


EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: Cynthia Giles-Parker, 703-305-7740


TEMPLATE:

Syngenta Crop Protection, LLC

9E8798

	EPA has received a pesticide petition (9E8798) from Syngenta Crop Protection, LLC, P.O. Box 18300, Greensboro, NC 27419-8300 requesting, 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

   
   	by establishing an import tolerance for residues of
	
	Fludioxonil (4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1-H-pyrrole-3-carbonitrile) in or on the raw agricultural commodity banana at 2.0 parts per million (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 fully 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 tolerances.  

	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, and is currently 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 import tolerance has been submitted and the requested import tolerance is adequately supported. 


B. Toxicological Profile

EPA has evaluated the available toxicity data and considered its 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.  Specific 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://regulations.gov page 17 of the document titled "Fludioxonil  -  Preliminary Human Health Risk Assessment for Registration Review,'' in Docket ID Number EPA - HQ - OPP - 2010-1067.  A summary of the toxicological endpoints for fludioxonil used for human risk assessment is discussed in Section III, Subsection A of the final interim decision for registration review published in the Federal Register on December 04, 2018 (Docket ID Number EPA-HQ-OPP-2010-1067-0037). 
	1. Acute toxicity.  See above.

	2. Genotoxicty. See above.

	3. Reproductive and developmental toxicity. See above.

	4. Subchronic toxicity. See above.

	5. Chronic toxicity. See above.

	6. Animal metabolism. See above.

	7. Metabolite toxicology. See above.

	8. Endocrine disruption. See above.

C. Aggregate Exposure

	1. Dietary exposure. Tier III short-term and chronic dietary exposure evaluations were performed for fludioxonil using the using the Dietary Exposure Evaluation Model (DEEM-FCID(TM) Version 4.02) from Exponent; consumption data was from the USDA NHANES "What We Eat in America" survey, 2005-2010.  These assessments included all current and pending uses as well as a proposed import tolerance on bananas.  These assessments utilized residue data from field trials where fludioxonil was applied at the maximum intended use rate and samples were harvested at the minimum pre-harvest interval (PHI) to obtain the maximum expected residues. Updated 2019 estimated percent crop treated (%CT) values were incorporated into the Tier III assessments based upon economic, pest, and competitive pressures.  Secondary residues in animal commodities were estimated based on "maximum reasonably balanced diets" and transfer information from feeding and metabolism studies.  Drinking water estimates were incorporated directly into the chronic dietary exposure assessment using the highest estimated drinking water concentrations (EDWCs) for surface and ground water.

 Food. Acute exposure. Acute dietary (food only) assessments were not performed, since an endpoint of concern attributable to a single oral dose has not been identified.  
            
            Chronic exposure.  The chronic dietary (food only) risk assessment was performed for all population subgroups using a chronic reference dose (cRfD) of 0.33 mg/kg-bw/day, based upon a one-year study in dogs with a NOAEL of 33.1 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 the 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 6,096 (1.6% of the cRfD of 0.33 mg/kg-bw/day).  The most exposed sub-population was children (1 2 years old) with a MOE of 1,740 (5.8% of the cRfD of 0.33 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 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 fludioxonil.

            Cancer.  A chronic cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for fludioxonil.

 Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of fludioxonil were determined using the Pesticide in Water Calculator (PWC v1.52).  PWC is a graphical user interface that incorporates the Pesticide Root Zone Model/Variable Volume Water Model (PRZM/VVWM) Tier II surface water and Tier I PRZM ground water (PRZM-GW) models.  This drinking water assessment was conducted to assess all currently registered and pending uses.  The highest chronic surface water EDWC was 17.7 ppb, based on the existing use on ornamentals with no Percent Cropped Area (PCA) adjustment. The highest chronic ground water EDWC was 48.34 ppb, based on the existing use on turf. Since the ground water EDWC exceeds the surface water EDWC, the ground water value was used for risk assessment purposes and will be considered protective for any surface water exposure concerns.  
            
            Acute Exposure from Drinking Water:  Acute drinking water assessments were not performed, since an endpoint of concern attributable to a single oral dose has not been identified.

            Chronic Exposure from Drinking Water:  The chronic EDWC of 48.34 ppb was incorporated with food residues as "water, direct and indirect, all sources" directly into the DEEM-FCID(TM) software to obtain chronic dietary (water) exposures.  Chronic drinking water exposure to the U.S. population resulted in a MOE of 33,890 (0.3% of the cRfD of 0.33 mg/kg-bw/day).  The most sensitive sub-population was all infants (<1 year old), with a MOE of 9,073 (1.1% of the cRfD of 0.33 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 harm will result from chronic drinking water exposure to residues arising from all current and proposed fludioxonil uses.

	2. Non-dietary exposure. Residential exposure risk assessments were performed for use of fludioxonil formulated as Instrata, Medallion, Medallion II, Medallion SC, Medallion WDG, and Palladium for ornamentals and residential turf.  Medallion(R) and Medallion(R) SC are intended primarily for professional use however, the product label does not exclude residential uses; therefore, a residential handler exposure assessment was conducted.  Residential exposure assessments were performed for fludioxonil to evaluate exposures resulting from off-site drift of agricultural products into residential areas.  Incidental exposure to consumers from spray drift from non-residential uses were not included in the aggregate consumer risk; this approach agrees with the EPA's current policy and practice.  The following endpoints were used: a 50 mg/kg/day NOAEL for adults (inhalation only) from a subchronic dog tox study; a 50 mg/kg/day short-term and intermediate-term NOAEL for children 1-6 years (incidental oral) from a subchronic dog tox study.  Residential handler exposure risk from fludioxonil was acceptable (MOE = 11,636; short-term) for youths (13-19 years) and adults (19+ years) treating residential turf with a manually-pressurized handwand.  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, resulting from contact with treated lawns were acceptable (MOE = 4,594) for short-term and intermediate-term durations.  Since the MOEs for children (1-6 years), youths (13-19 years) and adults (19+ years) were above the Benchmark MOE of 100, residential 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 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."  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 produced 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 been established for the U.S. population, so an acute exposure assessment was not performed for the U.S. population.  For short-term exposures, chronic dietary (food and water) exposures were aggregated with residential exposures, resulting in a worse-case short-term aggregate MOE of 2,892 to the U.S. population (Benchmark MOE = 100). The chronic aggregate exposure analysis showed that exposure from all current and proposed fludioxonil uses resulted in a MOE of 5,167 or 1.9% of the cRfD (cRfD=0.33 mg/kg-bw/day) for the general U.S. population, which exceeds the Benchmark MOE of 100.  Based on the completeness and reliability of the toxicity data supporting these petitions, 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 uses of fludioxonil, including anticipated dietary exposure from food, water, and all other types of non-occupational exposures.

	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 analysis showed that exposure from all established and proposed fludioxonil uses resulted in a MOE of 1,625 or 6.2% of the cRfD (Benchmark MOE = 100; cRfD=0.33 mg/kg-bw/day) for children (1-2 years old).  The short-term aggregate assessment resulted in a MOE of 1,600 for the children (1-2 years old) population subgroup (Benchmark MOE = 100).  Since the worst-case aggregate MOE of 2,407 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.

F. International Tolerances

	Codex Maximum Residue Limits (MRLs) for residues of fludioxonil per se have been established on a number of commodities including apple pomace, basil, beans, blackberries, blueberries, broccoli, cabbages, carrot, cereal grains, chives, citrus fruits, cotton seed, cucumber, dewberries, eggplant, grapes, kiwifruit, head lettuce, mango, melons except watermelon, mustard greens, bulb onion, peas, peppers, pistachio nuts, pome fruits, pomegranate, potato, rape seed, raspberries, squash, stone fruits, cereal grains, strawberry, sweet corn, sweet potato, tomato, watercress, yams, and various meat, milk, and egg commodities.




