EPA Registration Division contact: Andrew Ertman, (703) 308 - 9367

Interregional Research Project Number 4 (IR- 4) PP #9E7675 EPA has received a pesticide petition ( PP #9E7675 ) from Interregional Research Project Number 4 (IR - 4), IR - 4 Project Headquart ers, Rutgers, The State University of New Jersey , 500 College Road East, Suite 201 W, Princeton, NJ 08450 , 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 .593 , by

estab lishing a toleran ce for residues of the chemical etoxazole, 2 - (2,6 - difluorophen yl ) - 4 - [4 - (1,1 - dimethylethyl) - 2 - ethoxy phen yl ] - 4,5 - dihydrooxazole, in or on the following raw agricultural commodities : peppers , African eggplant, eggplant, mart ynia, okra, pea e ggplant, pepino, roselle, and scarlet eggplant at 0.20 parts per million (ppm) ; Crop Group 9: Cucurbit Vegetables at 0.20 ppm; Subgroup 13 - 07A: Caneberry at 1 . 1 ppm ; Subgroup 13 - 07F: Small fruit vine climbing subgroup except fuzzy kiwi at 0.50 ppm ; Subgrou p 13 - 0 7 G: Low - growing berry subgroup at 0.50 ppm and avocado, papaya, star apple, black sapote, mango, sapodilla, canistel, and mamey sapote at 0.20 ppm ; and tea at 1 5 ppm. Addit i onally , the petitioner proposes to delet e the e stablish ed tolerances for str awberry , grape , cucumber , and v egetable, cucurbit subgroup 9A since they will be covered by

the proposed new tolerances in this action. EPA has determined that the petitions contain data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; 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 etoxazole is adequatel y understood for the purpose of the proposed tolerances. 2. Analytical method. Practical analy tical methods for detecting and measuring levels of etoxazole have be en developed and validated in/on all appropriate agricultural commodities and respective processing fractions. The LOQ of etoxazole in the methods is 0.02 ppm which will allow monitoring of food with residues at the levels proposed for the tolerances. 3. Magnitude of residues . Residue data have been submitted which adequately support the requested tolerance. B. Toxicological Profile The toxicological profile for etoxazole which supports this petition for tolerances was published in the Federal Regist er on September 26, 2003 (68 FR 55485)(FRL - 7324 - 8). C. Aggregate Exposure1. Dietary exposure . A chronic dietary anal ys is was conducted to estimate exposure to potential etoxazole residues in/on the following crops: cotton, fruit, pome (Crop Group 11), strawberry , tangerines, nut, tree (Crop Group 14), pistachios, grapes , hops, and mint. The addition of the proposed uses to the approved uses of etoxazole is expected to make a negligible incremental risk to the dietary risk assessment conducted and theref ore, the assessment has not been repeated to include these minor uses. The Cumulative and Aggregate Risk Evaluation Sy stem (CARES) Version 2.0 was used to conduct these assessments. This Tier I assessment used issued and proposed tolerances, default pro cessing factors, and the assumption of 100% crop treated. No adjustments were made for common washing, cooking or preparation practices. Exposure estimates for water were made based upon modeling ( FIRST and SCI - GROW ). i. Food . a. Acute - An endpoint of concern attributable to a single oral dose was not selected for either the general U.S. population (including infants and children) or the female 13 - 50 y ears old population subgroup. Therefore, quantitation of the acute risk is not required. b. Chronic - The chronic dietary exposure estimate of etoxazole residues in food was calculated to be, at most, 15.2% of the chronic Population Adjusted Dose (c - PAD) with a MOE of 6500. The population subgroup with the highest exposure was children 1 - 2 y ears old. The c - PAD was defined as the NOEL from a dog chronic oral toxicity study and includes an uncertaint y factor of 100 to account for intra - and inter - species variation (NOEL = 4.62 mg/kg bw/day , c - PAD = 0.046 mg/kg/day). ii. Drinking water . Since etoxazole i s applied outdoors to growing agricultural crops, the potential exists for the parent or its metabolites to reach ground or surface water that may be used for drinking water. Because of the ph ys ical properties of etoxazole, it is unlikely that etoxazole or its metabolites can leach to potable groundwater. To quantify potential exposure from drinking water, surface water concentrations for etoxazole were estimated using FIRST and SCI - GROW models. The annual average surface water concentration of etoxazole an d its metabolites was predicted to be 1.77 ppb. Chronic exposure from this drinking water would be 0.0000506 and 0.000177 mg/kg/day for adults and children, respectively ; 0.38% of the c PAD of 0.046 mg/kg/day for children. Based on this worse case anal ys is, the contribution of drinking water is negligible. 2. Non - dietary exposure . Etoxazole is proposed onl y for agricultural uses and no homeowner or turf uses. Thus, no non - dietary risk assessment is needed. D. Cumulative Effects 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 . Available information in this context include no t only toxicity , chemistry , and exposure data, but also scientific policies and methodologies for understanding common mechanisms of toxicity and conducting cumulative risk assessments. For most pesticides, although, the Agency has some information in its files that may turn outto be helpful in eventually determining whether a pesticide shares a common mechanism of toxicity with an y other substances, EPA does not at this time have the methodologies to resolve the complex scientific issues concerning common mechanism of toxicity in a meaningful way . Inconsideration of potential cumulative effects of etoxazole and other substances that may have a common mechanism of toxicity , there are currentl y no available data or other reliable information indicating that any toxic effects produced b y etoxazole would be cumulative with those of other chemical compounds. Thus, only the potential risks of etoxazole have been considered in this assessment of aggregate exposure and effects. E. Safety Determination 1. U.S. population . i. Acute Risk. No acute endpoint has been identified the general U.S. population. Therefore, no assessment of acute exposure from food to this subgroup is required. ii. Chronic Risk. The potential chronic exposure from food to the U.S . Population and various non - child/infant population subgroups will utilize at most 2.8% of the c - PAD. Addition of the worse case, dietary exposure from water (0.0000506 mg/kg/day) has no effect on this exposure. The Agency has no cause for concern if to tal chronic residue contribution is less than 100% of the c - PAD, because the PAD represents the level at or below which daily aggregate exposure over a lifetime will not pose appreciable risk to human health. Therefore, it can be concluded that there is a reasonable certainty that no harm will result to the overall U.S. Population from aggregate, chronic exposure to etoxazole residues. 2. Infants and children . i. Safety Factor for Infants and Children. In assessing the potential for additional sensitivity of infants and children to residues of etoxazole, 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 safet y will be safe for infants and children. The toxicological data base for evaluating prenatal and postnatal toxicity for etoxazole is complete with respect to current data requirements. There are no special prenatal or postnatal t oxicity concerns for infants and children, based on the results of the rat and rabbit developmental toxicity studies or the 2 - generation reproductive toxicity study in rats. EPA has concluded that reliable data support use of the standard 100 - fold uncertai nt y factor and that an additional uncertaint y factor is not needed for etoxazole to be further protective of infants and children. ii. Acute Risk. No acute endpoint has been identified for infants and children. Therefore, no assessment of acute exposure f rom food to this subgroup is required. iii. Chronic Risk. The potential chronic exposure from food to children 1 - 2 y ears old (the most highl y exposed child/infant subgroup) will utilize at most 15.2% of the c - PAD. Addition of the worse case, dietary exposure from water (0.000177 mg/kg/day) increases this exposure to 15.6% of the c - PAD. Therefore, it can be concluded that there is a reasonable certaint y that no harm will result to infants and children from aggregate, chronic exposure to etoxazole residu es.F. International Tolerances

Etoxazole has not been evaluated b y the JMPR and there are no codex maximum residue limits (MRL ) for etoxazole. MRLvalues have been established for etoxazole in the following countries: Turkey , Israel, South Africa, Jap an, France, Taiwan, and Korea. The use pattern and MRL's are similar to those proposed for the U.S.