generation reproduction toxicity 
study in rats. The available Agency guideline studies indicated no 
increased qualitative or quantitative susceptibility of rats 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 a rat developmental toxicity study developmental 
effects were observed at doses higher than those which caused maternal 
toxicity. In the rabbit study, developmental effects (increases in 
post-implantation loss and resorptions and decreases in fetal body 
weight) were also seen at maternally toxic doses (decreased body weight 
gain and food consumption). Since the developmental effects are more 
severe than the maternal effects, qualitative susceptibility is 
indicated in the rabbit developmental study; however, the selected POD 
is protective of this effect. In 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.
    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 difenoconazole is complete.
    ii. There are no clear signs of neurotoxicity following acute, 
subchronic or chronic dosing in multiple species in the difenoconazole 
database. The effects observed in acute and subchronic neurotoxicity 
studies are transient and showed in one sex (males as reduced fore-limb 
grip strength with no histologic findings), and the selected endpoints 
of toxicity for risk assessment are protective of any potential 
neurotoxicity. Based on the toxicity profile, and lack of concern for 
neurotoxicity, there is no need for a developmental neurotoxicity study 
or additional uncertainty factors (UFs) to account for neurotoxicity.
    iii. There is no evidence that difenoconazole results in increased 
susceptibility in in utero rats or rabbits in the prenatal 
developmental studies or in young rats in the 2-generation reproduction 
study. The qualitative susceptibility seen in the rabbit developmental 
study is adequately protected by the selected POD.
    iv. There are no residual uncertainties identified in the exposure 
databases. The dietary risk assessment utilized tolerance-level 
residues and 100 PCT for the acute assessment; a refined chronic 
assessment incorporated USDA PDP monitoring data, average field-trial 
residues for some commodities, tolerance-level residues for remaining 
commodities, and average PCT for some commodities. These assumptions 
will not underestimate dietary exposure to difenoconazole. EPA made 
conservative (protective) assumptions in the ground and surface water 
modeling used to assess exposure to difenoconazole in drinking water. 
EPA used similarly conservative assumptions to assess post application 
exposure of children as well as incidental oral exposure of toddlers. 
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.
    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 52% of the aPAD for all infants <1 year 
old, the

[[Page 3620]]

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 51% of the cPAD for all 
infants <1year 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 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 aggregate MOEs of 
250 for children and 180 for adults. Because EPA's level of concern for 
difenoconazole is a MOE of 100 or below, these MOEs 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. Based on the data 
summarized in Unit III.A., the chronic dietary risk assessment is 
protective of any potential cancer effects. Based on the results of 
that assessment, EPA concludes that difenoconazole is not expected to 
pose a cancer risk to humans.
    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

    Adequate enforcement methodologies are available to enforce the 
tolerance expression. An adequate enforcement method, gas 
chromatography with 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, GC/MSD 
method AG-676A, is also available for the determination of residues of 
difenoconazole per se in/on canola and barley commodities. A 
confirmatory method, GC/MSD method AG-676, is also available. The Limit 
of Quantitation (LOQs) are 0.01-0.05 ppm.
    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; email address: 
[email protected].

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint United Nations 
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 MRLs for difenoconazole in/on papaya at 
0.2 ppm; grape at 3 ppm (a crop member of fruit, small, vine climbing, 
except fuzzy kiwifruit crop subgroup 13-07F); dried grapes at 6 ppm; 
and broccoli, Brussels sprouts, cabbage and cauliflower at 2 ppm (crop 
members of vegetables, Brassica, head and stem crop group 5-16). The 
U.S. tolerances are harmonized with these Codex MRLs with the exception 
of the U.S. tolerance at 0.60 ppm in/on papaya due to differences in 
U.S. good agricultural practices (GAP) and concerns that the Codex MRL 
in/on papaya at 0.2 ppm is too low to cover residues in/on U.S. papaya 
commodities treated in accordance with approved label directions for 
difenoconazole.

C. Revisions to Petitioned-for Tolerances

    EPA is establishing the tolerance for Fruit, small, vine climbing, 
except fuzzy kiwifruit, subgroup 13-07F at 3.0 ppm rather than the 
requested 4.0 ppm for harmonization with the currently established 
Codex MRL for residues of difenoconazole in/on grape which reflects 
U.S. GAP. In addition, EPA corrected the tolerance level to include an 
additional significant figure for cranberry and papaya from the 
requested 0.6 ppm to 0.60 ppm. This is to avoid the situation where 
rounding of an observed residue to the level of precision of the 
tolerance expression would be considered non-violative (such as 0.64 
ppm being rounded to 0.6 ppm).

V. Conclusion

    Therefore, tolerances are established for residues of the fungicide 
difenoconazole, 1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methy-1,3-
dioxolan-2-ylmethyl]-1H-1,2,4-triazole, in or on Brassica, leafy 
greens, subgroup 4-16B at 35 ppm; Cranberry at 0.60 ppm; Fruit, small, 
vine climbing, except fuzzy kiwifruit, subgroup 13-07F at 3.0 ppm; 
Guava at 3.0 ppm; Kohlrabi at 2.0 ppm; Papaya at 0.60 ppm; and 
Vegetable, Brassica, head and stem, group 5-16 at 2.0 ppm. In addition, 
established tolerances for ``Brassica, head and stem, subgroup 5A''; 
``Brassica, leafy greens, subgroup 5B''; ``Grape''; ``Papaya''; and 
``Turnip, greens'' are removed because they are superseded by the 
tolerances being established in this action.

VI. Statutory and Executive Order Reviews

    This action establishes tolerances under FFDCA section 408(d) 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 action has been 
exempted from review under Executive Order 12866, this action is not 
subject to Executive Order 13211, entitled ``Actions Concerning

[[Page 3621]]

Regulations That Significantly Affect Energy Supply, Distribution, or 
Use'' (66 FR 28355, May 22, 2001); Executive Order 13045, entitled 
``Protection of Children from Environmental Health Risks and Safety 
Risks'' (62 FR 19885, April 23, 1997); or Executive Order 13771, 
entitled ``Reducing Regulations and Controlling Regulatory Costs'' (82 
FR 9339, February 3, 2017). This action 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 FFDCA section 408(d), 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 action 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 FFDCA section 408(n)(4). 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 action. In addition, this 
action does not impose any enforceable duty or contain any unfunded 
mandate as described under Title II of the Unfunded Mandates Reform Act 
(UMRA) (2 U.S.C. 1501 et seq.).
    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 (NTTAA) (15 U.S.C. 272 note).

VII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
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 
the rule in the Federal Register. This action 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: December 27, 2017.
Daniel 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. In Sec.  180.475, paragraph (a)(1):
0
a. Remove the entries for ``Brassica, head and stem, subgroup 5A'' and 
``Brassica, leafy green, subgroup 5B'';
0
b. Add alphabetically the entry for ``Brassica, leafy greens, subgroup 
4-16B'';
0
c. Add alphabetically the entries for ``Cranberry'' and ``Fruit, small, 
vine climbing, except fuzzy kiwifruit, subgroup 13-07F'';
0
d. Remove the entry for ``Grape'';
0
e. Add alphabetically the entries for ``Guava'' and ``Kohlrabi'';
0
f. Revise the entry for ``Papaya'';
0
g. Remove the entry for ``Turnip, greens''; and
0
h. Add alphabetically the entry for ``Vegetable, Brassica, head and 
stem, group 5-16''.
    The additions and revision read as follows:


Sec.  180.475   Difenoconazole; tolerances for residues.

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

------------------------------------------------------------------------
                                                             Parts per
                        Commodity                             million
------------------------------------------------------------------------
 
                              * * * * * * *
Brassica, leafy greens, subgroup 4-16B..................              35
 
                              * * * * * * *
Cranberry...............................................            0.60
 
                              * * * * * * *
Fruit, small, vine climbing, except fuzzy kiwifruit,                 3.0
 subgroup 13-07F........................................
 
                              * * * * * * *
Guava...................................................             3.0
Kohlrabi................................................             2.0
 
                              * * * * * * *
Papaya..................................................            0.60
 
                              * * * * * * *
Vegetable, Brassica, head and stem, group 5-16..........             2.0
 
                              * * * * * * *
------------------------------------------------------------------------


[[Page 3622]]

* * * * *
[FR Doc. 2018-01479 Filed 1-25-18; 8:45 am]
 BILLING CODE 6560-50-P