UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

Date: 28-JUN-2019

SUBJECT: Etoxazole: Human Health Draft Risk Assessment for Registration Review and a Proposed Section 3 Use on Sugar Beets.

PC Code: 107091 DP Barcodes: D449206 and D452124 Decision Nos.: 543452 and 550792 Registration No.: 59639-202 Petition No.: 8E8701 Regulatory Action: Registration Review; Sec. 3 Registration Risk Assessment Type: Single Case No.: 7616 Chemical/Aggregate TXR No.: NA CAS No.: 153233-91-1 MRID No.: NA 40 CFR: §180.593

FROM: Jennifer R. Tyler, Chemist Anwar Dunbar, Ph.D., Toxicologist Sarah J. Levy, Chemist Risk Assessment Branch 1 (RAB1) Health Effects Division (HED; 7509P)

THROUGH: Christine L. Olinger, Branch Chief George F. Kramer, Ph.D., Senior Chemist RAB1/HED (7509P)

TO: Sidney Jackson/Nancy Fitz Risk Management Team 5 Registration Division (RD; 7505P)

Rachel Fletcher/Cathryn Britton Risk Management and Implementation Branch V Pesticide Re-evaluation Division (PRD; 7508P)

The Health Effects Division (HED) is charged with estimating the risk to human health from exposure to pesticides. The Registration Division (RD) has requested that HED evaluate hazard and exposure data and conduct dietary, occupational, residential, and aggregate exposure assessments, as needed, to estimate the risk to human health that will result from the proposed use of etoxazole (2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5- dihydrooxazole)] on sugar beets. Additionally, as part of Registration Review, the Pesticide Reevaluation Division (PRD) has requested that HED evaluate the hazard and exposure data and conduct dietary, occupational, residential, and aggregate exposure assessment, as needed, to estimate the risk to human health that will result from all the currently registered uses of etoxazole.

Page 1 of 42 Etoxazole Human Health Risk Assessment DP Nos. 449206 and 452124 This memorandum serves as HED’s draft human health risk assessment of the dietary, occupational, and residential exposure and aggregate risk from the registered and proposed uses of etoxazole. The hazard characterization and endpoint selection were provided by Anwar Dunbar; the risk assessment and occupational and residential exposure assessment were provided by Jennifer Tyler; and the residue chemistry and dietary exposure assessments were provided by Sarah Levy. The drinking water assessment was provided by José Meléndez of the Environmental Fate and Effects Division (EFED).

Page 2 of 42 Etoxazole Human Health Risk Assessment DP Nos. 449206 and 452124

Table of Contents 1.0 Executive Summary ...... 4 2.0 Risk Assessment Conclusions ...... 7 2.1 Tolerance Considerations ...... 8 2.2 Label Recommendations ...... 10 3.0 Introduction ...... 11 3.1 Chemical Identity ...... 11 3.2 Physical/Chemical Characteristics ...... 11 3.3 Pesticide Use Pattern ...... 11 3.4 Anticipated Exposure Pathways ...... 14 3.5 Consideration of Environmental Justice ...... 15 4.0 Hazard Characterization and Dose-Response Assessment ...... 15 4.1 Toxicology Studies Available for Analysis ...... 15 4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ...... 16 4.3 Toxicological Effects ...... 16 4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ...... 17 4.5 Toxicity Endpoint and Point of Departure Selections ...... 18 4.6 Endocrine Disruptor Screening Program ...... 20 5.0 Dietary Exposure and Risk Assessment ...... 21 5.1 Residues of Concern Summary and Rationale ...... 21 5.2 Food Residue Profile ...... 22 5.3 Water Residue Profile ...... 23 5.4 Dietary Risk Assessment ...... 24 6.0 Residential Exposure/Risk Characterization...... 25 7.0 Aggregate Exposure/Risk Characterization ...... 25 8.0 Non-Occupational Bystander Post-Application Inhalation Exposure and Risk Estimates 25 9.0 Non-Occupational Spray Drift Exposure and Risk Estimates ...... 25 10.0 Cumulative Exposure/Risk Characterization ...... 27 11.0 Occupational Exposure/Risk Characterization ...... 28 11.1 Occupational Handler Exposure and Risk Estimates ...... 28 11.2 Occupational Post-Application Exposure and Risk Estimates ...... 34 12.0 Incident and Epidemiological Data Review ...... 35 Appendix A. Toxicology Profile and Executive Summaries ...... 36 Appendix B. Physical/Chemical Properties ...... 40 Appendix C. International Residue Limit Status Sheet...... 41

Page 3 of 42 Etoxazole Human Health Risk Assessment DP Nos. 449206 and 452124 1.0 Executive Summary

RD requested that HED conduct a human health risk assessment for the proposed new use of etoxazole on sugar beets. Additionally, as part of Registration Review, PRD has requested that HED evaluate the hazard and exposure data and conduct dietary, occupational, residential, and aggregate exposure assessment, as needed, to estimate the risk to human health that will result from the currently registered uses of etoxazole.

Use Profile: Etoxazole is a contact acaricide/ovicide and is a member of the diphenyloxazoline class of insecticide/miticide.

Proposed New Use (PP#8E8701): The petition, submitted by the Interregional Research Project Number 4 (IR-4), in association with the registrant Valent U.S.A. Corporation, includes the addition of sugar beets to the Zeal® SC Miticide label (EPA Reg.# 59639-202; revised label submitted by IR-4, dated 13-MAY-2019, L. Obrestad to M. Lewis). This product is formulated as a soluble concentrate (SC) packaged in a water-soluble package (WSP) and can be applied as a foliar broadcast application at a maximum rate of 0.135 pounds (lb) active ingredient (ai)/A via ground or aerial equipment. The proposed pre-harvest interval (PHI) is 30 days.

Registered Uses: Etoxazole is currently registered for use on a variety of crops and ornamentals as well as for use in commercial greenhouses. The current registrations also include Special Local Need (SLN) registrations on carrots and alfalfa. Etoxazole is formulated as wettable powders (WPs) packaged in WSPs, water-dispersible granules (WDGs), SCs, pressurized liquids, and pressurized gases. Permanent tolerances are established for residues of etoxazole in/on a variety of crops and livestock commodities at levels ranging from 0.01 ppm to 20 ppm (40 CFR §180.593 (a)). There are currently no tolerances established for etoxazole for indirect/inadvertent residues in rotational crops.

The registered and proposed product labels require applicators and other handlers to wear personal-protective equipment (PPE) which consists of long-sleeved shirt, long pants, shoes plus socks, and chemical resistant gloves made of waterproof material. The restricted-entry interval (REI) for all uses is 12 hours.

Exposure Profile: Humans may be exposed to etoxazole in food and drinking water since etoxazole may be applied directly to growing crops and application may result in etoxazole reaching surface and ground water sources of drinking water. There are no residential uses of etoxazole, so there is not likely to be exposure in residential settings. However, there is potential for non-occupational spray drift exposure. In an occupational setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is a potential for post-application exposure for workers re-entering treated fields. This risk assessment considers all of the aforementioned exposure pathways based on the registered and proposed uses of etoxazole.

Hazard Assessment: The effects in the etoxazole database show liver toxicity in all species tested (enzyme release, hepatocellular swelling and histopathological indicators), and the severity does not appear to increase with time. In rats only, there were effects on incisors (elongation, whitening, and partial loss of upper and/or lower incisors). There is no evidence of neurotoxicity or immunotoxicity. No toxicity was seen at the limit dose in a 28-day dermal toxicity study in rats. Etoxazole was not mutagenic. No increased