EPA REGI STRATION DIVISION COMPANY NOTICE OF FILING FOR PESTI CI DE

PETI TI ONS PUBLISHED IN THE FEDERAL REGI STER ( 11 /25 /20 1 3 ) Interregional Research Project Number 4 (IR - 4) Petition Number, PP#, 4E8273 EPA has received a pesticide petitio n, PP# 4E8273, f rom Interregional Research Project Number 4, IR - 4 , 500 College Road East, Suite 201 W, Princeton, NJ 08540 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 by establ ishing the tolerance for residues of cy prodinil, 2 - Py

rimidinamine, 4 - cycloprop yl - 6 - methyl - N phenyl - ] , in or on the raw agricultural commodit ies artichoke , globe at 4 .0 parts per million (ppm); a cerola at 1.5 ppm; f eijoa at 1.5 ppm; guava at 1.5 ppm; j aboti caba at 1.5 ppm; p assionfruit at 1.5 ppm ; s tarfruit at 1.5 ppm ; w ax jambu at 1.5 ppm ; f ruit , stone group 1 2 - 1 2 at 2.0 pp m ; and p omegranate at 7.0 ppm . Upon approval of the aforementioned tolerances, it is proposed that 40 CFR 180.532 be amended to remove the established tolerance for the residues of cy prodinil in or on the raw agricultural commodity f

ruit, stone , group 12 at 2.0 ppm. 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 data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metaboli

sm. The metabolism of cy prodinil is adequately

understood for the purpose of the proposed tolerances. The metabolism of cy prodinil has been characterized in plants and animals. No toxicologically significant metabolites have been identified. The metaboli sm profile supports the use of an analy tical enforcement method that accounts for only

parent cy prodinil. 2. Analytical method. Syngenta Crop Protection has developed and validated anal yt ical methodology

for enforcement purposes. This method (Sy ngenta Cro p Protection Method AG - 631B) has passed an Agency petition method validation for several commodities and is currentl y the enforcement method for cyprodinil. An extensive database of method validation data using this method on various crop commodities is av ailable. 3. Magnitude of residues. Complete residue data to support the reque sted tolerances have been submitted. The requested tolerances are adequately supported. In support of the requested tolerance, IR - 4 has conducted the necessary trials in accordance with the requirements of the EPA Residue Chemistry Guidelines 860.1500 to determine the magnitude of residue of cy prodinil in or on requested commodities .2

B. Tox icological Profile EPA has evaluated the available toxicity d ata and considered its validity , completeness, and reliability

a s well as the relationship of the results of the studies to human risk. E PA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. S pecific information on the studies received and the nature of the toxic effects caused by fludioxonil as well as the no - observed - adverse - ef fect - level (NOAEL) from the toxicity studies can be found at the following website: http://edocket.access.gpo.gov/2012/2012 - 20235 .htm. A

s ummary of the toxicological endpoints for fludioxonil used for human risk assessment is discussed in Unit III.A and B . of the final rule published in the Federal Register of August 1 7 , 2012 (77 FR pages 49732 - 4 9738 ) (FRL - 935 9 - 7 ). 1. Acute toxicity. [Insert text.] 2. Genotoxicty. [Insert text.] 3. Reproductive and developmental toxicity. [Insert text.] 4. Subchron ic toxicity. [Insert text.] 5. Chronic toxicity. [Insert text.] 6. Animal metabolism. [Insert text.] 7. Metabolite toxicology . [Insert text.] 8. Endocrine disruption . [Insert text.] C. Aggregate Exposure 1. Dietary exposure. Tier II acute and chronic dietary exposure evaluations were performed for cy

prodinil using the Dietary Exposure Evaluation Model (DEEM - FCIDTM Version 3.16) from Exponent and consumption data from the USDA NHANES “What We Eat in America” survey , 2003 - 2008. These cyprodinil exp osure assessments included all current and pending uses plus proposed new IR - 4 uses on artichoke, guava, cucumbers (greenhouse), tomatoes (greenhouse and cherry), a postharvest use on pomegranate, and an extension of existing stone fruit tolerances to all of Crop Group 12 - 12. These assessments utilized residue data from field trials where cy prodinil was applied at the maximum intended use rate and samples were harvested at the minimum pre - harvest interval (PHI) to obtain maximum residues. Empirically deri ved 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) were used in these assessments; all other processing factors used the DEEM - FCID TM Version 7.87 def aults. The percent3

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 balanced diets” and transfer information from feeding studies. i. Food. Acute e

xposure . The acute dietary (food only) risk assessment for females 13 - 49 years old (the onl y 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 uncertaint y factor (UF) of 100X for intra - and inter - species variations; no additional FQPA safety factor was applied. For the purpose of the aggregate risk ass essment, the exposure value was expressed in terms of margin of exposure (MOE), which was calculated b y dividing the NOAEL b y the exposure for each population subgroup. In addition, exposure was expressed as a percent of the acute reference dose (%aRfD). Acute food exposure to the females 13 - 49 y ears subpopulation resulted in a MOE of 2,085 (4.8% of the aRfD of 1.5 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generall y has no concern for exposures below 100% of the reference dose, Sy ngenta believes that there is a reasonable certaint y that no harm will result from acute dietary (food) exposure to residues arising from all current, pending, and proposed uses for cy prodinil. Chronic exposure. The chronic reference dose (RfD) for cy prodinil is 0.027 mg/kg - bw/day , based on a chronic rat study with a NOAEL of 2.7 mg/kg - bw/day and an uncertainl y factor 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 v alues were expressed in terms of margin of exposure (MOE), which was calculated b y dividing the NOAEL b y the exposure for each population subgroup. In addition, exposure was expressed as a percent of the chronic reference dose (%cRfD). Chronic food expos ures to the U.S. population resulted in a MOE of 473 (21.1% of the cRfD of 0.027 mg/kg - bw/day). Chronic food exposures to the most sensitive subpopulation (children 1 - 2 y ears old) resulted in a MOE of 196 (51.1% 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, Sy ngenta believes that there is a reasonable certainty that no harm will result from chronic dietary

(food) exposure t o residues arising from all current, pending, and proposed uses for cy

prodinil. ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of cy prodinil and its degradate CGA249287, reported as combined total residues (cy prodinil plus CGA2492 87), were determined for the currently registered uses as well as proposed uses on artichoke, guava, green - house cucumbers, green - house tomatoes, and post harvest pomegranate 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 currentl y registered uses on almond and grapes provided a combined EDWC of 0.0861 ppb (acute and chronic). For surface water, the registered use on peppers provided a combined4

acute EDWC of 46.9 ppb and the currentl y registered use on grapes provided a combined chronic EDWC of 27.1 ppb. No Percent Cropped Area adjustments were made to the surface water EDWCs. Since the s urface water EDWCs exceed the ground water EDWC, the surface water values were used for risk assessment purposes and considered protective for an y ground water exposure concerns. Acute Exposure from Drinking W ater : The acute EDWC of 46.9 ppb was incorpor ated 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 determ ined by taking the difference between 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 y ears), the only population subgroup for which an acute toxicological endpoint has been established, resulted in a MOE of 201,072 (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 generall y has no concern for exposures below 100% of the aRfD, Sy ngenta believes that there is a reasonable certainty that no harm will result from acute drinking water exposure to residues arising from all current and proposed uses of cy prodinil. Chronic Exposure from Drinking W ater : The chronic EDWC of 27.1 ppb was incorporated with food residues as “water, direct and indirect, all sources” directly into the DEEM - FCIDTM software to obtain chronic dietary (food and water) exposures. Chronic drinking water exposure to the U.S. population resulted in a M OE of 4,758 (2.1% of the cRfD of 0.027 mg/kg - bw/day). The most sensitive subpopulation was all infants (<1 ye ar old), with a MOE of 1,845 (5.4% of the cRfD of 0.027 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA gene rall y has no concern for exposures below 100% of the RfD, 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 and proposed uses of cy prodinil. 2. Non
- die tary exposure . Cy prodinil is not currently

registered for an y uses that would result in residential handler (mixer/loader/applicator) exposure. The product label for Palladium®, containing cyprodinil and fludioxonil, allows professional applications to o rnamental plants in residential settings. No post - application 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 pest icide’s residues and “other substances that have a common mechanism of toxicity”. The EPA does not have, at this time, available data to determine whether5

cy prodinil 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 cy prodinil has a common mechanism of toxicity with other substances. E. Safety Determination 1. U.S. population. An acute toxicological endpoint ha s not been established for the U.S. population, so an acute exposure assessment was not performed for the U.S. population. The chronic aggregate exposure anal ys is showed that exposure from all current and proposed cy

prodinil uses resulted in a MOE of 430 (23.2% of the cRfD of 0.027 mg/kg bw/day) for the U.S. population, which exceeds the Benchmark MOE of 100. A cancer exposure anal ys is was not performed, since there is no evidence of human carcinogenic potential for cy

prodinil. Based on the completeness and reliability of the toxicity

data supporting these petitions, Sy ngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure from all current, pending, and proposed uses of cy prodinil. 2. Infants and children . An acute toxicological endpoint has not been established for infants and children, so an acute exposure assessment was not performed for infants and children. The chronic aggregate exposure anal ys is showed that exposure from all established and proposed c yp rodinil uses resulted in a MOE of 185 (54.1% of the cRfD of 0.027 mg/kg - bw/day) for children 1 - 2 y ears old, which exceeds the Benchmark MOE of 100. A cancer exposure anal ys is was not performed, since there is no evidence of human carcinogenic potential for cy prodinil. Based on the completeness and reliability of the toxicity

data supporting these petitions, Sy ngenta believes that there is a reasonable certaint y that no harm will result from aggregate exposure from all current, pending, and proposed uses of cy

prodinil. 3. Females 13
- 49 years of age . The acute aggregate exposure anal ys is showed that exposure to all current and proposed cy prodinil uses would result in a MOE of 2,064 (4.8% of the aRfD of 1.5 mg/kg - bw/day) for females 13 - 49 y ears old, which exceeds the Benchmark MOE of 100. The chronic aggregate exposure analy sis showed that exposure to all current and proposed cy prodinil uses would result in a MOE of 483 (20.7% of the cRfD of 0.027 mg/kg - bw/day) for females 13 - 49 years old, which exceeds the Benchmark MOE of 100. A cancer exposure analy sis was not performed, since there is no evidence of human carcinogenic potential for cy prodinil. Based on the completeness and reliability

of the toxicity

data supporting these petitions, Sy ngenta believes that there is a reasonable certaint y that no harm will result from aggregate exposure from all current, pending, and proposed uses of cy prodinil. F. International Tolerances In 2005 the Codex Alimentarius Commission established M aximum R esidue Li mits (M RL s) for cy

prodinil in or on various agricultural commodities including almond hulls,6

almonds, apple, barley , beans (except broad bean and soy bean), cucumber, dried grapes (currants, raisins, and sultanas), edible offal, eggplant, grapes, lettuce (head an d leaf), bulb onion, pear, sweet peppers, prunes, raspberries (red and black), summer squash, stone fruits, straw and fodder of cereal grains, strawberry , tomato, wheat, and various meat, milk, and egg commodities.