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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE

PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: M. Dow , 703

- 30 5

- 5533

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

re place the instructions that appear in green , i.e., “ [ insert company name ] ,” with the information specific to your action.

TEMPLATE:

Ecolab, Inc.

[ IN

- 10525 ]

EPA has received a pesticide petition ( [ IN

- 10525 ] ) from Ecolab, Inc., EPA Company Number 1677, 370 N. Wabasha Street, St. Paul, MN 55102 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.

( Options (pick one)

2. to establish an exemption from the requirement of a tolerance for

Propylene Glycol, CAS No. 57

- 55

- 6 for use as an inert ingredient in antimicrobial pesticide formulations applied to food

- contact surfaces in public eating places, dairy processing equipment and food processing equipment and utensils in acco rdance with 40 CFR §180.940(a)

. 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 befo re EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. Not applicable to this inert ingredient petition

.

2. Analytical method. Not applicable to this inert ingredient petition

.

3. Magnitude of residues. Not applicable to this inert ingredient petition

.2

B. Toxicological Profile

1. Acute toxicity. Propylene glycol is shown to be of low acute toxicity. Acute Oral LD 50 values ranged from 8,000 mg/kg to >20,000 mg/kg and Acute Dermal LD 50 values are greater than 20,000 mg/kg (EPA Toxicity Category IV)

. It is not an eye or skin irritant and is not a skin

sensitizer.

2. Genotoxicty. Propylene glycol has been tested for mutagenic or genotoxic potential and previously found to be negative by EPA in a battery of studies: a bacterial gene mutation assay using Salmonella typhimurium , and in vitro Chinese hamster ovary (CHO) mutation

assay, an in vitro Chinese hamster ovary (CHO) chromosomal aberration assay and an in

vitro sister chromatid exchange assay.

3. Reproductive and developmental toxicity. The toxicological database utilized by EPA for propylene glycol was comprised of published and unpublished studies either submitted to the Agency or obtained directly from the open literature. The Agency determined that the toxicological database was sufficient for reregistration and reassessment decisions and n o toxicological endpoints of conc ern were identified. Additionally, UNEP concluded that propylene glycol is not a reproductive or developmental toxicant with NOELs in rats, mice, rabbits, or hamsters ranging from 1.2 to 1.6 g/kg bw/day in all four species.

4. Subchronic toxicity. The toxicological database utilized by EPA for propylene glycol was comprised of published and unpublished studies either submitted to the Agency or obtained directly from the open literature. The Agency determined that the toxicological database was

sufficien t for reregistration and reassessment decisions. No toxicological endpoints of concern

were identified.

5. Chronic toxicity. The toxicological database utilized by EPA for propylene glycol was comprised of published and unpublished studies either submit ted to the Agency or obtained directly from the open literature. The Agency determined that the toxicological database was sufficient for reregistration and reassessment decisions. EPA concluded that propylene glycol was negative for carcinogenicity in st udies conducted up to the testing limit doses established by the Agency; therefore, no further carcinogenic analysis was required. UNEP indicates that a 2

- year repeat dose exposure study in rats to propylene glycol in drinking water and feed did not

resul t in adverse effects at levels up to 10% in water (about 10 g/kg bw/day) or 5% in feed (about 2.5 g/kg bw/day). A 2

- year rodent carcinogenicity study showed that propylene glycol is not a carcinogen, with no increase in tumors when administered in the die t (2.5 g/kg bw/day for 2 years) or applied to skin of female rats for 14 months, or mice (2 g/kg bw/week; lifetime).

6. Animal metabolism. Propylene glycol should be readily metabolized to lactic acid at the typical low

- level exposures associated with the already approved pesticide inert ingredient registrations under 40 CFR §180.910 and 40 CFR §180.930 uses and the intended 40 CFR §180.940(a)

. At higher co ncentrations (absorbed doses), propylene glycol is primarily excreted unchanged in the urine.3

7. Metabolite toxicology

. The toxicological database utilized by EPA for propylene glycol was comprised of published and unpublished studies either submitted to the Agency or obtained directly from the open literature. Although not all available studies met the requirements of the Agency’s OPPTS harmonized test guidelines published in 1998, EPA determined that these studies contained useful information adequate f or hazard characterization of propylene glycol. These acceptable non

- guideline studies included acute, subchronic, chronic, developmental, and reproductive toxicity, carcinogenicity, mutagenicity, metabolism/pharmacokinetics and dermal absorption studies. The Agency determined that the toxicological database was sufficient for reregistration and reassessment decisions.

8. Endocrine disruption

. EPA did not report having any available information to suggest that propylene glycol would have any endocrine ef fects. When the appropriate screening and/or testing protocols under the EDSP have been developed, propylene glycol may be subject to additional screening and/or testing to better characterize effects related to endocrine disruption. This does not impact the current regulatory status of propylene glycol.

C. Aggregate Exposure

Upon review of the available toxicity information, the Agency has previously concluded that there were no endpoints of concern for oral, dermal, or inhalation exposure to propylene glycol. This conclusion was based on the results of toxicity testing of propylene glycol in which dose levels were near or above testing limits (as established in the OPPTS 870 series harmonized test guidelines) in experimental animal studies and no signif icant toxicity was observed.

1. Dietary exposure. R isk estimates have not previously been calculated by EPA for potential exposures to propylene glycol on food or drinking water because there are no toxicological endpoints of concern according to a review of the available toxicity data.

i. Food. R isk estimates have not previously been calculated by EPA for potential exposures to propylene glycol on food because there are no toxicological endpoints of concern according to a review of the available toxicity data.

ii. Drinking water

. R isk estimates have not previously been calculated by EPA for potential exposures to propylene glycol in drinking water because there are no toxicological endpoints of concern according to a review of the available toxicity data.4

2. Non

- dietary exposure

. R isk estimates have not previously been calculated by EPA for potential exposures to propylene glycol as a result of use in residential settings because there are no toxicological endpoints of concern according to a review of the available toxicity data.

D. Cumulative Effects EPA has not made a common mechanism of toxicity finding for propylene glycol.

E. Safety Determination

1. U.S. population. As part of the FQPA tolerance reassessment process, EPA concluded

that there are no toxicity endpoints of concern for oral, dermal, or inhalation exposure to propylene glycol. This conclusion was based on the results of toxicity testing of propylene glycol in which dose levels near or above testing limits (as established in the OPPTS 870 series

h armonized test guidelines) were employed in experimental animal studies and no significant toxicity observed. The Agency determined that the established exemptions from the requirement for a tolerance for propylene glycol for current uses met the safety st andards under the FQPA amendments to section 408(b)(2)(D) of the FFDCA, and that there is a reasonable certainty no harm will result to the general population or any subgroup from the use of propylene glycol. In reaching this conclusion, the Agency has con sidered all available information on the toxicity, use practices and exposure scenarios of propylene glycol.

Because no toxicological endpoints were identified for propylene glycol, EPA previously determined that exposure to it does not result in human h ealth effects of concern. Therefore, a quantitative risk assessment was deemed not necessary

.

2. Infants and children

. EPA has removed the FQPA Safety Factor (i.e., reduced to 1X) for propylene glycol, because there is no pre

- or post

- natal evidence fo r increased susceptibility following exposure. Thus, the Agency determined that the established exemptions from the requirement of a tolerance for propylene glycol for the current uses in 40 CFR §180.910 and §180.930 formulations meet the safety standards under the FQPA amendments to section 408(b)(2)(D) of the FFDCA. Moreover, there is a “reasonable certainty no harm” will result to the general population, or any sensitive subgroup, from the use of propylene glycol as an active ingredient or as an inert i ngredient in pesticide formulations. In reaching this conclusion, as noted in the 2006 RED, EPA considered all available information on the toxicity, use practices and exposure scenarios of propylene glycol.

F. International Tolerances Currently there are no Codex MRLs established for propylene glycol.