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 Headquarters, 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 establishing a tolerance for residues of the chemical etoxazole, 2-

(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydrooxazole, in or on 

the following raw agricultural commodities: peppers, African eggplant, eggplant, martynia, 

okra, pea eggplant, 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; 

Subgroup 13-07G: 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 15 ppm.

Additionally, the petitioner proposes to delete the established tolerances for strawberry, grape, 

cucumber, and vegetable, 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 adequately understood for the 

purpose of the proposed tolerances.

2. Analytical method. Practical analytical methods for detecting and measuring levels 

of etoxazole have been 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 Register on September 26, 2003 (68 FR 55485)(FRL-7324-8).

C. Aggregate Exposure
1. Dietary exposure. A chronic dietary analysis 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 therefore, the 

assessment has not been repeated to include these minor uses.

The Cumulative and Aggregate Risk Evaluation System (CARES) Version 2.0 was used to 

conduct these assessments. This Tier I assessment used issued and proposed tolerances, 

default processing 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 years 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 years 

old. The c-PAD was defined as the NOEL from a dog chronic oral toxicity study and 

includes an uncertainty 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 is 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 physical 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 and 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 cPAD of 0.046 mg/kg/day for children. Based on this worse case analysis, the contribution of 

drinking water is negligible. 

2. Non-dietary exposure. Etoxazole is proposed only 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 not 

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 out 
to be helpful in eventually determining whether a pesticide shares a common mechanism of 

toxicity with any 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.

 In consideration of potential cumulative effects of etoxazole and other substances that may

have a common mechanism of toxicity, there are currently no available data or other reliable 

information indicating that any toxic effects produced by 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 total 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 safety 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 toxicity

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 uncertainty factor and that an additional 

uncertainty 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 from food to this subgroup is required.

iii. Chronic Risk. The potential chronic exposure from food to children 1-2 years old 

(the most highly 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 

certainty that no harm will result to infants and children from aggregate, chronic exposure to 

etoxazole residues.
F. International Tolerances 

Etoxazole has not been evaluated by the JMPR and there are no codex maximum residue 

limits (MRL) for etoxazole. MRL values have been established for etoxazole in the following 

countries: Turkey, Israel, South Africa, Japan, France, Taiwan, and Korea. The use pattern 

and MRL's are similar to those proposed for the U.S.