EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER ( 11 /19/20 10 ) EPA Registration Division contact: [Shaja Joyner (PM - 20) 703 - 308 - 3194]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases where the outline element does not apply, please insert “NA- Remove” and maintain the outline. Please do not change the margins, font, or format in your pestic ide petition. Simply replace the instructions that appear in green and brackets, i.e., “ [ insert company name ] ,” with the information specific to your action. TEMPLATE: [Syngenta Crop Protection] [Insert petition number] EPA has received a pesticide petition ( [insert petition number] ) from [Syngenta Crop Protection] , [P. O. Box 18300, Greensboro, NC 27409] proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 .532

. (Options (pick one) 1. by amending the tolerance for residues of [cyprodinil: 2 - Pyrimidinamine, 4 - cyclopropyl - 6 - methyl - N - phenyl - ] in or on the raw agricultural commodity [] at [] Nut , Tree , Group 1 4 , at 0.10 part per million (ppm) Almond, hulls, at 18.0 part per million Upon approval of the aforementioned tolerances, it is proposed that 40 CFR 180.532 be amended to remove the established tolerances for the residues of cy prodinil in or on the raw agricultural commodity : Almond, at 0.02 part per million Pistachio, at 0.10 part per million EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not full y evaluated the sufficiency

of the submitted dat a at this time or whether the data supports granting of the2

petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism. The metabolism of cyprodinil is adequately understood for the purpose of the proposed tolerances. The metabolism of cyprodinil has been characterized in plants and animals. No toxicologically significant metabolites have been identified. The metabolism profile supports the use of an analytical enforcement method that accounts for only parent cyprodinil. 2. Analytical method. Syngenta Crop Protection has developed and validated analytical methodology for enforcement purposes. This method (Syngenta Crop Protection Method AG- 631B) has passed an Agency petition method validation for several commodities and is currently the enforcement method for cyprodinil. An extensive database of method validation data using this method on various crop commodities is available. 3. Magnitude of residues. Complete residue data to support the requested tolerances have been submitted. The requested tolerances are adequate ly supported. In support o f the requested tolerance, ten crop - field trials were conducted in accordance with the requirements of the EPA Residue Chemistry Guidelines 860.1500 to determine the magnitude of residue of cyprodinil in or on tree nuts. Cyprodi nil was applied in four applications at a rate of 0.5 lb cyprodinil/A per application with a retreatment interval of 14 days. The raw agricultural commodities of tree nuts, i.e., almond hulls, almond nutmeat, and pecan nutmeat, were harvested at typical c ommercial maturity, which approximated a pre - harvest interval (PHI) of 14 days. Site Selection and number of trials were determined to satisfy the requirements listed in OPPTS 860.1500, Crop Field Trials

– Required Number of Field Trials for Crop Groups a nd

– Suggested Distribution of Field Trials by Region for Crops. Pecan trials were conducted accordingly - 2 trials located in Region 2, 1 trial in Region 4, 1 trial in Region 6, 1 trial in Region 8, and for almonds 5 trials were conducted in Region 10 . Trial parameters included concentrate and dilute cover sprays, simulation of aerial application, the use of an adjuvant, and residue decline. Tree nut samples were collected 14 day s after application. The highest averaged field trial residue (HAFT) leve l of cyprodinil resulting from a seasonal rate of 2.0 lb cyprodinil/A was 9.5 ppm in almond hulls, 0.044 ppm in almond nutmeat, and 0.015 ppm in pecan nutmeat for a 14 day PHI. In the current study, samples of almond hulls, almond nutmeat, and pecan nutme at were stored frozen from sampling to extraction for a maximum of 10 months. A storage stability study was conducted to determine the stability of cyprodinil (CGA219417) in or on almond hulls and nutmeat fortified at 1.0 mg/kg and stored frozen at - 20oC ± 10 oC.3

B. Toxicological Profile An assessment of toxic effects caused by cyp rodinil is discussed in Unit III.A. and Unit III.B. of the Federal Register dated June 22, 2001 (66 FR 33478) (FRL - 6778 - 7). The technical cyprodinil product is classified in toxicity categories III & IV [CAUTION] based on acute oral, dermal, inhalatio n toxicity and eye/skin irritation studies. The formulated end use products are also classified in toxicity categories III & IV [CAUTION] based on similar studies. 1. Acute toxicity. The acute toxicity data of cyprodinil show that this chemical is not acutely toxic by the oral, inhalation and dermal routes of exposure. Technical cyprodinil, however, is a dermal sensitizer. 2. Genotoxicty. Cyprod inil was shown to be negative in studies for point mutation, for chromosome aberration, and for DNA repair. These results indicate that cyprodinil is unlikely to initiate cancer or cause inheritable genetic defects. 3. Reproductive and developmental toxicity . Reproductive Toxicity: In a two generation reproduction study in rats, the NOEL for maternal systemic toxicity is 1000 ppm and the NOEL for reproductive toxicity is 1000 ppm. Developmental Toxicity: Cyprodinil is not teratogenic. In the rabbit developmental toxicity study, no developmental toxicity was noted even at the highest dose tested (HDT) of 400 mg/k. In the r at developmental toxicity study , the developmental and maternal NOELs were both 200 mg/kg based on reduced ossification and body w eight in pups and decreased food consumption/weight gain in dams at 1000 mg/kg (HDT). 4. Subchronic toxicity. Subchronic Oral Toxicity: In subchronic studies, the lowest NOEL is 50 ppm based on a rat study. Subchronic Dermal Toxicity: For female rats r eceiving dermal applications of cyprodinil; NOEL was 5 mg/kg/.day; the NOEL for the male rats in this study is 125 mg/kg/day. 5. Chronic toxicity. Chronic Oral Toxicity: Two chronic studies found NOELs of 75 ppm in a 24 - month rat study and 2500 ppm in a one -year Beagle study. Neither study found evidence of carcinogenicity for cyprodinil. 6. Animal metabolism. The metabolism of cyprodinil in rats is adequately understood. 7. Metabolite toxicology

. Th e residue of concern for tolerance setting purposes is the parent compound. The EPA has reviewed the hazard profile of the pryimidine metabolites (CGA - 249287, NOA - 422054) of cyprodinil. EPA has concluded that the toxicity of the CGA - 249287 and NOA - 422054 m etabolites is no greater than that of the parent. 8. Endocrine disruption

. Cyprodinil does not belong to a class of chemicals known or suspected of having adverse effects on the endocrine system. Developmental toxicity4

studies in rats and rabbits and a reproduction study in rats gave no indication that cyprodinil might have any effects on endocrine function related to development and reproduction. The chronic studies also showed no evidence of a long - term effect related to the endocrine system. C. Aggregate Exposure 1. Dietary exposure. Tier III acute and chronic dietary exposure evaluations were performed for cyprodinil using the Dietary Exposure Evaluation Model (DEEM FCID TM , version 2.16) from Exponent. These cyprodinil exposure assessments included all current and pending uses and proposed uses on tree nuts (14 - day PHI). These assessments utilized residue data from field trials where cyprodinil was applied at the maximum intended use rate and samples were ha rvested at the minimum pre - harvest interval (PHI) to obtain maximum residues. Empirically derived processing factors for apple juice (0.39X), apple pomace (5.22X), grape juice (0.29X), dried prune (2.05X), tomato puree (0.52X), and tomato paste (2.3X) wer e used in these assessments. All other processing factors used the DEEM - FCID TM Version 7.87 defaults. All consumption data for these assessments was taken from the USDA’s Continuing Survey of Food Intake by individuals (CSFII) with the 1994 - 96 consumptio n database and the Supplemental CSFII children’s survey (1998) consumption database. The percent of crop treated value was assumed to be 100% for all commodities. Secondary residues in beef liver and kidney were estimated based on “maximum reasonably bal anced diets” and transfer information from feeding studies. i. Food. Acute exposure

. The acute dietary (food only) risk assessment for females 13 - 49 years old (the only population subgroup for which an acute toxicological endpoint has been established ) was performed using an acute reference dose (aRfD) of 1.5 mg/kg - bw/day, based upon a rabbit study with a no observed adverse effect level (NOAEL) of 150 mg/kg - bw/day and an uncertainty factor (UF) of 100X for intra - and inter - species variations; no additional FQPA safety factor was applied. For the purpose of the aggregate risk assessment, the exposure value was expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup. In add ition, exposure was expressed as a percent of the acute reference dose (%aRfD). Acute food exposure to the females 13 - 49 years subpopulation resulted in a MOE of 3,517 (2.8% of the aRfD of 1.5 mg/kg - bw/day). Since the Benchmark MOE for this assessment wa s 100 and since the EPA generally has no concern for exposures below 100% of the reference dose, Syngenta believes that there is a reasonable certainty that no harm will result from acute dietary (food) exposure to residues arising from all current, pendin g, and proposed uses for cyprodinil. Chronic exposure. The chronic reference dose (RfD) for cyprodinil is 0.03 mg/kg - bw/day, based on a chronic rat study with a NOAEL of 2.7 mg/kg bw/day and an uncertainly factor of 100X for intra - and inter - species variations; no additional FQPA safety fact or was applied. For the purpose of the aggregate risk assessment, the exposure values were expressed in terms of margin of exposure5

(MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup. In addition, exposure was expressed as a percent of the chronic reference dose (%cRfD). Chronic food exposures to the U.S. population resulted in a MOE of 1,015 (8.9% of the cRfD of 0.03 mg/kg - bw/day). Chronic food exposures to the most sensitive subpopulation (children 1 - 2 yea rs old) resulted in a MOE of 347 (25.9% of the cRfD of 0.03 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures below 100% of the reference dose, Syngenta believes that there is a rea sonable certainty that no harm will result from chronic dietary (food) exposure to residues arising from all current, pending, and proposed uses for cyprodinil. ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of cyprodinil and it s degradate CGA249287, reported as combined total residues (cyprodinil plus CGA249287), were determined for the proposed use on tree nuts using Tier l SCI - GROW (version 2.3), which estimates pesticide concentrations in ground water and Tier II PRZM/EXAMS ( PE version 5.0) which estimates pesticide concentrations in surface water. For ground water, the currently registered uses on almond and grapes and proposed use on tree nuts provided the highest combined EDWC of 0.1076 ppb (acute and chronic). For surfa ce water, the grape (aerial) use provided the highest combined EDWCs of 39.417 ppb for acute and 22.691ppb for chronic. The surface water EDWCs have been corrected for a 0.87 PCA factor. Since the surface water EDWCs exceed the ground water EDWC, the su rface water values will be used for risk assessment purposes and considered protective for any ground water exposure concerns. Acute Exposure from Drinking W ater : The acute EDWC of 39.417 ppb (0.039417 ppm) was incorporated with food residues as “water, direct and indirect, all sources” directly into the DEEM - FCIDTM software to model the aggregate (food and water) exposures. The acute drinking water exposure contributions at the 99.9 th percentile of exposures were determined by taking the difference betwe en the aggregate (food + drinking water) exposures and the food (only) exposures for each population subgroup. Acute drinking water exposure at the 99.9 th percentile for females (13 - 49 years), the only population subgroup for which an acute toxicological endpoint has been established, resulted in a MOE of 211,566 (<0.1% of the aRfD of 1.5 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100, and since the EPA generally has no concern for exposures below 100% of the reference dose, Syngenta b elieves that there is a reasonable certainty that no harm will result from acute drinking water exposure to residues arising from all current, pending, and proposed uses for cyprodinil. Chronic Exposure from Drinking W ater : The chronic EDWC of 22.691 ppb (0.022691 ppm) was incorporated with food residues as “water, direct a nd indirect, all sources” directly into the DEEM - FCIDTM software to obtain chronic dietary (drinking water) exposures. Chronic drinking water exposure to the U.S. population resulted in a MOE of 5,645 (1.6% of the RfD of 0.03 mg/kg - bw/day). The most sensitive subpopulation was all infants (<1 year old), with a MOE of 1,7226

(5.2% of the RfD of 0.03 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures below 100% of the reference dose, Sy ngenta believes that there is a reasonable certainty that no harm will result from chronic drinking water exposure to residues arising from all current, pending, and proposed uses for cyprodinil. 2. Non

- dietary exposure

. Cyprodinil is not currently reg istered for any uses that would result in residential handler (mixer/loader/applicator) exposure. A new product label for Palladium®, containing cyprodinil and fludioxonil, allows professional applications to ornamental plants in residential settings. No postapplication residential exposure assessment is required because post - application exposure to adults and children from ornamental applications is negligible. D. Cumulative Effects Cumulative Exposure to Substances With a Common Mechanism of Toxicity . Section 408(b)(2)(D)(v) 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 tha t have a common mechanism of toxicity”. The EPA does not have, at this time, available data to determine whether cyprodinil has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. For the purposes of this tolerance action, the EPA has not assumed that cyprodinil has a common mechanism of toxicity with other substances. E. Safety Determination 1. U.S. population. An acute toxicological endpoint has not been established for the U.S. po pulation, so an acute exposure assessment was not performed for the U.S. population. The chronic aggregate exposure analysis showed that exposure from all current and proposed cyprodinil uses resulted in a MOE of 860 ( 10 . 5 % of the c RfD of 0.03 mg/kg - bw/day) for the U.S. population, which exceeds the Benchmark MOE of 100. A cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for cyprodinil. Based on the completeness and reliability of the toxicity data su pporting these petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure from all current and proposed uses of cyprodinil. 2. Infants and children

. A n acute toxicological endpoint has not been est ablished for infants and children, so an acute exposure assessment was not performed for infants and children. The chronic aggregate exposure analysis showed that exposure from all established and proposed cyprodinil uses resulted in a MOE of 318 ( 28 . 3 % o f the c RfD of 0.03 mg/kg - bw/day) for children 1 - 2 years old, which exceeds the Benchmark MOE of 100. A cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for cyprodinil. Based on the completeness and re liability of the toxicity data supporting these petitions, Syngenta7

believes that there is a reasonable certainty that no harm will result from aggregate exposure from all current and proposed uses of cyprodinil. 3. Females 13

- 49 years of age

. The acute aggregate exposure analysis showed that exposure to all current and proposed cyprodinil uses would result in a MOE of 3,459 ( 2 . 9 % of the aRfD of 1.5 mg/kg - bw/day) for females 13 - 49 years old, which exceeds the Benchmark MOE of 100. The chronic aggregate e xposure analysis showed that exposure to all current and proposed cyprodinil uses would result in a MOE of 1,039 ( 8.7 % of the c RfD of 0.03 mg/kg - bw/day) for females 13 - 49 years old, which exceeds the Benchmark MOE of 100. A cancer exposure analysis was no t performed, since there is no evidence of human carcinogenic potential for cyprodinil. Based on the completeness an d reliability of the toxicity data supporting these petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure from all current and proposed uses of cyprodinil. F. International Tolerances Codex maximum residue levels have been established for residues of cyprodinil in or on almonds, apples, barley, beans (except broad bean and soya bean), cucumbers, dried grapes (currants, raisins and sultanas), eggplant, eggs, grapes, lettuce (head & leaf), mea t & meat- by - products, milk, onions (bulb), pears, peppers (sweet), poultry, prunes, raspberries, squash (summer), stone fruits, straw and fodder of cereal grains, strawberries, tomatoes, wheat, and wheat bran.