# i

EPA REGISTRATION DIVISION COMPANY 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 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. ]

1E7936

EPA has received a pesticide petition ( 1E7936 ) from Exponent on behalf of Ecolab, Inc. (Ecolab, EPA Company Number 1677) ]

, [ 370 N. Wabasha Street, St. Paul, Minnesota, 55102 ] request ing, 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 requir ement of a tolerance for Sodium Xylene Sulfonate (SXS, CAS

# 1300

- 72

- 7) under 40 CFR 180.940(a) 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 at 500 parts per million (ppm). EPA has determined t hat 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/Not required for the establishment of a tolerance exemption for inert ingredients.]

2. Analytical method. [ Not applicable/Not required for the establishment of a tolerance exemption for inert ingredients. ]

3. Magnitude of residues. [ Not applicable/Not required for the establishment of a tolerance exemption for inert ingredients. ]

B. Toxicological Profile2

1. Acute toxicity. [ The acute toxicity data indicate that the hydrotropes category

described in the OECD SIDS Assessment , which includes SXS, has a low hazard potential. Acute oral LD 50 values for rats range from 1,044 mg a.i./kg bw, (calcium xylene sulfonate) to 6,480 mg a.i./kg bw (sodium xylene sulfonate). The acute dermal

LD 50 value was >2000 mg/kg bw (624 mg a.i./kg bw following 24 hr exposure). The

inhalation LC 50 in rats was > 557 mg/L. Overall, hydrotropes, and therefore SXS, demonstrate a relatively low order of acute oral and dermal toxicity. The hydrotropes category is considered to have a low skin and eye irritation potential. Sodium xylene

sulfonate was not found to be a skin irritant. ]

2. Genotoxicty. [ The hydrotropes category, including SXS, has been assessed for mutagenic /genotoxic potential in a variety of in vivo and in vitro assays , specifically: mouse micronucleus assays with calcium xylene sulfonate and sodium cumene sulfonate, an Ames assay, mouse lymphoma, sister chromatid exchange, and chromosome aberration assay with SXS , an Ames assay with calcium xylene sulfonate and an Ames assay with sod ium cumene sulfonate. EPA has previously concluded that there were no positive results in the in vitro or in vivo genotoxicity studies , and that there was no evidence of carcinogenic potentia l for both mice and rats dermal l y exposed for two

years

. ]

3. Re productive and developmental toxicity. [ There are no reproductive toxicity studies reported for hydrotropes. However, EPA concluded that the 91

- day oral rat feeding study with sodium cumene sulfonate, the 90

- day feeding study with SXS, and the

2

- year dermal stud y with SXS included examination of the reproductive organs of both

sexes and there is no evidence to suggest that SXS would h ave an advers e effect on reproductive organs

.

No developmental effects or maternal toxicity were observed in a developmental toxicity study in rats conducted with calcium xylene sulfonate

. T he NOAEL for maternal and fetal toxicity was set at the highest dose tested

, 3000 mg/kg bw/day or 936 mg a.i./kg bw/day. Based on this OECD guideline study

, hydrotropes, including SXS, are not considered to be developmental toxicants. ]

4. Subchronic toxicity. There are several oral and dermal repeat dose subchronic

s tudies. EPA has previously concluded that no significant systemic toxicity was noted in the dermal studies. The most appropriate NOAEL for local effects was determined to be 440 mg a.i./kg bw based on epidermal hyperplasia at the site of application (dermal exposure) in male mice.

EPA determined that the most appropriate NOAEL for systemic toxicity from the oral subchronic studies was 763 mg/kg bw/day from a 90

- day rat oral toxicity study. Effects observed in this study were a decrease in spleen weight in females along with some clinical chemistry and hematology changes. No adverse effects were reported in males. ]

5. Chronic toxicity. [ Chronic toxicity/carcinogenicity data for rats and mice dermally exposed to SXS for two years showed n o treatment related effects with the exception of epidermal hyperplasia at the application site in female rats at 120 and 2403

mg. Based on these data , EPA concluded that there was no evidence of carcinogenic potential for SXS. ]

6. Animal metabolism. [ There are no adsorption, distribution, metabolism and

elimination studies for the hydrotropes category identified in the OECD SIDS

Assessment . However, based on available physicochemical properties of the hydrotropes (molecular weight of 194

- 226, water solubility of 553 g/L and octanol/water partition coefficient (Log P) value of

– 2.7) and available toxicological information, the OECD

SIDS Ass essment made qualitative comments regarding absorption

, conclud ing that the available data suggest that absorption will be significantly greater following oral exposure as compared to dermal exposure .]

7. Metabolite toxicology

. [ No metabolites of toxicological concern are expected .]

8. Endocrine disruption

. [ SXS does not belong to a class of chemicals known or suspected of having adverse effects on the estrogen receptor or endocrine system. SXS in association with the structurally similar compou nds included in the OECD Hydrotropes Category have been evaluated in acute, repeated dose, developmental, and chronic toxicity studies capable of detecting effects on endocrine mediated events. ]

C. Aggregate Exposure

1. Dietary exposure. [ Dietary (food and drinking water) and residential (dermal and inhalation) exposures are possible from the use of SXS as an inert ingredient in antimicrobial formulations. SXS is predicted to be readily biodegradable, which will

reduce the likelihood of residues on food. For the same reason EPA did not anticipate significant contributions to drinking water from the use of hydrotropes as inert ingredients in pesticide products. Hydrotropes have low toxicity and exposure to residues

a bove toxicity levels of concern are not anticipated.

The proposed chronic Population Adjusted Dose (cPAD) for SXS is 7.63 mg/kg/d based on the NOAEL of 763 mg/kg/d for reduction in relative spleen weight in female rats from

a 90

- day oral toxicity study. The standard 10X uncertainty factors f or inter

- and intra

species extrapolation are applied to calculate the cPAD.

A dietary risk assessment was conducted using the proposed use pattern for SXS as an inert ingredient in antimicrobial formulations. Conservatively estimated potential SXS dietary exposures resulting from the use of sanitizing solutions containing SXS are very low even when all potential sources are considered. Total exposure estimates reported

are 0.0 6 1% of the cPAD for adult males, 0.0 7 1% of the cPAD for adult females and

0. 2 8% of the cPAD for children. ]

i. Food. [ Exposures are well below 100% of the cPAD, and are therefore below EPA’s established level of concern for all U.S. subpopulations .]

ii. Drinking water

. [ D ietary and residential exposures are possible from the use of

SXS as an inert ingredient in pesticide products. Hydrotropes are predicted to be readily4

biodegradable according to OECD criteria, which will reduce the likelihood of residues

on food. For the same reason, EPA did not anticipate significant contributions to drinking water from these chemicals as inert ingredients in pesticide formulations applied to growing crops and animals. Exposures to residues above toxicity levels of concern are not anticip ated. ]

2. Non

- dietary exposure

. [ The greatest non

- dietary exposure to the consumer was considered dermal exposure following use of personal care products, typically diluted during use and then rinsed off. Dermal contact may also occur with laundry and/or cleaning products. There is some potential for incidental / accidental ingestion of, and/or eye contact with, product during handling and use. Low volatility minimizes the potential

for inhalation. Given the low estimate of dietary exposure from uses of S XS in antimicrobial formulations, there is ample room in the overall aggregate MOE to conservatively account for non

- dietary uses of SXS. ]

D. Cumulative Effects

[ EPA previously assumed that hydrotropes do not have a common mechanism of toxicity with oth er substances. For the purpose of the tolerance exemption action cited herein, Ecolab has assumed that SXS will not have a common mechanism of toxicity

with other substances. ]

E. Safety Determination

1. U.S. population. [ Based on the conservative exposure estimates, there is a reasonable certainty that no harm will result to the U.S. population from the aggregate exposure to SXS ]

2. Infants and children

. [ The FFDCA Section 408 requires an additional tenfold margin of safety for the protection of infants and children in case of threshold effects to account for prenatal and postnatal toxicity, and an inadequate toxicity database. Where an adequate and reliable database is available and there is a lack of evidence for increased susceptibility, the FQPA safety factor may be reduced or removed.

An evaluation of susceptibility and uncertainty issues associated with SXS has been performed, and EPA has previously reduced the FQPA safety factor from the default 10X to 1X for the following reasons:

•

• Th e availability of a substantial and scientifically sound mammalian toxicology database that includes acute, repeat dose, reproduction, developmental, chronic and carcinogenicity toxicity data for Hydrotropes, including CAS # 1300

- 72

- 7;

• OECD testing indicat ing that there w as no evidence of developmental toxicity or malformations in the developing offspring;

• There is no evidence to suggest that SXS would have an adverse effect on the reproductive organs;

SXS does not belong to a class of chemicals known or suspected of having5

adverse effects on the estrogen receptor or endocrine system. SXS in association with the structurally similar compounds included in the OECD Hydrotropes Category have been evaluated in acute, re peated dose, developmental, and chronic toxicity studies capable of detecting effects on endocrine mediated events. ]

F. International Tolerances

[ There are no known international tolerances for SXS specified in this petition .]