Source: https://www.federalregister.gov/documents/2015/04/02/2015-07354/difenoconazole-pesticide-tolerances
Timestamp: 2018-03-24 21:52:10
Document Index: 744337708

Matched Legal Cases: ['art 178', 'art 178', 'art 178', 'art 2', 'art 180', 'art 180', '§\u2009180']

This regulation is effective April 2, 2015. Objections and requests for hearings must be received on or before June 1, 2015, and must be filed in accordance with the instructions provided in 40 CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
80 FR 17697
17697-17703 (7 pages)
EPA-HQ-OPP-2014-0149
FRL-9923-82
2015-07354
Difenoconazole: New Foliar Uses on Pea and Bean, Dried...
Drinking Water Exposure Assessment in support of the new use...
Difenoconazole: Acute and Chronic Aggregate Dietary Exposure...
Company Notice of Filing for Difenoconazole in on Fruit, pome,...
https://www.federalregister.gov/d/2015-07354 https://www.federalregister.gov/d/2015-07354
Start Preamble Start Printed Page 17697
This regulation establishes tolerances for residues of difenoconazole in or on multiple commodities which are identified and discussed later in this document. Syngenta Crop Protection requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2014-0149, is available at http://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 http://www.epa.gov/​dockets.
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-2014-0149 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 June 1, 2015. 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 by docket ID number EPA-HQ-OPP-2014-0149, by one of the following methods:
In the Federal Register of September 5, 2014 (79 FR 53009) (FRL-9914-98), 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 4F8231) by Syngenta Crop Protection, LLC., P.O. Box 18300, Greensboro, NC 27419-8300. The petition requested that 40 CFR part 180 be amended by establishing tolerances for residues of the fungicide, difenoconazole in or on pea, and bean, dried shelled, except soybean, subgroup 6C at 0.2 parts per million (ppm); pea, vine at 10 ppm; pea, hay at 40 ppm; and bushberry, subgroup 13-07B at 3.0 ppm. The petition also requested that the existing tolerance for chickpea be removed. That document referenced a summary of the petition prepared by Syngenta, the registrant, which is available in the docket identified by docket ID number EPA-HQ-OPP-2014-0373, http://www.regulations.gov. Comments were received on the notice of filing. EPA's response to these comments is discussed in Unit IV.C.
In the Federal Register of February 11, 2015 (80 FR 7559) (FRL-9921-94), 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 3F8209) by Syngenta Crop Protection, LLC., P.O. Box 18300, Greensboro, NC 27419-8300. The petition requested that 40 CFR part 180 be amended by increasing existing tolerances for residues of the fungicide, difenoconazole in or on fruit, pome, group 11-10 from 1.0 to 3.0 ppm, and apple, wet pomace from 4.5 to 7.5 ppm. That document referenced a summary of the petition prepared by Syngenta Crop Protection, 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 modified the levels at which some of the tolerances are being established. The reason for these changes are explained in Unit IV.D.Start Printed Page 17698
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 1-day 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 effects-levels (NOAELs). No systemic toxicity was observed at the limit dose in the most recently submitted 28-day rat dermal toxicity study.
EPA is using the non-linear (reference dose) 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 statistically significant carcinomas tumors were only induced at excessively-high doses. Adenomas (benign tumors) and liver necrosis only were seen at 300 parts per million (ppm) (46 and 58 mg/kg/day in males and females, respectively). Based on excessive toxicity observed at the two highest doses in the study, the presence of only benign tumors and necrosis at the mid-dose, 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 no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov on page 44 of the document titled “Difenoconazole: Human Health Risk Assessment for proposed new foliar uses on legume subgroup 6C and bushberry subgroup 13-07B; post-harvest uses on pome fruit group 11-10; and ornamental plants and vegetable transplants grown in both indoor and outdoor production facilities” in docket ID number EPA-HQ-OPP-2014-0149.
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 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 Table 1 of this unit.Start Printed Page 17699
Table 1—Summary of Toxicological Doses and Endpoints for Difenoconazole for Use in Human Health Risk Assessment
Acute dietary (All populations) NOAEL = 25 mg/kg/day UFA = 10x UFH = 10x FQPA SF = 1x Acute RfD = 0.25 mg/kg/day aPAD = 0.25 mg/kg/day Acute neurotoxicity study in rats LOAEL= 200 mg/kg in males based on reduced fore-limb grip strength in males on day 1.
Chronic dietary (All populations) NOAEL= 0.96 mg/kg/day UFA = 10x UFH = 10x FQPA SF = 1x Chronic RfD = 0.01 mg/kg/day cPAD = 0.01 mg/kg/day Combined chronic toxicity/carcinogenicity rat; dietary LOAEL = 24.1/32.8 mg/kg/day (M/F) based on cumulative decreases in body-weight gains.
Dermal Short-term (1-30 days) Oral NOAEL = 1.25 mg/kg/day dermal absorption rate = 6% UFA = 10x UFH = 10x FQPA SF = 1x LOC for MOE = 100 Reproduction and fertility Study rat; dietary Parental/Offspring LOAEL = 12.5 mg/kg/day based on decreased pup weight in males on day 21 and reduction in body-weight gain of F0 females prior to mating, gestation and lactation.
Inhalation short-term (1-30 days) Inhalation and oral absorption assumed equivalent Oral NOAEL = 1.25 mg/kg/day UFA = 10x UFH = 10x FQPA SF = 1x LOC for MOE = 100 Reproduction and fertility Study rat; dietary Parental/Offspring LOAEL = 12.5 mg/kg/day based on decreased pup weight in males on day 21 and reduction in body-weight gain of F0 females prior to mating, gestation and lactation.
Cancer (oral, dermal, inhalation) The Agency is using a non-linear approach based on the chronic POD to assess the carcinogenic potential of difenoconazole.
Such effects were identified for difenoconazole. In estimating acute dietary exposure, EPA used 2003-2008 food consumption information from the United States Department of Agriculture's (USDA) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). As to residue levels in food, EPA assumed tolerance level residues and 100 percent crop treated (PCT) information.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA's NHANES/WWEIA. As to residue levels in food, EPA used USDA Pesticide Data Program (PDP) monitoring data, average field trial residues for some commodities, tolerance level residues for the remaining commodities, and average percent crop treated for some commodities.
For the chronic dietary exposure analysis, the Agency estimated the PCT for existing uses as follows:
Almond 5%, cabbage 2.5%, cucumbers 5%, garlic 5%, grape 5%, grapefruit 2.5%, onions 5%, orange 2.5%, pecan 2.5%, peach 1%, peppers Start Printed Page 177002.5%, pistachio 2.5%, pumpkin 2.5%, squash 5%, strawberry 2.5%, sugar beets 15%, tangerine 2.5%, tomatoes 25%, walnut 2.5%, watermelon 5%, and wheat 10%.
The drinking water assessment was performed using a total toxic residue (TTR) method which considers both parent difenoconazole and its major metabolite, CGA-205375, in surface and groundwater.
Based on the surface water concentration calculator (SWCC) and screening concentration in ground water (SCI-GROW) and pesticide root zone model ground water (PRZM GW) models, the estimated drinking water concentrations (EDWCs) of difenoconazole for acute exposures are estimated to be 20.0 parts per billion (ppb) for surface water and 1.77 ppb for ground water and for chronic exposure assessments are estimated to be 13.6 ppb for surface water and not detected 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 20.0 ppb was used to assess the contribution to drinking water. For chronic dietary risk assessment, the water concentration of value 13.6 ppb was used to assess the contribution to drinking water.
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 use on ornamentals (garden/trees). For residential post-application, short-term dermal exposure is expected for both adults and children from post-application activities in treated gardens.
The scenarios used in the aggregate assessment were those that resulted in the highest exposures. The highest exposures consist of the following:
Short-term dermal exposure to adults from post-application activities in treated gardens, and
Short-term dermal exposure to children (6-11 years old) from post-application activities in treated gardens.
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). 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 propiconazole, 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 Start Printed Page 17701assessment 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.
The most recent update for the triazoles was conducted on October 24, 2013. The requested new uses of difenoconazole did not significantly change the dietary exposure estimates for free triazole or conjugated triazoles. Therefore, an updated dietary exposure analysis was not conducted. The October 24, 2013 update for triazoles may be found in docket ID number EPA-HQ-OPP-2014-0149.
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). 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.
iv. There are no residual uncertainties identified in the exposure databases. The dietary risk assessment is conservative, using tolerance level residues and 100 PCT for the acute assessment while the chronic assessment used 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. These assessments will not underestimate the exposure and risks posed by difenoconazole.
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 49% of the aPAD for all infants less than 1 year 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 88% of the cPAD for children 1-2 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.
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 170 for adults and 190 for children. Because EPA's level of concern for difenoconazole is a MOE of 100 or below, these MOEs are not of concern.
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 Start Printed Page 17702at 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.
An adequate enforcement method, 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/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.
The Codex has an established MRL for the sum of difenoconazole and its metabolite, 1-[2-chloro-4-(4-chlorophenoxy)-phenyl]-2-(1,2,4-triazol)-1-yl-ethano), expressed as difenoconazole in or on milk at 0.02 ppm, which is the same as the recommended U.S. tolerance.
The Codex has not established an MRL for difenoconazole in or on pea and bean, dried shelled, except soybean, subgroup 6C; bushberry subgroup 13-07B; pea, field, hay; pea, field, vines; or apple, wet pomace.
The Codex has an established MRL for difenoconazole in or on pome fruit at 0.5 ppm for residues incurred from foliar uses of difenoconazole. This MRL differs from the recommended U.S. tolerance for difenoconazole in or on fruit, pome, group 11-10 at 5.0 ppm. The Codex MRL is not adequate to cover residues incurred from the proposed post-harvest uses in the United States; therefore, harmonization with Codex is not possible at this time.
Several comments were received in response to the notice of filing, however, all were concerned with effects to bees and related to other petitions and chemicals contained in the same notice of filing, not difenoconazole.
The tolerance being established for the bushberry subgroup 13-07B is 4.0 ppm, not 3.0 ppm as proposed. This is due to the independent field trial determination which resulted in the exclusion of one of the trials from the Organization for Economic Cooperation and Development (OECD) tolerance calculation procedures. The tolerance being established for the pea and bean, dried shelled, except soybean, subgroup 6C tolerance is being set at 0.20 ppm, not 0.2 ppm, and is based on the current practice of setting tolerances to 2 significant figures. The established tolerance in milk is being increased from 0.01 ppm to 0.02 ppm because of the new pea hay and vine feedstuffs which significantly increased the maximum reasonably balanced dietary estimate for dairy cattle. Furthermore, the Agency is establishing tolerances for the fruit, pome, group 11-10 and apple, wet pomace (5.0 ppm and 25 ppm, respectively) at higher levels than requested (3.0 ppm and 7.5 ppm, respectively). The established tolerances for fruit, pome, group 11-10 take into account maximum tolerance estimates that may result from post-harvest application techniques for pome fruit. The established tolerances for apple, wet pomace was calculated based on the highest average field trial residues in or on apples and the average processing factor for wet pomace. Lastly, some commodity terms were modified to be consistent with Agency's preferred food and feed commodity vocabulary.
Therefore, tolerances are established for residues of difenoconazole, in or on bushberry subgroup 13-07B at 4.0 ppm; pea and bean, dried shelled, except soybean, subgroup 6C at 0.20 ppm; pea, field, hay at 40 ppm; and pea, field, vines at 10 ppm. Additionally, existing tolerances are modified as follows: Apple, wet pomace from 7.5 ppm to 25 ppm; fruit, pome, group 11-10 from 3.0 to 5.0 ppm; and milk from 0.01 to 0.02 ppm. Lastly, the existing chickpea tolerance is removed as unnecessary since it is now covered by the pea and bean, dried shelled, except soybean, subgroup 6C tolerance.
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 Start Printed Page 17703Flexibility Act (RFA) (5 U.S.C. 601 et seq.), do not apply.
2. In § 180.475:
i. Remove “Chickpea” from the table in paragraph (a)(1).
ii. Add alphabetically the entries for “Bushberry subgroup 13-07B”, “Pea and bean, dried shelled, except soybean, subgroup 6C”, “Pea, field, hay”, and “Pea, field, vines” to the table in paragraph (a)(1).
iii. Revise the entries for “Apple, wet pomace” and “Fruit, pome, group 11-10” in the table in paragraph (a)(1).
iv. Revise the entry for “Milk” in the table in paragraph (a)(2).
Apple, wet pomace 25
Fruit, pome, group 11-10 5.0
Pea and bean, dried shelled, except soybean, subgroup 6C 0.20
[FR Doc. 2015-07354 Filed 4-1-15; 8:45 am]