**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR**

**PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER (**  **5 /** **7 /20**  **1 4**  **) EPA Registration Division contact:**  **Shaja Joyner , (703)**  **308 -** **3194**

**TEMP LATE:**  **Syngenta Crop Protection, LLC P#4F8277**  EPA has received a pesticide petition **( 4F**  **8277 )**  from **Syngenta Crop Protection, LLC**  **, 410 Swing Road**  **, Greensboro**  **, N C**  **27409** proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFD CA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 .516

. 1. by establishing the tolerance for residues of **flud io**  **xonil: [4 -**  **(2, 2 -**  **difluoro -**  **1,3 -**  **benzodioxol -**  **4 -** **yl) -**  **1H -**  **pyrrole -** **3 -**  **carbonitrile]** in or on the raw agricultural commodity **Rapeseed S**  **ubgroup 20A , excep**  **t flax seed**  at **0.01 parts per million.** Upon approval of the aforementioned tolerances, it is proposed that 40 CFR 180.5 16 be amended to remove the established tolerances for the residues of fludioxonil in or on the raw agricultural commodity : **Rapeseed, seed**  **, at 0.01**  **parts 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 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 metabolism**. The metabolism of fludioxonil is adequately understood for**  **the purpose of the proposed toleran ces.**  2. Analytical method. **Syngenta has developed and validated analytical methodology for enforcement purposes. This method (Syngenta Crop Protection Method AG** **** **597B) has passed an Agency petition method validation for several commodities,**2

**and is curren tly the enforcement method for fludioxonil. This method has also been**  **forwarded to the Food and Drug Administration for inclusion into PAM II. 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 adequately supported by**  **previously submitted studies MRIDs 44703528 , 44703528**  **and 44703530. In support of the requested t**  **olerance s**  **, Syngenta**  **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 fludioxonil**  **in or on requested commodities.**  B. Toxicological Profile EPA has evaluated the available toxicity data 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 variabi lity 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

- effect

- level (NOAEL) from the toxicity studies can be found at the following website: http://edocket.access.gpo.gov/2012/2012

- 19988.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 15, 2012 (77 FR pages 48907

- 48915) (FRL

- 9357

- 5). **1. Acute toxicity.**  **[Insert text.] 2.**  **Genotoxicty. [Insert text.]**  **3. Reproductive and developmental toxicity.**  **[Insert text.] 4.**  **Subchronic 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 III acute and chronic die tary exposure evaluations were** 3

**performed for fludioxonil using the using the Dietary Exposure Evaluation Model (DEEM**  **- FCIDTM Version 3.16) from Exponent; consumption data was from the**  **USDA NHANES “What We Eat in America” survey, 2003 -**  **2008. These exposure as**  **sessments included all current and proposed**  **uses as well as a proposed crop**  **group extension of Rape**  **seed C**  **rop G**  **roup 20A , except flax, seed**  **. These assessments**  **utilized residue data from field trials where fludioxonil was applied at the maximum intended use**  **rate. Secondary residues in animal commodities were estimated based on “maximum reasonably balanced diets” and transfer information from**  **metabolism studies.** i. Food. Acute exposure

. **The acute dietary (food only) risk assessment for females 13 to 49 yea**  **rs old (the only population subgroup for which an acute toxicological endpoint has been established) was**  **performed using an acute reference dose (aRfD) of 1.0 mg/kg**  **- bw/day, based upon a rat teratology study with**  **a no observed adverse effect level (NOAEL) o**  **f 100 mg/kg/day and an uncertainty factor (UF) of 100X for intra**  **- and inter** **- species variations**  **. N**  **o additional FQPA safety factor was applied. For the purpose of the aggregate risk assessment, the exposure value was expressed**  **in terms of margin of exposur e (MOE), which was calculated by dividing the no**  **observed adverse effect level (NOAEL) by the exposure for each population subgroup. In addition, exposure was expressed as a percent of the acute reference**  **dose (% aRfD). At the 99.9th percentile, acute (f**  **ood only) exposure to the females 13**  **- 49 years subpopulation resulted in a MOE of 1,683 (5.9% of the aRfD of 1**  **.0 mg/kg**  **- bw/day). Since the Benchmark MOE for this assessment was 100 and since**  **the EPA generally has no concern for exposures above the Benchmark MOE or**  **below 100% of the aRfD , Syngenta believes that there is a reasonable certainty that**  **no harm will result from dietary (food only** **) exposure to residues arising from the current, pending and proposed uses for fludioxonil.**  Chronic exposure. **The chron ic dietary (food only) risk assessment was performed**  **for all population subgroups using a chronic reference dose (cRfD) of 0.033 mg/kg**   ** bw/day, based upon a one** **- year study in dogs with a NOAEL of 3.3 mg/kg**  **- bw/day**  **and an uncertainly factor of 100X to account for intra**  **- and inter** **- species variations.**  **No additional FQPA safety factor was applied. For the purpose of the chronic aggregate risk assessment, the exposure values were expressed in terms of margin of**  **exposure (MOE), which was calculated by dividing th e no observed adverse effect**  **level (NOAEL) by the exposure for each population subgroup. In addition, exposure was expressed as a percent of the chronic reference dose (% cRfD).**  **Chronic (food only) exposure to the U.S. population resulted in a MOE of 747 (13.4% of the cRfD of 0.033 mg/kg**  **- bw/day). The most exposed sub**  **- population was**  **children (1 -**  **2 years old) with a MOE of 227 (44.0% of the cRfD of 0.033 mg/kg**  **** **bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no c**  **oncern for exposures above the Benchmark MOE or below 100% of the cRfD, Syngenta believes that there is a reasonable certainty that no harm will**  **result from dietary (food only) exposure to residues arising from the current, pending and proposed uses for fl** **udioxonil.**4

ii. Drinking water. **The Estimated Drinking Water Concentrations (EDWCs) of fludioxonil were determined using Tier l SCI**  **- GROW and PRZM**  **- GW, which**  **estimates pesticide concentrations in ground water and Tier II PRZM/EXAMS which estimates pesticide**  **concentrations in surface water. This drinking water assessment was conducted to assess all currently registered uses and**  **the proposed**  **post -**  **harvest use on carrots. For ground water, the PRZM**  **- GW model provided the**  **highest EDWCs of 25.7 ppb and 24.6 ppb fo r acute and chronic, respectively, based**  **on the currently registered use on turf. For surface water, the currently registered field grown and landscape ornamental provided the highest acute EDWC of 44.1**  **ppb (no Percent Cropped Area (PCA) adjustment) and t he currently registered use**  **on turf provided the highest chronic EDWC of 34.8 ppb (adjusted for 0.95 PCA). Since the surface water EDWCs exceed the ground water EDWC, the surface water**  **values were used for risk assessment purposes and will be considered p rotective for**  **any ground water exposure concerns.** Acute Exposure from Drinking W ater : **The acute EDWC of 44.1 ppb was incorporated with food residues as “water, direct and indirect, all sources” directly into the**  **DEEM -**  **FCIDTM software to obtain acute dietar y (water) exposures. Drinking water**  **exposures at the 99.9th percentile to fludioxonil for females 13 -**  **49 years old (the only population subgroup for which an acute toxicological endpoint has been established)**  **resulted in a MOE of 94,073 (0.1% of the aRfD o f 1.0 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 aRfD, Syngenta 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 fludioxonil uses.** Chronic Exposure from Drinking W ater : **The chronic EDWC of 34.8 ppb was incorporated with food residues as “water, direct and indirect, all sources” directly**  **into the DEEM -**  **FCIDTM software to obtain chronic dietary (water) exposures. Chronic drinking water exposure to the U.S. population resulted in a MOE of 4,529**  **(2.2% of the cRfD of 0.033 mg/kg -**  **bw/day). The most sensitive sub -**  **population was all infants (<1 year old), with**  **a MOE of 1,756 (5.7% of the cRfD of 0.033 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 cRfD, Syngenta believes that there is a reasonable certainty that no ha**  **rm will result from chronic drinking water exposure to residues arising from all current and proposed fludioxonil uses** 

**.** Cancer

. **A chronic cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for fludioxon**  **il.** 2. Non

- dietary exposure

. . **Residential exposure risk assessments were performed for use of fludioxonil formulated as Palladium** **TM for ornamentals and Medallion**  **® for**  **turf and ornamentals and and Medallion ®**  **TL for turf. Palladium** **TM may not be used**  **on residential ornamental plants; therefore, no residential handler exposure**  **assessments are required for this product. Medallion ®**  **and Medallion ®**  **TL are intended primarily for professional use however, the product label does not exclude** 5

**residential uses; th erefore, a residential handler exposure assessment was**  **conducted. The following endpoints were used: a 10 mg/kg/day NOAEL for adults (inhalation only) from a rabbit developmental tox study; a 10 mg/kg/day short**  **- term**  **NOAEL for children 1 -**  **6 years (incidenta l oral) from an oral rabbit developmental**  **study; a 3.3 mg/kg/day intermediate -**  **term NOAEL for children 1 -**  **6 years (incidental oral) from a one**  **- year feeding study in dogs. Residential handler exposure risk from**  **fludioxonil was acceptable (MOE = 69,140; shor t** **- term) for youths (13**  **- 19 years)**  **and adults (19+ years) treating residential turf with a hose -**  **end sprayer. Residential handler exposure scenarios are considered to be short** **- term only, due to the**  **infrequent use patterns associated with homeowner products. Since no dermal**  **endpoints were selected short -**  **and intermediate -**  **term assessments were not conducted for post** **- application exposure risk to children, youth or adults. Post**  **** **application non -**  **dietary oral hand -**  **to -**  **mouth exposure risks for children 1 -**  **6 years, re**  **sulting from contact with treated lawns were acceptable for short -**  **term (MOE = 911) and intermediate**  **- term (MOE = 301) durations. Since the MOEs for children**  **(1 -**  **6 years), youths (13 -**  **19 years) and adults (19+ years) were above the Benchmark MOE of 100, resid**  **ential exposure risk for fludioxonil do not exceed the EPA’s Level of Concern.**  D. Cumulative Effects Cumulative Exposure to Substances with a Common Mechanism of Toxicity

. **Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to estab**  **lish, 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.” Unlike other pesticides for**  **which the EPA has followed a cumulative risk approach based on a common**  **mechanism of toxicity, the EPA has not made a common mechanism of toxicity finding as to fludioxonil and any other substances, and fludioxonil does not appear**  **to produce a toxic metabolite produ ced by other substances. For the purposes of**  **this tolerance action, the EPA has not assumed that fludioxonil has a common mechanism of toxicity with other substances.**  E. Safety Determination 1. U.S. population. **An acute toxicological endpoint has not be en established for the**  **U.S. population, 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 fludioxonil uses resulted in a MOE of 641 or 15.6 % of the**  **cRfD (Benchmark MOE = 100; cRfD=0.033 mg/kg -**  **bw/day). A cancer exposure analysis was not performed since there is no evidence of human carcinogenic**  **potential for fludioxonil. Since the worst -**  **case aggregate MOE of 641 exceeds the benchmark MOE of**  **100, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current,**  **pending and proposed fludioxonil uses, including anticipated dietary exposure from food, water, and all other**  **types of non -**  **occupational exposures.**6

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 a nalysis showed that exposure from**  **all established and proposed fludioxonil uses resulted in a MOE of 212 or 47.2% of the cRfD (Benchmark MOE = 100; cRfD=0.033 mg/kg**  **- bw/day) for children (1**  **- 2**  **years old). A cancer exposure analysis was not performed, since there is no evidence**  **of human carcinogenic potential for fludioxonil. The short -**  **term aggregate assessment resulted in MOE of 422, for the children (1**  **- 6 years old) population**  **subgroup (Benchmark MOE = 100). The intermediate -**  **term aggregate assessment res**  **ulted in MOE of 139, for the children (1 -**  **6 years old) population subgroup (Benchmark MOE**  **= 100). A cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for fludioxonil. Since the**  **worst -**  **case aggregate MOE of 139 exceeds the Benchmark MOE of 100, Syngenta**  **believes that there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current, pending and proposed fludioxonil**  **uses, including anticipated dietary expo sure from food, water, and all other types of**  **non -**  **occupational exposures.** 3. Females 13

- 49 years of age

. **The acute aggregate exposure analysis showed that exposure to all current, pending and proposed fludioxonil uses would result in a**  **MOE of 1,654 or 6. 1% of the aRfD (Benchmark MOE = 100; aRfD=**  **1.0 mg/kg**  **** **bw/day) for females 13 -**  **49 years old. The chronic aggregate exposure analysis showed that exposure to all current and proposed fludioxonil uses would result in a**  **MOE of 773 or 12.9% of the cRfD (Benchmar k MOE = 100; cRfD= 0.033 mg/kg**  **** **bw/day) for females 13 -**  **49 years old. A cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for fludioxonil. Since the**  **worst -**  **case aggregate MOE of 773 exceeds the Benchmark M OE of 100, Syngenta**  **believes that there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current, pending and proposed fludioxonil**  **uses, including anticipated dietary exposure from food, water, and all other types of**  **non -**  **occupational exposures.** F. International Tolerances **Codex Maximum Residue Limits (MRLs) for residues of fludioxonil per se**  **have been established on a number of commodities, apple pomace, dry, basil, basil, dry,**  **beans (dry), beans, she lled, blackberries, blueberries, broccoli, cabbages, head,**  **carrot, cereal grains, chives, chives, dry, citrus fruits, cotton seed, cucumber, dewberries (including boysenberry and loganberry), edible offal (mammalian),**  **eggplant, eggs, grapes, kiwifruit, let tuce, head, meat (from mammals other than**  **ma rine mammals), melons, except watermelon, milks, mustard greens, onion, bulb,**  **peas (dry), peas (pods and succulent=immature seeds), peas, shelled (succulent seeds), peppers, sweet (including pimento or pimiento),**  **pistachio nuts, pome fruits, pomegranate, potato, poultry meat, poultry, edible offal of, rape seed, raspberries,**  **red, black, soya bean (dry), squash, summer, stone fruits, straw and fodder (dry) of cereal grains, strawberry, sunflower seed, sweet corn (c**  **orn -**  **on -**  **the -**  **cob), sweet**7

**potato, tomato, watercress, and yams.**