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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: William Cutchin, 703-305-7990

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

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

maintain the outline. Please do not change 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:

Dow AgroSciences L.L.C.

IN-10786

EPA has received a pesticide petition (IN-10786) from DowAgroSciences], 9330 

Zionsville Road, Indianapolis, IN 46268, 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 to establish an exemption from the requirement of a tolerance for propanoic 

acid, 2-methyl-, monoester with 2,2,4-trimethyl-l,3-penfanediol (TMB; CAS no. 25265-

77-4) under 40 CFR 180.910 when used as an inert ingredient as a solvent or co-solvent 

within a pesticidal product.

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

Because an exemption from the requirement of a tolerance is requested, no 

field residue studies are required.

B. Toxicological Profile

1. Acute toxicity. TMB has low acute toxicity in lab animals with oral LD50

values>3200 mg/kg body weight (bw), dermal LD50 values >14000 mg/kg bw and,

inhalation LD50 values > 3.55 mg/L air.

2. Genotoxicty. TMB was negative in the Ames assay and in an in vivo mouse 

micronucleus assay.
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3. Reproductive and developmental toxicity. In a combined repeat dose toxicity 

and developmental and reproductive toxicity screening test in rats, no reproductive or 

developmental toxicity was observed at doses up to 1000 mg/kg bw/day.

4. Subchronic toxicity. In a 15-day oral gavage study in rats, the NOAEL was 

>1000 mg/kg bw/day. In a combined repeat dose toxicity and developmental and 

reproductive toxicity screening test in rats, the NOAEL for systemic toxicity was >1000 

mg/kg bw/day.

5. Chronic toxicity. No chronic toxicity studies were available; however, the lack 

of systemic toxicity in two shorter repeat dose studies at the limit dose of 1000 mg/kg 

bw/day suggests that chronic toxicity is not a concern. QSAR modeling did not indicate 

any concerns for human carcinogenicity.

6. Animal metabolism. TMB is a mixture of the 1-substituted (-65%) and the 3-

substituted (-35%) monoisobutyrate isomers of 2,2,4-trimethyl-l,3-pentanediol. The halflife of the 1-substituted isomer in human and rat blood is between 15 to 22 minutes.

7. Metabolite toxicology. No specific information is available on toxicity of TMB 

metabolites. However, TMB is rapidly metabolized in rat blood, and toxicity of parent 

TMB in rats was not observed at doses up to 1000 mg/kg bw/day, so metabolite toxicity 

is anticipated to be low.

8. Endocrine disruption. TMB does not belong to a class of chemicals known or 

suspected to have adverse effects on the estrogen receptor or endocrine system.

C. Aggregate Exposure

1. Dietary exposure. 

i. Food. An assessment based on the general results of the EPA screening level 

dietary exposure model I-DEEM is provided. I-DEEM is based on a screening level 

dietary assessment of 57 of the most "significant" active ingredients used as surrogates 

for inerts within the Dietary Exposure Evaluation Model software with food Commodity 

Intake Database (DEEM-FCID, Version 3.16). Exposures were compared to a chronic 

reference dose (cRfD) and chronic population adjusted dose (cPAD) of 10 mg/kg bw/day 

based on a NOAEL of >1000 mg/kg bw/day and a 100% uncertainty factor and an FQPA 

safety factor of IX. All exposures were below the cRfD/cPAD and pass the screening 

level dietary risk assessment process for inerts without further refinement.

ii. Drinking water. Drinking water estimates have been included in the I-DEEM 

model and are included in the conclusion of a passing dietary risk assessment as 

discussed above.

2. Non-dietary exposure. No uses of TMB in pesticidal products for non-crop uses 

are indicated in publically available databases. Non-dietary consumer exposures to TMB 

are possible due to its use in formulations of products such as paints, floor finishes, 
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adhesives, and caulks. A risk assessment of consumer exposure through application of 

paint containing TMB inside a residential home revealed acceptable margins of exposure 

(MOEs ), e.g. >100. Aggregate MOEs incorporating both dietary and non-dietary 

exposures were also acceptable (>100).

D. Cumulative Effects

Unlike for pesticides for which EPA has followed a cumulative risk approach 

based on a common mechanism of toxicity, for TMB EPA has not made a common 

mechanism of toxicity finding. Consideration of a common mode of toxicity is not 

appropriate given that there is no information available that indicates potential toxic 

effects, if any, would be cumulative with any other compounds.]

E. Safety Determination

1. U.S. population. Dietary exposures for the US population calculated using IDEEM were all below the cRfD, and MOEs for aggregate exposures, including food and 

drinking water as well as non-dietary exposures from TMB in paints, were acceptable. A 

reasonable certainty of no harm has been established for the general population for the 

proposed use of TMB as an inert ingredient in pesticide formulations.]

2. Infants and children. The available information does not indicate any

qualitative or quantitative evidence of increased susceptibility to infants and children for 

TMB. Therefore no additional safety factor is required for the protection of infants and 

children. Assessment of the various child subpopulations is included in the I-DEEM 

analysis and for all subpopulations, exposures are below the cPAD. Aggregate exposures 

for children, including food and drinking water as well as non-dietary exposures from 

TMB in paints, were acceptable. A reasonable certainty of no harm has been established 

for children as well.

F. International Tolerances

No international tolerances have been established for TMB.