EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

(10/20/2014)

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:

Syngenta Crop Protection

IN-10775

EPA has received a pesticide petition (IN-10775) from Syngenta Crop 

Protection, P.O. Box 18300, Greensboro, NC 27409 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 §180.910 to establish an exemption from the requirement of a 

tolerance for propylene glycol monomethyl ether (CAS 107-98-2), herein referred to 

in this document as PGME, as an inert ingredient in post-harvest applications 

(40CFR§180.910) without limitation in end-use product formulations. 

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.

EPA recently assessed the science for PGME and summarized the available 

information on the use, physical/chemical properties, toxicological effects, exposure 

profile, environmental fate, and ecotoxicity of this chemical in USEPA (2006a). Inert 

Reassessment – Propylene Glycol Monomethyl Ether (PGME), CAS Reg No. 107-

98-2, issued May 9, 2006. US Environmental Protection Agency, Washington, DC. 

This document is available on the EPA website

(http://www.epa.gov/opprd001/inerts/propylene.pdf).

A. Residue Chemistry
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1. Plant metabolism. No specific plant metabolism data is available, nor is it 

required for the establishment of a tolerance exemption. Plant metabolism is 

anticipated to be similar to that reported for animal metabolism. PGME is rapidly 

metabolized to propylene glycol upon absorption.

2. Analytical method. As this is a petition for a tolerance exemption, an 

analytical method for residues for these compounds on treated agricultural 

commodities is not required.

3. Magnitude of residues. As this is a petition for a tolerance exemption, 

analysis of the magnitude of residues of these compounds on treated agricultural 

commodities is not required. Post-harvest uses of these compounds will not 

significantly affect the dietary risk assessment as presented in the 2006 tolerance 

reassessment document due to similarities with current uses that were demonstrated 

to pass the US EPA dietary risk assessment.

B. Toxicological Profile

1. Acute toxicity. The acute toxicity of PGME is low. Numerous studies have 

been conducted in a variety of species, all of which indicate low toxicity via oral, 

inhalation and dermal exposure.

Acute Toxicity Values for Propylene Glycol Monomethyl Ether

Species Route Value Referencea

Rat Oral LD50 =6100 mg/kg Rowe et al.

Oral LD50 =5710 mg/kg Smyth et al., 1941

Oral LD50 =5200 mg/kg Smyth et al., 1962

Oral LD50 >5000 mg/kg BASF AG, 1979

Oral LD50 =5900 mg/kg BASF AG, 1964

Oral LD50 =10,800 mg/kg Stenger et al.

Oral LD50 =5300 mg/kg Stenger et al.

Oral LD50 >1840 mg/kg BASF AG, 1965

Oral LD50 =9000 mg/kg Shideman and Puscita

Oral LD50 =4600-5500 mg/kg Stenger et al.

Inhalation LC0 >7559 ppm Cieszlak and Crissman

Inhalation LC0 =18,200 mg/m3 Rowe et al.

Inhalation LC0 =36,400 mg/m3 Smyth et al., 1962

Inhalation LC0 =1000 ppm Smyth et al., 1962

Inhalation LC50 =54,600 mg/m3 Rowe et al.

Inhalation LC50 >6000 mg/m3 Gelbke

Inhalation LCL0 =25,200 mg/m3 Gelbke

Inhalation LC50 >24,000 mg/m3 Gelbke

Inhalation LC50 =36,400 mg/m3 Rowe et al.

Mouse Inhalation LC50 >6038 ppm Cieszlak and Crissman

Rabbit Inhalation LCL0 =54,600 mg/m3 Rowe et al.

Guinea Pig Inhalation LC0 =18,750 mg/m3 Rowe et al.
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Inhalation LC50 =54,600 mg/m3 Rowe et al.

Inhalation LC0 =36,400 mg/m3 Rowe et al.

Rabbit Dermal LD50 =13,000 mg/kg Rowe et al.

Dermal LD50 =14,100 mg/kg Smyth et al., a962

 

a All references provided from OECD SIDS, 2001.

2. Genotoxicty. The weight of evidence indicates that PGME is not genotoxic. 

PGME was negative in the Ames test, did not induce unscheduled DNA synthesis, 

sister chromatid exchange or chromosomal aberrations, and was negative when 

tested in a mouse micronucleus assay.

3. Reproductive and developmental toxicity. PGME is structurally related to a 

large group of chemicals collectively known as glycol ethers, some of which (e.g. 

ethylene glycol monomethyl ether) have been shown to cause developmental and 

reproductive effects (especially testicular changes); however, these effects are not 

expected to be seen in PGME because the metabolism is substantially different 

(USEPA, 2006a). The metabolism of ethylene glycol monomethyl ether, a primary 

alcohol, proceeds mainly to methoxyacetic acid, which is considered the toxic 

moiety. PGME does not following this pathway, and instead is converted to 

glucuronide and sulfate conjugates or to propylene glycol, which is further degraded 

to form CO2. As previously noted in the 2006 EPA decision document, studies in 

laboratory animals indicate that PGME is not a developmental toxicant when 

administered via inhalation or ingestion.

4. Subchronic toxicity. The available subchronic data are summarized in the 

EPA decision document posted on the EPA website. Several studies are available 

that adequately represent the subchronic toxicological profile of these compounds]

5. Chronic toxicity. Studies in laboratory animals indicate that PGME is not 

carcinogenic. Rats and mice were exposed to air concentrations of 0, 300, 1000 or 

3000 ppm for up to 2 years. These concentrations resulted in time-weighted average 

dose levels of 0, 310, 1040 and 3120 mg/kg/day in rats and 0, 460, 1540 and 4620 

mg/kg/day in mice. In both species, the highest exposure concentration was chosen 

based on the results of previous subchronic toxicity studies in which sedation, 

hepatic enzyme induction, and increased hepatic cellular proliferation were seen. 

No toxicologically relevant, statistically significant increase in tumors in any tissue 

were observed in male and female rats and mice exposed to PGME via inhalation 

(Spencer et al., 2002). A numerical increase in kidney adenomas in male rats in the 

intermediate exposure level (1000 ppm) was associated with α2-microglobulin 

nephropathy and not relevant to humans. No histopathological changes of 

toxicological significance were noted in any tissue in mice.

6. Animal metabolism. PGME is rapidly absorbed and metabolized to

propylene glycol and ultimately to CO2, and glucuronide or sulphate conjugates.
4

7. Metabolite toxicology. There are no significant concerns regarding the 

toxicity of this compound or potential metabolites.

8. Endocrine disruption. PGME and its metabolites do not appear to disrupt 

(block, enhance, or mimic) normal endocrine function. These compounds are not 

structurally similar to natural hormones, especially estrogens, androgens, and 

thyroid hormones.

C. Aggregate Exposure

1. Dietary exposure. A qualitative aggregate assessment for the pre-harvest 

use of PGME was conducted by the Agency and it was concluded that health 

concerns from food, drinking water, and residential exposures are not anticipated. 

Since this proposed use does not add significant amounts of exposure, these 

conclusions are valid for this petition. Some of the pre-harvest uses covered in the 

previous US EPA assessment have zero-day pre-harvest intervals; under such a use 

pattern, the approved pre-harvest food use would likely result in comparable 

residues from post-harvest applications. Additionally, the post-harvest use of 

PGME will typically be less frequent than the pre-harvest applications which are 

widely used in general agriculture. Therefore, aggregate exposures from the postharvest application use of PGME in pesticide products are expected to result in 

human exposure orders of magnitude below any no observed adverse effect 

observed in the available toxicological studies.

i. Food. The Agency has previously concluded that the primary route of 

exposure to this chemical is possible via dietary consumption (food and/or drinking 

water) or residential (dermal and inhalation) routes of exposure. The qualitative 

aggregate assessment demonstrates that an adequate margin of safety exists for the 

proposed post-harvest extension of these uses.

ii. Drinking water. The requested post-harvest use poses an insignificant 

increment of exposure compared to the already approved and assessed pre-harvest 

uses.

2. Non-dietary exposure. The proposed post-harvest use does not alter 

the exposure as assessed in the 2006 EPA assessment as post harvest treatments take 

place in commercial packing houses.

D. Cumulative Effects

For the purposes of the tolerance reassessment action for PGME, EPA did 

not assume that this chemical has a common mechanism of toxicity with other 

substances.

E. Safety Determination
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1. U.S. population. Post-harvest uses of PGME will not significantly affect the 

dietary risk assessment due to similarities with current uses that pass US EPA 

dietary risk assessment. These resulting residues will not change the conclusions of 

the Agency that PGME uses do not pose unreasonable risk to any population or 

population subgroup or the environment when used according to labeled directions, 

especially considering the low percentage of crops to be treated post-harvest.

2. Infants and children. Taking into account the available information, 

EPA has previously determined that there is a reasonable certainty that no harm to 

any population subgroup will result from aggregate exposure to PGME. This 

conclusion is appropriate for this petition as well.

F. International Tolerances

No Codex maximum residue levels have been established for this compound.