EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER ( 10 /2 0 /2014 )

EPA Registration Division contact: William Cutchin

, 703

- 30 5

- 7990

IN STRUCTIONS: 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 petiti on. Simply replace the instructions that appear in green , i.e., “ [ insert

company name ] ,” with the information specific to your action.

TEMPLATE:

Syngenta Crop Protection

I N

- 10775

EPA has received a pesticide petition ( IN

- 10775 ) from Syngenta Crop

Prot ection

, 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 pr opy lene 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 formulation s

.

EPA has determined that the petition contai ns 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 d a ta at this time or whether the data supports granting of the petition. Additional data may be n eeded 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 th is chem ical 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 Chemistry2

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 anima l 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 agricult ural commodities is not requir ed

.

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 affe ct 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 toxici ty 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 Reference a

Rat Oral LD 50 =6100 mg/kg Rowe et al.

Oral LD 50 =5710 mg/kg Smyth et al., 1941

Oral LD 50 =5200 mg/kg Smyth et al., 1962

Oral LD 50 >5000 mg/kg BASF AG, 1979

Oral LD 50 =5900 mg/kg BASF AG, 1964

Oral LD 50 =10,800 mg/kg Stenger et al.

Oral LD 50 =5300 m g/kg Stenger et al.

Oral LD 50 >1840 mg/kg BASF AG, 1965

Oral LD 50 =9000 mg/kg Shideman and Puscita

Oral LD 50 =4600

- 5500 mg/kg Stenger et al.

Inhalation LC 0 >7559 ppm Cieszlak and Crissman

Inhalation LC 0 =18,200 mg/m 3 Rowe et al.

Inhalation LC 0 =36,400 mg/m 3 Smyth et al., 1962

Inhalation LC 0 =1000 ppm Smyth et al., 1962

Inhalation LC 50 =54,600 mg/m 3 Rowe et al.

Inhalation LC 50 >6000 mg/m 3 Gelbke

Inhalation LCL 0 =25,200 mg/m 3 Gelbke

Inhalation LC 50 >24,000 mg/m 3 Gelbke

Inhalation LC 50 =36,400 mg/m 3 Rowe et al.

Mouse Inhalation LC 50 >6038 ppm Cieszlak and Crissman

Rabbit Inhalation LCL 0 =54,600 mg/m 3 Rowe et al. Guinea Pig Inhalation LC 0 =18,750 mg/m 3 Rowe et al.3

Inhalation LC 50 =54,600 mg/m 3 Rowe et al.

Inhalation LC 0 =36,400 mg /m 3 Rowe et al.

Rabbit Dermal LD 50 =13,000 mg/kg Rowe et al.

Dermal LD 50 =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.

PG M E was negativ e 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 CO 2

. As previously noted in the 2006 EPA decision document, studies in laboratory animals indicate that PGME is not a de velopmental 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 toxicolog ical 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 concen trations 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 toxic ity 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 o f toxicological significance were noted in any tissue in mice

.

6. Animal metabolism. PGME is rapidly absorbed and metabolize d to propylene glycol and ultimately to CO2, and glucuronide or sulphate conjugate s

.4

7. Metabolite toxicology

. There are no sign ificant concerns regarding the toxicity of th is 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 simi lar 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

co ncerns 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 fr equent than the pre

- harvest applications which are widely used in general agriculture. Therefore, aggregate exposures from the post

harvest application use of PGME in pesticide products are expected to result in human exposure orders of magnitude below an y no observed adverse effect observed in the available toxicological studies.

i. Food. The Agency has previously concluded that the primary route of exposure to th is 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 in significant 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 pl ace in commercial packing houses

.

D. Cumulative Effects

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

not assume that th is chemical ha s a common mechanism of toxicity with other

substances

.

E. Safety Determination5

1. U.S. pop ulation. 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 u ses 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 a ccount 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. Interna tional Tolerances

No Codex maximum residue levels have been established for th is compound

.