Document ID: EPA-HQ-OPP-2019-0230-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2019-08-05T04:00Z

Notice of Filing

EPA Registration Division contact: Lindsay Roe, (703)347-0506

[Valent U.S.A. LLC]

9F8747

	EPA has received a pesticide petition ([9F8747]) from Valent U.S.A. LLC, 1600 Riviera Ave., Suite 200, Walnut Creek, CA  94596, 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 commodity "beet, sugar, root"  at 0.01 mg/kg (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 formed through natural incorporation of [14]C via sugars and other primary metabolites.  

	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. 
 
 A rationale along with magnitude of residue data for sugar beet roots from 17 locations have been submitted, which adequately support the requested tolerance.  Field trials were carried out using the maximum label rate.  No residues were observed at or above the LOQ of 0.01 mg/kg, so a tolerance is proposed for beet, sugar, root at 0.01 mg/kg.  Residues in sugar beet roots grown from seed treated at a 5X rate were <0.01 mg/kg, and residues in the sugar beet processed fractions were <0.01 mg/kg, so no separate tolerances are proposed for the processed 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 "beet, sugar, root". 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 are available in Docket ID EPA - HQ - OPP - 2015 - 0676. The nature of the toxic effects caused by ethaboxam, as well as the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL) from the toxicity studies reviewed, are discussed in the Federal Register/Vol 82, No.148/August 3, 2017 (36086-36090).  https://www.govinfo.gov/content/pkg/FR-2017-08-03/pdf/2017-16371.pdf .

C. Aggregate Exposure

	1. Dietary exposure.  A Tier 1 dietary exposure assessment from food and water were conducted by EPA to evaluate the potential risk due to chronic dietary exposure of the U.S. population and various subpopulations to residues of ethaboxam. Residues from use of ethaboxam on sugar beet as seed treatment were not included in the current assessment because the contribution to the overall aggregate exposure is considered negligible. These crop residues will be included in the aggregate exposure assessment at a later date. 

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 for existing foliar uses with USEPA's Pesticide in Water Calculator (PWC) version 1.50 for surface water, and Pesticide Root Zone Model Ground Water (PRZM GW) for ground water exposure modeling.  The maximum chronic surface water EDWC was 3.91 ppb for surface water and 7.4 ppb for ground water.  The contribution of seed treatment uses is negligible.

	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 Ethaboxam 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. LLC 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.  

	2. Infants and children.  Based on a highly conservative risk assessment, Valent U.S.A. LLC 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. EPA has concluded that chronic exposure to ethaboxam from food and water will utilize 36% of the cPAD for children 1 - 2 years old, the population group receiving the greatest exposure.

 F. International Tolerances
	
There are no CODEX maximum residue levels (MRLs) established or proposed for residues of ethaboxam in sugar beet root.  There are currently no tolerances for residues of ethaboxam in this crop in Canada or Mexico.