Page 2 of 7

1.0 Executive Summary

HED has prepared a qu alitative human health risk assessment to support registration review for

the uses of dioctyl sodium sulfosuccinate (DSS) as an active ingredient and as an inert ingredient in pesticides. HED primarily considered the HED scoping document , and its supporti ng documents, in support of registration review (LaMay, 12/1 0 /1 0

, D 379581 )

. Based on the low toxicity of DSS

, the chemical’s classification by the U.S. FDA as Generally Recognized as Safe (GRAS) as a food additive (21 CFR 178.3400)

, and its use as a pharmaceutical drug administered in much higher doses than would result from any potential pesticide exposures, HED has determined that a quantitative human health risk assessment is not required under registration review for the existing uses of DSS

.

Dio ctyl sodium sulfosuccinate (DSS) is used as both an active ingredient and as an inert ingredient. As an active ingredient, there are no food uses. DSS is listed as the active i ngredient (insecticide) in pet shampoos and pet spray products, which are regi stered in combination with undecylenic acid (PC 085501)

.

DSS as an inert ingredient is used in multiple end

- use pesticide products for agricult ural and

non

- agricultural areas; in disinfectants and sanitizers used in residential and commercial settings;

and as a wetting agent in industrial, dr ug, cosmetic, and food products. As an inert ingredient

there are exemptions from the requirement of a tolerance established for DSS under 40 CFR

180.910 and 180. 930. T hese exemptions allow DSS as an inert ingredient to be used in pesticide formulations for pre

- and post

- harvest application to crops and as direct application to livestock.

Toxicity information for DSS is largely from literature studies; guideline toxi city studies are not available, and have been previously waived (except acute studies , which have been submitted ) by the Office of Pesticide Programs (OPP) because of its low toxicity. Dioctyl sodium sulfosuccinate has low acute oral, dermal and inhalatio n toxicity. It is neither a skin sensitizer nor a skin or eye irritant. Toxicity to offspring occurred in the reproduction and developmental studies only at high doses. The subchronic toxicity, chronic toxicity, and mutagenicity studies

did not demonstr ate any significant toxicity of DSS.

No data deficiencies were identified for toxicology, residue chemistry or occupat ional and residential exposure. There are no dietary, residential, aggregate or occupational risks of concern

for DSS.

2.0 Regulatory Recommendations

Sufficient data are available to support HED’s decision to waive generic mammalian toxicity data requirements for d ioctyl sodium sulfosuccinate

. There are no outstanding data requirements.

Tolerances for residues of DSS in food are not required. There are exemptions from the requirement of a tolerance currently established for DSS under 40 CFR 180.910 and 180. 930

.

HED has no objection to continuing registration of the current DSS pestici de products.Page 3 of 7

3.0 Introduction

Dioctyl sodium sulfosuccinate is an active ingredient (insecticide) used in pet shampoos and pet spray products which are registered in combination with u ndecylenic acid (PC 085501 ). The currently registered products are formulated as a n emulsifiable concentrate (45729

- 2) and as a ready

- to

- use liquid (45729

- 4) and may be used on cats, dogs, and reptiles. The structure, chemical names, and other identifiers are found in the chemical identity table below.

Table 3.1. Che mical Identity

Common Name Dioctyl sodium sulfosuccinate

Chemical Name sodium 1,4

- bis(2

- ethylhexoxy)

- 1,4

- dioxobutane

- 2

- sulfonate

PC Code 079027

Chemical Abstracts No. 577

- 11

- 7 Registration Review

Case No. 4029

Chemical Class e.g. organophosphate, dinitroaniline, etc.

Chemical Structure

4.0 Hazard Identification and Dose

- Response Assessment

The hazard information in this document came principally from reports assessing DSS (PC code 079027) as an active ingredient (Steve Johnson, 8/4/95) and as an inert ingredient (Laura Bailey, 9/28/04). For the assessment of DSS as an active ingredient, all toxicity study data requirements, except for acute toxicity, were waived. The requirements were waived because of the extensive data available in the open li terature for this chemical showing very low toxicity, and also because of the approval by the Food and Drug Administration (FDA) in over

- the

- counter human drug products such as stool softeners and laxatives at much higher doses of DSS than would be

associa ted with pesticide

- related uses.

The review of DSS as an inert ingredient relied upon toxicity studies assessed by the International Programme on Chemical Safety/World Health Organization (IPCS/WHO), the Food and Agriculture Organization of the United Nat ions (FAO), a report submitted by the Synthetic Organic Chemical Manufacturers Association (SOCMA) Sulfossucinates Group under the High Production Volume (HPV) Challenge Program, and information from the Hazardous Substances Databank (HSDB).

Results of acute toxicity studies submitted by the registrant for DSS found that DSS was of low acute toxicity: toxicity category IV for acute oral testing and category III for acute dermal and inhalation testing. DSS was in toxicity category III for eye irritation and category IV for dermal

irritation. DSS was not a dermal sensitizer.Page 4 of 7

Studies reported and assessed by WHO, FAO, SOCMA, and from the HSDB included subchronic toxicity, chronic toxicity, mutagenicity, developmental effect, and reproduction

studies. S ubchronic oral toxicity studies in rats, rabbits, monkeys, dogs, and guinea pigs reported decreased weight gain, which may have been due to decreased palatability, because administration of DSS was associated with decreased food consumption. No pathologic al changes were noted in a 2

- year feeding study in rats. Two mutagenicity studies, an Ames assay and a chromosomal aberrations assay in CHO cells were negative.

DSS was tested in two 3

- generation reproductive studies. There was decreased pup survival at 250 and 500 mg/kg/day in one study. Doses in the second reproduction study were 0, 50, 250, or 500 mg/kg/day. The only effects observed were reduced parental and pup body weights, but there was no effect on survival or reproductive parameters in this study. Developmental toxicity testing in rats found increased fetal resorptions, exencephaly, microphthalmia, and spina bifida at 1,000 mg/kg/day with a NOAEL of 500 mg /kg/day.

Although toxicity to offspring occurred in the reproduction and developmen tal studies, there are few concerns for exposure because 1) the effects occurred at high doses and 2) DSS is an over

the

- counter drug administered in high doses to humans (500 mg for adults and 40 mg for children < 3 years of age), and was cleared by FDA f or these uses. According to the previous 2006 EPA assessment, the only warning in the Physician's Desk Reference for pregnant women taking DSS as a drug is to notify their doctor before taking the drug.

Because of the extensive literature data availabl e for DSS, its low toxicity, FDA’s approval of the chemical as a drug for use at much higher doses than would be experienced as a result of pesticide

- related uses, and the chemical’s classification by FDA as Generally Recognized as Safe (GRAS) as a food ad ditive (21 CFR 178.3400), HED concludes that additional toxicity data are not required, and that a quantitative risk assessment for pesticide

- related uses is not required.

Since this chemical was registered, there are now OPP guideline study requirements for neurotoxicity and immunotoxicity, however, these studies can be waived for the same reasons that the original guideline s tudies were waived, namely the long history of this chemical as a human drug and because significant toxicity is not expected. Endpoints were not selected for this chemical because the toxicity studies were waived. There are no reports of increased sensitivity to children from use of this product, nor is there any reason to anticipate sensitivity to children, ther efore the FQPA safety factor can be reduced to 1X.

5.0 Dietary Exposure and Risk Assessment

As an active ingredient, there are no food uses for DSS. However, exemptions from the requirement of a tolerance are established for DSS (as sodium dioctylsulfosuc cinate) under 40 CFR 180.910 and 180.930 which allow uses as inert ingredients in formulations intended for pre

and post

- harvest application to raw agricultural commodities and permits direct use on livestock. No residue chemistry data were submitted or are required to support the non

- food uses of DSS as an active ingredient. Further, no residue chemistry data were submitted to support the established inert ingredient uses, and based on the low toxicity of DSS, residue chemistry data are not required to support the established inert uses in both conventional and antimicrobialPage 5 of 7

pesticide formulations. Further, also based on the low toxicity of DSS, a quantitative dietary risk assessment is not required. HED concludes that there are no dietary risks of co ncern associated

with the established uses of DSS.

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

There are residential (non

- occupational) uses for the active ingredient DSS in pet shampoo and spray. The inert ingredient DSS can also be used in pesticide products used in non

- agricultural areas and it can be used as an inert ingredient in disinfectants and sanitizers for household uses. Residential exposure was not previously quantitatively assessed for either active or inert uses in pesticide products. Because of the low toxicity of DSS , quantitative residential handler and postapplication exposure assessments are not required. HED concludes there are no residential exposure risks of conc ern.

7.0 Aggregate Exposure/Risk Characterization

An aggregate assessment considers exposures from food, residential uses, and drinking water. As quantitative dietary and residential exposure assessments are not required for DSS acid, a quantitativ e aggregate assessment is not required either. Based on the low hazard associated

with DSS , HED concludes that aggregate risks are not of concern.

8.0 Cumulative Exposure/Risk Characterization

The Agency has not determined that DSS shares a common mec hanism of toxicity with other

chemical substances ; therefore, at this time, a cumulative risk assessment to support registration review is not required.

9.0 Occupational Exposure/Risk Characterization

There is potential for occupational ( handler and postapplication ) exposure to DSS as a pet product. Because of the low toxicity of DSS , a quantitative occupational exposure assessment is not required for these pet product uses . HED concludes there are no occupational exposure risks

of concern.

10.0 Public Health and Pesticide Epidemiology Data

A summary report listing incidents for DSS is available ( D380163

, K. Oo ). No incidents were reported to either OPP Incident Data System (IDS) or t he Centers for Disease Control and

Prevention/National In stitute for Occupational Safety and Health (CDC/NIOSH) S entinel Event Notification System for Occupational Risk (SENSOR) database for DSS. Because there are no incident cases reported for DSS , there does not appear to be a concern at this time that would warrant further investigation.Page 6 of 7

11.0 Tolerance Assessment and International Harmonization

There are no tolerances established for DSS; therefore, there are no issues with respect to

international ha rmonization associated with this registration review action.

12.0 Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the human health risk assessment, in accordance with U.S. Executive Orde r 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," http://www.eh.doe.gov/nepa/tools/guidance/Volume1/2

- 6

- EO_12898envjustice.pdf ). The Office of Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use of a pesticide when conducting human health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets within the U.S., and people who may be exposed when harvesting crops. Should these highest exposures indicate potential risks of concern, OPP further refines the risk assessments to ens ure that the risk estimates are based on the best available information.

13.0 Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, an d general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine in fluence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tes ts and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. EPA has reviewed the available data and endpoints were not selected for this chemical because significant toxicity is not expected and the tox icity studies were waived. However, as required by FFDCA section 408(p), dioctyl sodium sulfosuccinate is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a

chemical substance to interact with the estr ogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA

will determine which , if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and

establish a dose

- response relationship between the dose and the E, A, or T ef fect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. BetweenPage 7 of 7

October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 iner t ingredients. Dioctyl

sodium sulfosuccinate is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue

future EDSP orders/data call

- ins, requir ing the submission of EDSP screening assays for dioctyl

sodium sulfosuccinate

. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, pl ease visit our website: http://www.epa.gov/endo/

.

14.0 Human Studies

No human studies have been relied on for d ioctyl sodium sulfosuccinate risk assessments.

15.0 Data Requirements

None.

16.0 References

Author Barcode D ate Title J. Hayes NA 7/13/1995 EPA Reg. No./File Symbol 45729

- E

S. Johnson NA 8/4/1995 New Chemicals: Consideration of Unconditional Registration for the New Chemicals Dioctyl sodium sulfosuccinate and Undecylenic acid for use on dogs and cats to control fleas.

L. Bailey NA 9/28/2004 Butanedioic acid, sulfo

- , 1,4

- bis (2

- ethylhexyl) ester, sodium salt: Tolerance Reassessment Decision Document PC Codes 079027;

790130.

P. Wagner NA 6/30/2006 Inert Reassessments: Two Exemption from the Requirement of a Tolerance for Sodium Dioctyl Sulfosuccinate (CAS Reg. No. 577

- 11

- 7)

M. Kaul NA 6/2/2010 BEAD Chemical Profile for Registration Review: Dioctyl Sodium

Sulfosuccinate

K. Oo D380163 8/24/2010 Updated Review of Dioctyl Sodium Sulfosuccinate Incident Reports

A.LaMay 379581 12/16/10 Dioctyl Sodium Sulfosuccinate. Human Health Assessment Scoping Document in Support of Registration Review.