Document ID: EPA-HQ-OPP-2015-0676-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2016-04-25T04:00Z

Notice of Filing

[Valent U.S.A. Corporation]

5F8383

	EPA has received a pesticide petition ([5F8383]) from Valent U.S.A. Corporation, 1600 Riviera Ave., Suite 200, Walnut Creek, CA  94596, in cooperation with Interregional Research Project No. 4 (IR-4), IR-4 Project Headquarters, Rutgers, The State University of Jew Jersey, 500 College Road, East, Suite 201 W, Princeton, NJ  09540, 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 by establishing a tolerance for residues of  ethaboxam ((RS)-N-(α-cyano-2-thenyl)-4-ethyl-2-(ethylamino)-1,3-thiazole-5-carboxamide) in or on the raw agricultural commodities peppers (Pepper/Eggplant Crop Subgroup 8-10B) at 0.6 ppm, cucurbit vegetables (Crop Group 9) at 0.3 ppm, ginseng at 0.09 ppm and potato (Tuberous and Corm Vegetable Subgroup 1C) at 0.01 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 nature of residues in crops is well understood.  Nature of the residue studies (OCSPP Harmonized Guideline 860.1300) were conducted in potato, tomato and grape as representative crops in order to characterize the fate of ethaboxam in all crop matrices.  Two radiocarbon labelling positions were studied in each crop, Thiazole and Thiophene.  The route of metabolism of ethaboxam was similar in the three crop groups, with the extent of metabolism being greater at longer pre-harvest intervals.  Parent ethaboxam was a minor component of the residue in potato, where the majority of radioactive residues were found to be incorporated into glucose and starch.   In tomato, ethaboxam was a major component, with a minor component identified as LGC-35523, an -keto carboxylic acid found only in the Thiophene labelled fruits, and multiple minor polar and other unknowns.  In grape, ethaboxam was a major component, and LGC-35523 was also a significant component, along with multiple minor polar and other unknowns, and some incorporation into sugars.  In the confined crop rotation study, no ethaboxam was found.  There were two major metabolites in the Thiazole label only, EEO and EEHO.  In addition, numerous minor metabolites were present, including some that migrated with sugars during chromatography.  

	2. Analytical method. 
 
 An independently validated analytical method has been submitted for analyzing parent ethaboxam residues with appropriate sensitivity in all crop commodities for which tolerances are being requested.

	3. Magnitude of residues. 
 
 Field trials were carried out to determine the magnitude of the residue in/on peppers, cucumbers, melons, squash, potato and ginseng, and potato processed fractions.  The number and locations of field trials were in accordance with OCSPP Guideline 860.1500.  Field trials were carried out using the maximum label rates, the maximum number of applications, and the minimum pre-harvest interval (PHI) proposed for all the crops.  Tolerances are proposed for peppers (Pepper/Eggplant Crop Subgroup 8-10B) at 0.6 ppm, cucurbit vegetables (Crop Group 9) at 0.3 ppm, ginseng at 0.09 ppm and potato (Tuberous and Corm Vegetable Crop Subgroup 1C) at 0.01 ppm.  There was no concentration of residues into the processed fractions of potato, therefore no separate tolerances are proposed for those fractions.

 Toxicological Profile

A complete, valid and reliable database of mammalian and genetic toxicology studies has been submitted to EPA that supports the proposed tolerances for ethaboxam on peppers (Pepper/Eggplant Crop Subgroup 8-10B), cucurbit vegetables (Crop Group 9), ginseng and potato (Tuberous and Corm Vegetable Subgroup 1C). The toxicological profile for ethaboxam, in support of a petition for ethaboxam tolerances on imported grapes, was published in the Federal Register on September 27, 2006 (71 FR 56388) and in EPA's Pesticide Fact Sheet issued in September, 2006.  Additional information and a current Human Health Risk Assessment for non-food seed treatment uses is available in Docket ID EPA-HQ-OPP-2011-0908. 

Acute toxicity studies for the formulated product V-10208 4 SC Fungicide are being submitted to support the current petitioned uses.  These studies show the formulated product to be of low toxicity by all routes of exposure, and place the formulated product into EPA Toxicity Category IV. 

C. Aggregate Exposure

	1. Dietary exposure.  A Tier 1 dietary exposure assessment from food and water was conducted to evaluate the potential risk due to chronic dietary exposure of the U.S. population and various subpopulations to residues of ethaboxam.  The analysis included the existing grape import MRL (6 ppm) and MRLs for the petitioned uses on ginseng (0.09 ppm), potato (Tuberous and Corm Vegetable Crop Subgroup 1C, 0.01 ppm), peppers (Pepper/Eggplant Crop Subgroup 8-10B, 0.5 ppm), cucurbit vegetables (Crop Group 9, 0.3 ppm) and water (direct and indirect sources, 0.00118 ppm).  

No acute toxicity endpoint is available since ethaboxam is not acutely toxic.  Therefore an acute risk assessment was not conducted.

The ethaboxam chronic toxicity endpoint of 5.5 mg/kg body wt/day is derived from a combined chronic/carcinogenicity study in the rat.  An uncertainty factor of 100 was applied to account for intra- and inter-species variation.  No additional uncertainty factor for FQPA was necessary.  The chronic population adjusted dose (cPAD) is 0.055 mg/kg body wt/day.  Ethaboxam produces Leydig cell tumors in male rats at doses greater than those causing chronic toxicity.  Therefore, the chronic risk assessment was conducted using a non-linear approach, as this adequately covers both chronic toxicity and potential carcinogenicity.

		i. Food.  The potential chronic dietary risk from exposure of the U.S. population and various subgroups to ethaboxam residues in food commodities was assessed using a highly conservative Tier I approach.  This Tier I approach incorporated tolerance level residues and 100% crop-treated in the DEEMTM 4.02 (Dietary Exposure Evaluation Model) software system.  

		ii. Drinking water. Estimated upper-bound drinking water concentrations (EDWC) were determined using USEPA's Surface Water Concentration Calculator version 1.1.06 (SWCC) for surface water exposure modeling.  The maximum chronic surface water EDWC was 1.18 ppb for the U.S. index reservoir based on  a yearly maximum application rate of 0.5 pound active ingredient/acre (lb ai/A) with  0.25 lb ai/A as the maximum rate per application.

	2. Non-dietary exposure.  No non-dietary residential or turf exposures are expected with the petitioned use pattern.

D. Cumulative Effects

FFDCA Section 408(b)(2)(D)(v) requires that the Agency must consider "available information'' concerning the cumulative effects of a particular pesticide's residues and "other substances'' that have a common mechanism of toxicity.  There are currently no available data or other reliable information indicating that ethaboxam shares a common mechanism of toxicity with any other substance.  Only the aggregate exposure of ethaboxam has been considered in this risk assessment.

E. Safety Determination

FFDCA section 408 provides that EPA shall apply an additional margin of safety, up to ten-fold, for added protection for infants and children in the case of threshold effects, unless EPA determines that a different margin of safety will be safe for infants and children.  The toxicological database for evaluating prenatal and postnatal toxicity for S-2200 Fungicide is complete with respect to current data requirements, and there are no special prenatal or postnatal toxicity concerns for infants and children.  This therefore warrants reducing the FQPA Safety Factor for protection of infants and children to 1X.  

      1.  U.S. population.   Based on a highly conservative risk assessment, Valent U.S.A. Corporation concludes that there is a reasonable certainty that no harm will result to the general population from the aggregate exposure to ethaboxam from the proposed uses.  The newly proposed uses of ethaboxam result in an estimated dietary exposure to the U.S. Population equivalent to 6.6% of the cPAD.   Chronic aggregate exposures below 100% of the cPAD are generally considered to represent a reasonable certainty of no harm to exposed populations.

	2. Infants and children.  Based on a highly conservative risk assessment, Valent U.S.A. Corporation concludes that there is a reasonable certainty that no harm will result to infants and children from the aggregate exposure to ethaboxam from the proposed uses.  The most highly exposed subgroup is children 1-2 years of age with an estimated dietary exposure equivalent to 35.6% of the cPAD.  Chronic aggregate exposures below 100% of the cPAD are generally considered to represent a reasonable certainty of no harm to exposed populations. 

 F. International Tolerances
	
There are no CODEX maximum residue levels (MRLs) established or proposed for residues of ethaboxam in for peppers (Pepper/Eggplant Crop Subgroup 8-10B), cucurbit vegetables (Crop Group 9), ginseng and potato (Tuberous and Corm Vegetable Crop Subgroup 1C).  There was no concentration of residues into the processed fractions of potato, therefore no separate tolerances are proposed for those fractions.  There are currently no tolerances for residues of ethaboxam in these crops in Canada or Mexico.