EPA REGISTRATION DIVISION CO MPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [P.V. Shah, 703-308-1846]

INSTRUCTIONS: Please utilize this outline in p reparing the pesticide petition. In

cases where the outline element does not apply, please insert “NA-Remove” and

maintain the outline. Please do not chan ge the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green , i.e., “ [insert company name] ,” with the information specific to your action.

TEMPLATE:

Bayer CropScience

[Insert petition number]

EPA has received a pesticide petition (PP# 9E7580) from Bayer CropScience, 2 T.W. Alexander Drive, P.O. Box 12014, Research Triangle Park, NC 27709 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 180.920.

(Options (pick one)

1. by establishing a tolerance for residues of

2. to establish an exemption from the requirement of a tolerance for α -isotridecylω -methoxy-poly(oxy-1,2-ethanediyl), CAS# 345642-79-7 when used as a surfactant in pesticide formulations in or on all raw agricultural commodities . 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. No plant metabolism studies have been submitted in support of this petition since an exemptio n from the requirement of a tolerance is being requested.

2. Analytical method. S ince the petitioner is request ing a tolerance exemption,2

an analytical method for residues of th e inert in food crops is not required.

3. Magnitude of residues. There is no specific crop residue information is

available for α -isotridecyl- ω -methoxy-poly(oxy-1,2-ethanediyl) and this information is typically not available nor required for th e establishment of a tolerance exemption for inert ingredients.

B. Toxicological Profile

Toxicology data have been generated for α -isotridecyl- ω -methoxy-poly(oxy-1,2- ethanediyl) and are representative for the commercial product.

1. Acute toxicity. α -isotridecyl- ω -methoxy-poly(oxy-1,2-ethanediyl) shows low toxicity (Cat. III) via oral and dermal routes of exposure but is considered irritating to skin and eyes, and a dermal sensitizer.

2. Genotoxicty. No evidence of mutagenicity was observed with α -isotridecylω -methoxy-poly(oxy-1,2-ethanediyl) in two i ndependent Ames assays under any of

the test conditions.

3. Reproductive and developmental toxicity. The toxicity of α -isotridecyl- ω

methoxy-poly(oxy-1,2-ethaned iyl) was assessed according to the OECD 422 study design. Wistar rats were exposed for 40 days to the test material in deionized water by oral gavage at 0, 45, 150, or 300 mg/kg/day. Reproductive performance and litter parameters were comparable among all dose groups. The reproductive and offspring No Observed Adverse Effect Level was 300 mg/kg/day.

4. Subchronic toxicity. The toxicity of α -isotridecyl- ω -methoxy-poly(oxy-1,2- ethanediyl) was assessed according to the OECD 422 study design. Wistar rats were exposed for 40 days to the test material in deionized water by oral gavage at 0, 45, 150, or 300 mg/kg/day. Clinical signs were observed at 150 and 300 mg/kg/day and consisted primarily of oral and urine staini ng and salivation. Body weight gain and food consumption were statistically reduced during the first week of treatment only for males at 300 mg/kg/day. No treatment-rel ated changes were observed in clinical chemistry, hematology, or urinalysis para meters. Neurological evaluations showed findings attributable to treatment in fe males only at 150 and 300 mg/kg/day. In addition, females at 300 mg/kg/day ex hibited a significantly lower body temperature. At necropsy, absolute and relative liver and adrenal weights were increased in females at 300 mg/kg/day. However, microscopic changes were not observed in either of these organs. Micro scopic findings attributable to the test material were limited to the non-glandular epithelium of the stomach and consisted of epithelial hyperplasia in the majori ty of males and several females at 300 mg/kg/day and in one female at 150 mg/kg/ day. Other related microscopic findings at 300 mg/kg/day in the non-glandular epithelial included acanthosis, edema, hyperkeratosis and acute inflammation. Th e NOAEL for parental systemic toxicity was 45 mg/kg/day.

5. Chronic toxicity. No chronic studies are available.3

6. Animal metabolism. All ethers undergo peroxidation via auto-oxidation mechanism by the addition of one molecule of oxygen. The normal ether peroxide undergoes spontaneous decomposition and the principal products are acid and

alcohol. The oxidation take s place preferentially at the α -carbon. In the case of

α -isotridecyl- ω -methoxy-poly(oxy-1,2-ethanediyl), the oxi dation is very likely to take place preferentially at th e methyl group. The methyl carbon is also at the α -position to the oxygen. Thus, the major oxidative product is anticipated to be the demethylated product. Accordin gly, the primary metabolite of α -isotridecyl- ω

methoxy-poly(oxy-1,2-ethaned iyl) (CAS# 345642-79-7) is anticipated to be α

isotridecyl- ω -hydroxy-poly(oxy-1,2-etha nediyl) (CAS# 9043-30-5).

in silico evaluation of the predicted mammalian metabolism of α -isotridecylω -methoxy-poly(oxy-1,2-ethanediyl), as pr ovided by the Meteor program (Lhasa Ltd, UK) was conducted. Meteor program uses expert knowledge rules in metabolism to predict the metabolic fate of chemicals. Formation of α -isotridecyl- ω

hydroxy-poly(oxy-1,2-ethanediyl) via oxidative O-demethylat ion being indicated as the first step of the biotransformation scheme.

7. Metabolite toxicology

. The primary metabolite of α -isotridecyl- ω -methoxypoly(oxy-1,2-ethanediyl) (CAS# 345642- 79-7) is anticipated to be α -isotridecyl- ω

hydroxy-poly(oxy-1,2-ethanediyl) (CAS# 9043- 30-5) which has been reassessed by the EPA as a part of the Joint Inerts Ta sk Force Cluster Support Team Number 1 and exempted from tolerance for pre- and po st-harvest uses, application to animals, use in anti-microbial formulations (food su rface sanitizing solutions) and polymers (Federal Register, Vol. 74, No. 149, Au gust 5, 2009, pp. 38935-38944). Thus, the EPA has already reached the conclusion that Cluster 1 of alkyl alcohol alkoxylates, including α -isotridecyl- ω -hydroxy-poly(oxy-1,2-ethanediyl), will not cause harm to

human health or the environment.

8. Endocrine disruption

. Based on the information obtained during an OECD 422 study with α -isotridecyl- ω -methoxy-poly(oxy-1,2-ethanediyl), there is no evidence of endocrine disruption by this co mpound when used as an inert ingredient in pesticide formulations

.

C. Aggregate Exposure

1. Dietary exposure. The use pattern for α -isotridecyl- ω -methoxy-poly(oxy1,2-ethanediyl) is expected to result in exposure to the general population through food and drinking water. The NOAEL of 45 mg/kg/day from the OECD 422 study is selected as the point of departure for all risk assessments. Applying a 100X uncertainty factor for interspecies extrap olation and intraspecies variability, the cRfD is 0.45 mg/kg/day.

i. Food. In the absence of actual dietary exposure data, a chronic dietary exposure analysis was performed using EP A’s screening model for inert compounds4

(DEEM FCID Version 2.0, 1994-1996, 98 CSFII) assuming 100% crop treated for over 500 commodities (raw and processed) including livestock, milk and eggs, highest residue values used based on 57 acti ve ingredients, and no adjustments for percentage of inert in formulations.

ii. Drinking water. The model used for assessing dietary exposure includes a worst case assumption of 0.1 ppm in water.

2. Non-dietary exposure

. Residential uses are currently not considered.

D. Cumulative Effects

No information is available indicating that α -isotridecyl- ω -methoxypoly(oxy-1,2-ethanediyl) has a common mechanism of toxicity with other

substances.

E. Safety Determination

1. U.S. population. Using the assumptions and data described above, it is concluded that chronic dietary exposure to α -isotridecyl- ω -methoxy-poly(oxy-1,2- ethanediyl) uses as inert ingredients in pe sticide formulations will utilize at most 27 % of the chronic PAD for the US Population. The actual exposure is likely to be

much less as the calculations is based on very conservative assumptions. EPA generally has no concern for exposures belo w 100% of the PAD. Therefore, there is a reasonable certainty that no harm will occur to the US Population from aggregate exposure (food and drinking water) to residues of α -isotridecyl- ω -methoxypoly(oxy-1,2-ethanediyl) when used as an in ert ingredient in pesticide formulations.

2. Infants and children

. Based on this information obtained in an OECD 422 study, there is no concern for increased sensitivity to infants and children to α

isotridecyl- ω -methoxy-poly(oxy-1,2-ethanediyl). Therefore, an additional safety factor for the protection of infants and children is unnecessary. Using the assumptions and data described in the exposure section above, the percent of the chronic PAD that will be used for exposure to residues of α -isotridecyl- ω -methoxypoly(oxy-1,2-ethanediyl) in food and drin king water for Children 1-2 years old (the most highly exposed sub-population) is 94.1 %. Infants utilize 54.7 % of the chronic PAD. The actual exposure is likely to be much less as the calculations is based on very conservative assumptions. EPA generally has no concern for exposures below 100% of the PAD. Therefore, there is a reasonable certainty that no harm will occur to infants and children from aggregate exposure to residues of α -isotridecylω -methoxy-poly(oxy-1,2-ethanediyl) when used as an inert ingredient in pesticide

formulations.

F. International Tolerances

No international maximum residue lim its (MRL) or CODEX tolerances are

known to have been established for α -isotridecyl- ω -methoxy-poly(oxy-1,2-5

ethanediyl).