**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460** 

**OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION**  January 9, 2015 **MEMORANDUM SUBJECT:**  PC Code: 7 1 1 393, 711394 ; Poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 -

oxos u lfopropyl) - ω - hydroxy , alkyl ethers, disodium salts ; Human Health Risk Assessment and Ecological Effects Assessment to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert In gred ients in Pesticide Formulations . **All PC Code:** 711 9 33, 711 9 34 **DP Barcode:** N/A **Decision No.: N/A**  **Regulatory Action:** Inert Tolerance Exemption; 40 CFR 180.9 2 0 **Petition No: IN**  **- 10671**  **All CAS Reg.**  **No :**  **68954 -**  **91 -**  **6 and 68815 -**  **56 -**  **5 Inert Tracking No:**  **N/A FROM:**  Lisa Austin , Ph.D., Toxicologist

Chemistry , Inert and Toxicology Assessment Branch (CIT AB) Registration Division (7505P) **THROUGH:** Kerry

L eifer, Team Leader Chemistry , Inert and Toxicology Assessment Branch (CIT AB) Registration Division (7505P) **TO:** PV Shah , Ph.D., Branch Chief

Chemistry , Inert and Toxicology Assessment Branch (CIT AB) Registration Division (7505P)2

**EXECUTIVE SUMMARY** EPA received a petition ( IN - 10671 ) from Exponent , on behalf of BASF, requesting an exemption from the requirement of a tolerance for the use of pol y(ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydrox y, alkyl ethers, disodium salts specifically , for CAS Reg . No s . 68954 - 91 - 6 and 68815 - 56 - 5 as inert ingredient s used as surfactants in pesticide products used for seed treatment not to exceed 0.125% weight/weight on all food, feed and oil crops under 40 CFR p art 180.9 2 0 . E PA published the notice of filing (NOF) for this petition in the Federal Register on September 5 , 201 4 (79 FR 530 09 ) . No substantial c omments were received in response to this notice . Poly (ox y - 1,2 - ethanedi yl ), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydrox y, alkyl ethers, disodium salts , CAS Reg. No. 68954 - 91 - 6 consists of a C 10 - C 12 linear alkyl alkoxy carbon chain and average pol yethox yl ation (POE) =5 and CAS Reg. No. 68815 - 56 - 5 consists of a C 10 - C 16 linear carbon chain and average poly ethox yl ation (POE) = 4. 5 . Data are not available for CAS Reg. No. 68954 - 91 - 6 . However, subchronic studies are available on CAS Reg. No. 68815 - 56 - 5 . Since CAS Reg. No. 68954 - 91 - 6 (linear alkyl chain length C 10 - C 12 ) is a component of CAS Reg. No. 68815 - 56 - 5 (linear carbon chain length C 10 - C 16 ) the available data w ere used to bridge data to CAS Reg. No. 68954 - 91 - 6 . T hese studies are sufficient to assess the subchronic toxicity of CAS Reg. No. 68954 - 91 - 6 as the only difference between the compounds is the range of carbon chain lengths and the tes ting of the broader carbon chain length of C 10 - C 16 in CAS Reg . No. 68815 - 56 - 5 would include an y effects that might be seen in tests of the narrower - linear carbon chain length of C 10 - C 12 (in CAS Reg. No. 68954 - 91 - 6). Reproduction and developmental toxicity studies were not available for review for either compound, however, based on analogy to well - known metabolic pathway s for other linear alkyl ethers, the major pathway in the primary metabolism of both compounds is expected to be oxidative - reductiv e ether cleavage. Therefore, the metabolism of poly (oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers,) disodium salts would result in the formation of the corresponding alkyl alcohol alkox yl ate such as C12AE6 (CAS Reg . No. 9002 - 92 - 0), a substance previousl y reviewed by the Agency . C12AE6 is similar to poly(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts in carbon chain length and average ethox yl ation. Therefore, C12AE6 reproduction and developmental toxicity were used as surrogate data for potential reproductive and developmental effects of pol y( oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts. The acute oral and dermal toxicity of poly (oxy - 1,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxos u lfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts is low (toxicity category I V) . The LD 50 i s > 5 00 0 mg/kg in the rat (oral) and rabbit (dermal) . They are irritating to the ey es and non - irritating to the skin in rabbits . They are not dermal sensitizer s . Acute inhalation toxicity studies were not available. Subchronic toxicity

studies were available in the rat and dog for CAS Reg No. 68815 - 56 - 5 was administered via the diet in both studies . Ina 9 0 day oral toxicity

study in rats , decreased body weight gain was observed at 4% ( equivalent to 2 000 mg/kg/day (LOAEL ) ) of CAS Reg No. CAS 68815 - 56 - 5 . The NOAEL was 1% ( equivalent to 5 00 mg/kg/day) . In a 90 day toxicity study in dogs , toxicity was not observed at 5 00 mg/kg/day (N OAEL) , the highest dose tested.3

A d evelopmental toxicity study via gavage was available in rabbits . C12AE6 (CAS Reg. No. 9002 - 92 - 0) , a postulated metabolite of poly (oxy - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts , caused ataxia and decreased body weight gain in maternal animals at 100 mg/kg/day . The maternal NOAELwas 50 mg/kg/day . No data were available on fetal effects; therefore, this study was considered unacceptable. In a two - generation reproduction study in rats , C12AE6 (CAS Reg. No. 9002 - 92 - 0) , a postulated metabolite of poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts , caused decreased bod y weight gain in parental animals at 0.05% ( equivalent to 250 mg/kg/day). The NOAEL was 0.1 % ( equivalent to 50 mg/kg/day). Offspring toxicity

was manifested as decreased weight gain in pups, increased emb ry o lethalit y and soft tissue anomalies at 0.5% ( equivalent to 250 mg/kg/day). The NOAELwas 0.1% ( equivalent to 50 mg/kg/day). Although, fetal qualitative susceptibility is observed in this study concern , is low because it occurs onl y in the presence of maternal toxicity . Chronic/carcinogenicity

studies with poly (ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts were not available. However, a DEREK structural alert anal ys is was conducted with poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 12 ) - alkyl ethers, disodium salt (CAS Reg No. 68954 - 91 - 6) and indicated no structural alerts for carcinogenicity or mutagenicity . Therefore, pol y(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts are not e xpected to be carcinogenic. Mutagenicity

studies were not available for pol y(o xy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts . However, an Ames test is available on CAS Reg. No. 68439 - 50 - 9, a surrogate alkyl alcohol alkoxylate. The test was negative. Neurotoxicity

and i mmunotoxicity

studies were not available for review. However, evidence of neurotoxicity

and immunotoxicity

was not observed in the submitted studies. Metabolism studies on poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts were not available for review. However, based on analogy

to known metabolic pathway s for linear alkyl ethers, the major pathway in the primary meta bolism is expected to be oxidative - reductive ether cleavage. Therefore, the primary metabolism of poly (ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts occurs via oxidative - reductive ether h ydroly sis r esulting in the formation of linear alkyl alcohols and poly ethylene gl yc ol metabolites. The alcohols would undergo oxidation by

alcohol dehydrogenase and aldehy de deh ydrogenase to generate a fatty acid metabolite that is degraded b y β - oxidation to CO 2 and H 2 O . The poly ethylene gl yc ol metabolites would be degraded via oxidation by alcohol dehydrogenase and aldehy de dehydrogenase to generate a dienoic pol yeth yl ene ether acid that may be conjugated and excreted. Also, the alcohol function may be sulfated by sulfotransferases and excreted.4

EPA has determined that reliable data show the safety of infants and children would be adequatel y protected if the 10x FQPA SF w as retained to account for an incomplete database . There was no hazard attributable to a single exposure seen in the toxicity database for poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts . Therefore, poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u l fopropyl) - ω hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts are not expected to pose an acute risk. Chronic dietary

risk assessments were conducted on poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y 1 - oxos u lfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts (CAS Reg. No. 38640 - 62 - 9) using the Dietary

Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM - FCIDTM, Version 3 . 16 . The chronic anal ys is was based on a two - generation reproduction toxicity

study in rats with a LOAEL of 250 mg/kg/day based on decreased bod y weight gain . The NOAEL was 5 0 mg/kg/day . The uncertainty factor of 100 (10x for intraspecies variability

and 10x for inter species extrapolation) was used for the chronic endpoints. The 10x FQPA SF was retained to account for an incomplete database. One hundred percent crop treated was assumed, default processing factors and tolerance - level residues for all foods and use limitations of not more than 0.125 % by weight in pesticide formulations. Conse rvative estimated drinking water concentrations of (100 ppb) w ere incorporated directl y into the dietary

assessment. The chronic dietary risk assessment shows that the chronic dietary risk estimates are not of concern (i.e., <100% cPAD). For the U.S. pop ulation, the exposure for food and water utilized 5.1 % of the cPAD. The chronic dietary risk estimate for the highest exposed population subgroup , non - nursing infants, is 16.2 % of the cPAD. RD has not identified any concerns fo r carcinogenicity relating to poly (oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts ; therefore, a cancer dietary exposure assessment was not performed. Occupational handler and post - application risks are not of concern for all scenarios. In a closed bottle biodegradability test on CAS Reg. No. 68815 - 56 - 5 biodegraded to 80.7% after 28 day s. Therefore, poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfoprop yl ) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts are expected to biodegrade. Also, CAS R eg. N o. 68954 - 91 - 6 was over 90% biodegraded in seven day s by a bacteria culture using the surface tension method. They

are also not expected to be acutel y toxic to aquatic organisms base d on a 96 hour acute toxicity

study in rainbow trout . Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low - Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf . Taking into consideration all available information on poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts, CAS Reg. Nos. 68954 - 91 - 6 and 68815 - 56 - 5 , EPA concludes that there is a reasonable certainty that no harm will result to the general population or to infants and children from aggregate exposure to poly (ox y 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium5

salts , CAS Reg. Nos. 68954 - 91 - 6 and 68815 - 56 - 5 . Therefore, the establishment of an exemption from tolerance under 40 CFR 180.9 2 0 for residues of poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts specifically, for CAS Reg. Nos. 68954 - 91 - 6 and 68815 - 56 - 5 when used as an inert ingr edient in seed treatment pesticide formulations at a concentration not to exceed 0.125% by weight in the end - use formulation can be considered safe under section 408 of the FFDCA. **1 .**  **BACKGROUND** On November 2 6 , 201 3 Exponent submitted a petition ( IN - 10671 ) on behalf of BASF , Inc. requesting an exemption from the requirement of a tolerance for the use of poly (ox y - 1,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxos u lfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts (PE G - AESDS) specifically , for CAS Reg. Nos. 68954 - 91 - 6 and 68815 - 56 - 5 as inert ingredients used as surfactants in pesticide products used for seed treatment not to exceed 0.125% weight/weight on all food, feed and oil crops under 40 CFR part 180.920. EPA published the Notice of Filing for this petition in the Federal Register on September 5, 2014 (7 9 FR 530 09 ). No substantial comments were received in response to this notice. This document provides an assessment of the risk to human health and th e environment for poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts (PEG - AESDS ) specificall y, for CAS Reg. Nos. 68954 - 91 - 6 and 68815 - 56 - 5 as inert ingredient s used as surfactants in pesticide products used for seed treatment at a concentration not to exceed 0.125% by weight on all food, feed and oil crops . **2 .**  **PHYSICAL AND CHEMICAL PROPERTIES** The phy sicochemical data (Table 1) for pol y(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxos u lf opropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts are based on the EPI Suite phy sicochemical estimations for C12 (laury l) alkyl ether chain length and POE = 5 which should be the major constituent of the mixture of CAS Reg. No. 68815 - 56 - 5 , as postulated by the registrant . **Table 1.**  **Physical and Chemical Properties of Poly(oxy**  **- 1,2**  **- ethanediyl), α**  **- (3**  **- carboxy**  **- 1**  **-**

**oxos u**  **lfopropyl) -**  **ω -**  **hydroxy, alkyl ethers, disodium salts Parameter**  **Value Source**  Structure As it appears in the Registrant’s petition Chemical Name Poly(oxy - 1,2 - ethanediyl), α - (3 - carboxy - 1 - oxos u lfopropyl) - ω - hydroxy, (C 10 - C 16 ) - alkyl ethers, disodium salts CAS # 68954 - 91 - 6 and 68815 - 56 - 5 EPISuite Estimates6 Molecular Weight 616.72 Common Names PEG - AE SDS Melting Point (°C) 349.84 Boiling Point (°C) 831.50 Vapor Pressure ( Pa at 2 5  C) 1.16 E - 18 Partition Coefficient (Kow) - 4.91 Water Solubility @ 25  C (mg/L) 1E6 Henry's La w Constant 3.98 x 10 - 23 (atm m 3 /m ol) **3 .**  **Hazard A**  **ssessment** Poly (ox y - 1,2 - ethanedi yl ), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, alkyl ethers, disodium salts , CAS Reg. No. 68954 - 91 - 6 consists of a C 10 - C 12 linear alkyl alkoxy carbon chain and average pol yethox yl ation (POE) =5 and CAS Reg. No. 68815 - 56 - 5 consists of a C 10 - C 16 linear carbon cha in and average poly ethox yl ation (POE) = 4.5. Data are not available for CAS Reg. No. 68954 - 91 - 6. However, subchronic studies are available on CAS Reg. No. 68815 - 56 - 5. Since CAS Reg. No. 68954 - 91 - 6 (linear alkyl chain length C 10 - C 12 ) is a component of CAS Reg. No. 68815 - 56 - 5 (linear carbon chain length C 10 - C 16 ) the available data were used to bridge data to CAS Reg. No. 68954 - 91 - 6. These studies are sufficient to assess the subchronic toxicity of CAS Reg. No. 68954 - 91 - 6 as the only difference between the compounds is the range of carbon chain lengths and the testing of the broader carbon chain length of C 10 - C 16 in CAS Reg. No. 68815 - 56 - 5 would include any effects that might be seen in tests of the narrower - linear carbon chain length of C 10 - C 12 (in CAS Reg. No. 68954 - 91 - 6). Reproduction and developmental toxicity studies were not available for review for either compound, however, based on analogy to well - known metabolic pathway s for other linear alkyl ethers, the major pathway in the primary metabolism of both compounds is expected to be oxidative - reductive ether cleavage. Therefore, the metabolism of poly (oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers,) disodium salts would result in the formation of the corresp onding alkyl alcohol alkox yl ate such as C12AE6 (CAS Reg. No. 9002 - 92 - 0), a substance previousl y reviewed by the Agency . C12AE6 is similar to poly(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts in car bon chain length and average ethox yl ation. Therefore, C12AE6 reproduction and developmental toxicity were used as surrogate data for potential reproductive and developmental effects of pol y( oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts. **Acute Toxicity Studies Table 2. Acute Toxicity Profile of**  **Poly(oxy -**  **1,2 -**  **ethanediyl), α -**  **(3 -**  **carboxy**   ** 1** **- oxos**  **u lfopropyl)**  **- ω**  **- hydroxy,**  **(C 10**  **- C**  **16 )**  **- alkyl ethers, disodium salts** 

**Study Type Results**  **Toxicity Category**  Acute Oral - rat LD50 > 5,000 mg/kg bw IV Acute Dermal - ra

bbi t LD50 > 5,000 mg/kg bw IV7

**Table 2. Acute Toxicity Profile of Poly(oxy**  **- 1,2**  **- ethanediyl), α**  **- (3**  **- carboxy**  **** **1 -**  **oxos u**  **lfopropyl) -**  **ω -**  **hydroxy, (C**  **10 -**  **C 16**  **) -**  **alkyl ethers, disodium salts**

**Study Type Results**  **Toxicity Category**  Ey e Irritation - rabbit Irritant IV Dermal Irritation - rabbit Not Irritant Dermal - species unknown Not a sensitizer **9 0**  **- day Oral Tox**  **i city**  **- Rat:**  In a 9 0 d ay

oral toxicity

study , random bred rats (20/sex/dose) were administered CAS Reg. No . 68815 - 56 - 5 via the diet at concentrations of 0% (vehicle control), 0.25, 1 or 4% ( equivalent to 125, 500 or 2000 mg/kg/day) . The body weight and food consumption were recorded weekl y. Hematology ana ly sis and urinaly sis were conducted at 6 and 13 weeks. Histopathological examination was performed on 10 rats/sex in the high dose and vehicle control groups. Organ weights were taken f

or 10 rats/sex/dose level. The effects in this study were limited to a significant decrease in body weight gain in males and females at 4% when compared with the vehicle control group. The LOAEL was 4% ( approximately equivalent 2000 mg/kg/day) based on d ecreased bod y weight gain. The NOAEL was 1% ( equivalent 500 mg/kg/day) ( MRID 49219302 ) . **90 -**  **day Oral Toxicity -**  **Dog :**  In a 90 d ay

oral toxicity

study , purebred young beagle dogs ( 4 /sex/dose) were administered CAS Reg. No. 68815 - 56 - 5 via the diet at concentrations of 0% (vehicle control), 0. 12 , 0.50 or 2 % (equivalent to 0, 3 0, 125, 500 mg/kg/day) . The dogs were observed daily for clinical effects and body weight was recorded weekly . Hematology parameters were evaluated pre - test and monthly thereafte r. Urinaly sis and clinical chemistry were performed pre - test and at study termination. Gross pathology was performed on all animals in all dose groups, and organ weights were recorded for all animals. Histopathological evaluation w as performed on all an imals in all dose groups. Slight but n on - significant body weight loss was reported in the 2 % dose group when compared to controls. No changes in food consumption or feed efficiency were reported in an y dose group. No adverse treatment - related effects on hematology , organ weight, gross pathology , or histopathology were reported. The NOAEL was 2 % ( equivalent to 500 mg/kg/day) , the highest dose tested ( MRID 49219301 ) . **Reproduction/ Developmental Toxicity Stud**  **ies Rats**  In a two - generation study , developmental toxicity of C 12 AE 6 (CAS Reg. No. 9002 - 92 - 0) in rats was evaluated. Groups of 25 Charles River rats of both sexes were fed C 12 AE 6 in the diet at dosage levels of 0, 0.05, 0.1 and 0.5%, equivalent to 0, 25, 50 and 250 mg/kg/d ay . General8

behavior, appearance and survival were not affected by treatment. At the 0.5% dose level, adults and pups gained less weight than the control rats. Inthe 0.5% dose group, there was a statistical increase in embry o lethality and soft tissue anomalies and at the 0.1% there was a statistical decrease in mean f

etal liver weight. Neither of these effects was considered to be treatment related b y the authors as they showed no dose response characteristics. Although not specificall y reported, it appeared that the NOAEL for maternal toxicity was 0.1% ( equivalent to 50 mg/kg/d ay) . The LOAEL was 0.5% ( equival ent to 250 mg/kg/day) based on decreased weight gain. The NOAEL for developmental and teratogenic toxicity was set at the 0.1% ( equivalent to 50 mg/kg/d ay) dose le vel . The LOAEL was 0.5% ( equivalent to 250 mg/kg/day) based on decreased weight gain in pup s, increased embry o lethality and soft tissue anomalies. No more detailed study

information was provided (Talmage, 1994 as cite in MRID 49297601) . **Rabbits** In a study with C 12 AE 6 (CAS Reg. No. 9002 - 92 - 0) , twent y - five female rabbits were orall y administered doses of 0, 50, 100 or 200 mg/kg/d ay of C 12 AE 6 from day 2 to day 16 of gestation (NOT GIVEN)(Talmage, 1994). Caesareans were performed on the 28th day of pregnancy . A definite increase in maternal toxicity , evidenced by ataxia and a slight de crease in bod y weight was observed at 100 and 200 mg/kg/d ay . No effects were observed for parameters such as corpora lutea, implantations, number of live f etuses and spontaneous abortions. Nine control rabbits and 31 treated rabbits died during the stud y . Survi ving rabbits at the 200 mg/kg/d dose level generally

showed slight losses of body weight. Inseven treated and two control rabbits earl y deliveries were recorded. The NOAEL for this study based on the maternal toxicity was therefore assumed to be greater than 50 mg/kg/day . The LOAEL was 100 mg/kg bw/day based on ataxia and decreased body weight. No more detailed study information was available ( Little, 1977; Shell Chemicals Ltd., 2002; Talmage, 1994 as cited in MRID 49297601) . This study was considered unacceptable since fetal effects were not reported. **Chronic/Carcinogenicity** Chronic/carcinogenicity

studies with poly (ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxos u lfopropyl) - ω - hydroxy , alkyl ethers, disodium salts are not availa ble . However, a DEREK structural alert anal ys is was conducted with CAS Reg No. 68815 - 56 - 5 and indicated no structural alerts for carcinogenicity or mutagenicity . Although, DEREK results indicated an equivocal structural alert for nephrotoxicity , kidney related toxicity

was not observed in subchronic studies in rats and dogs treated with poly ( oxy - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts. Therefore, based on the lack of structural alerts for carcinogenicity and the absence of nephrotoxicity in submitted studies, poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts are not expected to be carcinogenic. **Mutagenicity** Mutagenicity

studies were not available for pol y(o xy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts . However, an Ames test is9

available on CAS Reg. No. 68439 - 50 - 9, a surrogate alkyl alcohol alkoxylate. The test was negative (as cited in the registrant’s petition) . **Dermal Toxicity -**  **Rat** Neither dermal toxicity

nor dermal absorption studies are available for review for pol y(ox y 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts . **Neurotoxicity and Immunotoxicity** Neither neurotoxicity

nor immunotoxi city

studies are available for review. However, evidence of neurotoxicity or immunotoxicity was not observed in the submitted studies. **Metabolism -**  **Rat** Metabolism studies are not available for pol y(ox y - 1,2 - ethanediyl), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts . However, the registrant postulates that metabolism occurs as follows. This summary is reproduced from the registrant's petition. Based on analogy to known metabolic pathw ay s for linear alkyl ethers, such as dieth yl ethers, the major pathway in the primary

metabolism can be postulated to be oxidative - reductive ether cleavage .

• Oxidative - reductive ether h ydrol ys is occurring through the action of CYP 450 2E I or ether oxidase in the liver results in the formation of sulfosuccinic disodium sa lt aldehyde and al kyl poly ethox yl ate ether metabolites. • The sulfosuccinic disodium salt aldehyde metabolite should be readil y oxidized by aldeh yd e deh ydrogenase and gener ate su lfosuccinic acid and corresponding sodium salts which may

be excreted directly

and/or conjugated and excreted. ".... the PEG - AESDS the alkyl pol yethox yl ate ether metabolite is analogous to JI TF CST 1 Alkyl Alcohol Alkoxylate (AAA) non - ionic surfactants and the Alcohol Alkoxylate surfactants reported by

HERA (2007) and as such would undergo additional metabolism comparable to the AAA inert ingredients. "

• Consistent with proposed AAA surfactant metabolism (HERA, 2007), the PEG - AESDS alkyl pol yethoxylate ether metabolite may also undergo CYP 450 mediated - hydroly sis to generate Linear Alkyl Alcohols and Poly eth yl ene Gly col (Average POE = 5) metabolites. The C10 - C12 (or C10 - C16) Alcohol mixture would undergo sequential oxidation by alcohol dehydrogenase and aldehyde dehydrogenase to generate a fatt y acid metabolite that is sequentially

degraded by β - oxidation to C O 2 and H 2 O . • The Poly eth yl ene Gl yco l (POE average n= 5) metabolites would be oxidatively degraded by well - documented pathway s through sequentia l oxidation by alcohol dehydrogenase and aldeh yde deh ydrogenase ( Webste r et al., 2007 ) to generate a dienoic pol yethylene ether acid10

that may be conjugated and excreted. Alternatively , it is also report ed that the alcohol function may

be sulfated by

sulfo transferases and excreted. **Table 3**  **. Toxicology Profile for Poly(oxy**  **- 1,2**  **- ethanediyl), α**  **- (3**  **- carboxy**  **- 1**  **- oxos**  **u lfopropyl)**  **- ω**  **** **hydroxy, (C**  **10 -**  **C 16**  **) -**  **alkyl ethers, disodium salts Guideline No./ Study**  **Type Doses**  **Results** 9 0 Day Oral Toxicity Study - rat 0, 0.25, 1 or 4% ( equivalent to 125, 500 or 2000 mg/kg/day) NOAEL = 1% ( equivalent to 500 mg/kg/day) . LOAEL = 4% (2000 mg /kg/ day) based on decreased body weight gain. 90 Day Oral Toxicity Study - Dog 0 , 0.12, 0.50 or 2% ( equivalent to 30, 125, 500 mg/kg/day) NOAEL = 2% ( equivalent to 50 0 mg/kg/day) . LOAEL was not established. 2 - Generation Reproduction Study - Rats 0.05, 0.1 and 0.5% ( equivalent to equal to 25, 50 and 250 mg/kg/d ay) Maternal NOAEL = 0.1% ( equivalent to 50 mg/kg bw/day) . Maternal LOAEL = 0.5% ( equivalent to 250 mg/kg/day) based on decreased w eight gain. Offspring NOAEL = 0.1% ( equivalent to 50 mg/kg bw /day) . Offspring LOAEL = 0.5% ( equivalent to 250 mg/kg/day) based on decreased w eight gain in pups, increased embryo lethality and soft tissue anom alies. Devel o pm ental Toxicity Study - Rabbit 0, 50, 100 or 200 mg/kg bw /day Maternal NOAEL = 50 mg/kg bw /day . Maternal LOAEL = 10 0 mg/kg/day based on ataxia and decreased body weight. Developmental NOAEL =Not reported. Developmental LOAEL =Not reported. Ames Test Not Provided. Negative

**4 . Toxicity Endpoint Selection**  **Table 4. —**  **Summary of Toxicological Doses and Endpoints for Poly(oxy**  **- 1,2**  **- ethanediyl), α**  **- (3**  **- carboxy**  **- 1**  **- oxos**  **u lfopropyl)**  **- ω**  **- hydroxy,**  **(C 10**  **- C**  **16 )**  **- alkyl ethers, disodium salts**  **for Use in Human**  **Health Risk Assessment** Exposure/Scenario Point of Departure and Uncertaint y/ Safety Factors RfD, PAD, LOC for Risk Assessment Study and Toxicological Effects Ac ute dietary (General populations) An acute effect was not found in the database therefore an acute dietary assessment is not necessary. Chronic dietary NOAEL = 5 0 mg/kg/day Chronic RfD = 0.05 Two - Generation11

(All populations) UF A = 10x UF H = 10x FQPA SF = 1 0 x mg/kg/day cPAD = 0.05 mg/kg/day Reproduction Toxicity

Study - Rat LOAEL = 250 mg/kg/day based on decreased w eight gain. Derm al short - , intermediate - and long - term (1 to 30 days, 1 to 6 mo nths and >6 months) NOAEL = 5 0 mg/kg/day (Derm al absorption rate = 100%) UF A = 10x UF H = 10x FQPA SF = 1 0 x LOC for MOE = 1000 Two - Generation

Reproduction Toxicity Study - Rat LOAEL = 250 mg/kg/day based on decreased w eight gain. Inhalation short - , intermediate and long - term (1 to 30 days, 1 to 6 months and >6 months) NOAEL = 50 mg/kg/day ( I nhalation absorption rate = 100%) UF A = 10x UF H = 10x FQPA SF = 1 0 x LOC for MOE = 1000 Two - Generation

Reproduction Toxicity Study - Rat LOAEL = 250 mg/kg/day based on decreased w eight gain . Cancer (Oral, dermal, inhalation) Based on a DEREK structural alert analysis and the lack of mutagenicity , poly(oxy - 1,2 - ethanediyl), α - (3 - carboxy - 1 - oxos u lfopropyl) - ω - hydroxy, alkyl ethers, disodium salts are considered not likely to be carcinogenic. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF s = Extrapolation of subchronic to chronic exposure . FQPA SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic ). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. The two - generation reproduction study in the rat was selected for all exposure scenarios and durations for this risk assessment. The NOAE L in this study was 50 mg/kg/day . The LOAEL was 250 mg/kg/day

based on decreased weight gain . This study represents the lowest NOAEL in the database in the most sensitive species. The dermal and inhalation absorption rates were assumed 100%. The standard inter - and intra - species uncerta int y factors of 10x were applied. 5. **Special Considerations for Infants and Childre n**  Section 408 of the FFDCA provides that EPA shall apply an additional margin of safet y for infants and children in the case of threshold effects to account for prenatal and post natal toxicity and the completeness of the database on toxicity and exposure un less EPA determines that a different margin of safety will be safe for infants and children. EPA concludes that the FQPA safet y factor of 10x be retained for pol y(ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω hydrox y, (C 10 - C 16 ) - alkyl ethers, diso dium salts for the following reasons: i. The database is considered adequate for FQPA assessment. The following acceptable studies are available: 90 - Day stud ies in the rat and dog ( 2 ) Two generation study

in rat (1 , on structurally

similar chemical ) ii. The reproduction toxicity study with poly (oxy - 1,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxos u lfopropyl) - ω - hydroxy , alkyl ethers, disodium salts was not available for review .12

However, a two - generation reproduction toxicity study in rats w as available on a postul ated metabolite that is similar in carbon chain length and average poly ethoxylation. In this study , parental toxicity (decreased weight gain) and offspring toxicity (decreased weight gain in pups, increased embry o lethality and soft tissue anomalies) were observed at 250 mg/kg/day . Although, qualitative fetal susceptibility is observed , concern is low because fetal toxicity occurs only in the presence of maternal toxicity , there is a well established NOAEL and the cRfD (0.050 mg/kg/day) is based on this s tudy. Therefore, these effects will be protected. iii. Neurotoxicity

studies were not available for review. However, signs of potential neurotoxicity were not observed in an y of the submitted studies. EPA concl uded that neurotoxicity and developmenta l neurotoxicity studies are not required at this time. i v. Immunotoxicity

studies were not available for review. However, signs of potential immunotoxicity

were not observed in an y of the submitted studies. EPA concluded that the immunotoxicity

study is not required at this time. v. The dietary

food exposure assessment utilizes proposed tolerance level or higher residues and 100% CT information for all commodities. Inaddition, a conservative drinking water concentration value of 100 parts per billio n (ppb) was used to assess the contribution to drinking water. By using these screening - level assessments, chronic exposures/risks will not be underestimated. Taking into consideration the available information, EPA concludes the additional 10X FQPA safet y factor be retained to account for an incomplete database. **6 . Exposure**  **Assessment** 1. Inevaluating dietary

exposure to the poly (ox y - 1,2 - ethanedi yl ), α - (3 - c arboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts , EPA considered exposure under the petitioned for exemptions from the requirement of a tolerance. EPA assessed dietary exposures from poly (ox y - 1,2 - ethanediyl), α - (3 - carboxy- 1 - oxos u lfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts in food as follows: i. Acute exposure. No adverse effects attributable to a single exposure of poly (ox y - 1,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxos u lfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts were seen in the toxicity databases. Therefore, an acute dietary risk assessment for pol y(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxos u lfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts is not necessary . ii. Chronic exposure . In conducting the chronic dietary exposure assessment using the Dietary Exposure Evaluation Model DEEM

–FCID TM , Version 3.16 , EPA used food consumption information from the U.S. Department of Agriculture’s (USDA’s) 2003 - 2008 National Health and Nutrition Ex amination Survey, What We Eat in America (NHANES/WWEIA). As to residue levels in food, no residue data were submitted13 for poly (oxy - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts . Inthe absence of specific residue data, EPA has developed an approach which uses surrogate information to derive upper bound exposure estimates for the subject inert ingredient. Upper bound exposure estimates are based on the highest tolerance for a gi ven commodity from a list of high use insecticides, herbicides, and fungicides. A complete description of the general approach taken to assess inert ingredient risks in the absence of residue data is contained in the memorandum entitled ‘‘Alkyl Amines Pol yalkox yl ates (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts,’’ (D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID number EPA

–HQ

– OPP

–2008

– 0738. In the dietary

exposure assessment, the Agency assumed that the residue level of the inert ingredient would be no higher than the highest tolerance for a given commodity . Implicit in this assumption is that there would be similar rates of degradation (if any) between the active and inert ingredient and that the concentration of inert ingredient in the scenarios leading to these highest levels of tolerances would be no higher than the concentration of the active ingredient. The Agency

believes the assumptio ns used to estimate dietary exposures lead to an extremely conservative assessment of dietary risk due to a series of compounded conservatisms. First, assuming that the level of residue for an inert ingredient is equal to the level of residue for the activ e ingredient will overstate exposure. The concentrations of active ingredient in agricultural products are generall y at least 50 percent of the product and often can be much higher. Further, pesticide products rarel y have a single inert ingredient; rathe r there is generall y a combination of different inert ingredients used which additionally reduces the concentration of any single inert ingredient in the pesticide product in relation to that of the active ingredient. In the case of poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts , EPA used the aforementioned assumptions to conduct the dietary exposure assessment. Second, the conservatism of this methodology is compounded by

EPA’s decision to ass ume that, for each commodity , the active ingredient which will serve as a guide to the potential level of inert ingredient residues is the active ingredient with the highest tolerance level. This assumption overstates residue values because it would be highl y unlikel y, given the high number of inert ingredients, that a single inert ingredient or class of ingredients would be present at the level of the active ingredient in the highest tolerance for every commodity . Finall y, a third compounding conservatism is EPA’s assumption that all foods contain the inert ingredient at the highest tolerance level. In other words, EPA assumed 100 percent of all foods are treated with the inert ingredient at the rate and manner necessary to produce the highest residue leg all y possible for an active ingredient. In summary, EPA chose a very

conservative method for estimating what level of inert residue could be on food, then used this methodology to choose the highest possible residue that could be found on food and assumed that all food contained this residue. No14 consideration was given to potential degradation between harvest and consumption even though monitoring data shows that tolerance level residues are typically one to two orders of magnitude higher than actual resi dues in food when distributed in commerce. Accordingl y, although sufficient information to quantify actual residue levels in food is not available, the compounding of these conservative assumptions will lead to a significant exaggeration of actual exposur es. EPA does not believe that this approach underestimates exposure in the absence of residue data. iii. Cancer. Based on a lack of structural alerts in a DEREK structural alert analy sis and the lack of mutagenicity , poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts are not expected to be carcinogenic. Therefore , a cancer dietary exposure assessment was not performed . 2. Dietary exposure from drinking water. For the purpose of the sc reening level dietary risk assessment to support this request for an exemption from the requirement of a tolerance for poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts , a conservative drinking water concentration value of 100 parts per billion (ppb) based on screening level modeling was used to assess the contribution to drinking water for chronic dietary

risk assessments for poly (oxy - 1,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxo sulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts . These values were directly entered into the dietary exposure model. 3. From non - dietary

exposure . The term ‘‘residential exposure’’ is used in this document to refer to non - occupational, n on - dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). However, residential exposure is not expected for pol y(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxos u lfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts as the use i s for agricultural (seed treatment) purposes only . **7 .**  **Aggregate Risk and Determination of Safety**  EPA determines whether acute and chronic pesticide exposures are safe b y comparing aggregate exposure estimates to the acute population adjusted dose ( aPAD ) and chronic population adjusted dose ( cPAD ) . The aPAD and cPAD represent the highest safe exposure s, taking into account all appropriate safet y factors ( SFs ) . EPA calculates the aPAD and cPAD b y dividing the POD b y all applicable UFs. For linear cancer risks, EPA calculates the probability of additional cancer cases given the estimated aggregate exposure. Short - , intermediate - , and chronic - term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the POD to ensure that the MOE called for b y the product of all a pplicable UFs is not exceeded. 1. Acute risk . There was no hazard attributable to a single exposure seen in the toxicity database for pol y(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) -15

alkyl ethers, disodium salts . Therefore, pol y(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxos u lfopropyl) - ω - hydroxy , alkyl ethers, disodium salts is not expected to pose an acute risk. 2. Chronic risk . A chronic aggregate risk assessment takes into account exposure estimates from chronic dietary

consumption of food and drinking water using the exposure assumptions discussed in thi s unit for chronic exposure. Since there are no residential uses, chronic aggregate exposure takes into account food and water dietary exposure s onl y. Th e chronic dietary exposure from food and water to pol y(ox y - 1 ,2 - ethanedi yl ), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω hydrox y, alk yl ethers, disodium salts (CAS Reg. No s . 68954 - 91 - 6 and 68815 - 56 - 5) are 5.1 % of the cPAD for the U.S. population and 16.2 % of the cPAD for non - nursing infants , the most highl y exposed population subgroup. 3. Short - and Intermediate - term risks. Short - and intermediate - term aggregate exposure takes into account short - and intermediate - term residential exposure s plus chronic exposure to food and water (considered to be a background exposure level). Since, poly(ox y - 1,2 - ethanedi yl ), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts has no uses that would result in short - or intermed iate - term residential exposure s , the Agency has determined that it is appropriate to aggregate chronic exposure through food and water only . 4 **.** Aggregate cancer risk for U.S. population . The EPA has not identified any concerns for carcinogenicity

relat ing to poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts . **8 .**  **Occupational Exposure/Risk Pathway A.**  **Occupational Handler**  **Risk** The occupational exposure/risk from commercial seed treatment was determined using the HED (Health Effects Division) “Occupational Exposure and Risk From Commercial Seed Treatment - Margin of Exposure (MOE) Calculation”. For this current assessment , default v alues were used for the amount of seed/day that are t ypicall y treated at commercial seed treatment facilities on soy bean (Appendix) . The s oy bean crop was selected because it has the highest amount of seeds treated per day . T he occupational exposure assessment was based upon a toxicological No Observed Adverse Effect Level (NOAEL) of 50 mg/kg/day from a two generation reproduction toxicity study in rat s. Therefore, the Agency assumes 100 % absorption via the dermal and inhalation routes of exposure. The Agency

believes that ty

picall y commercial seed treatment pesticide handlers would be exposed to short - term (1 - 30 day s) exposures. However, in the event that intermediate - term exposures (1 - 6 months) might occur this exposure scenario was includ ed in the assessment. A Margin of Exposure (MOE)  than 100 0 is adequate to protect pesticide handlers and for post - application exposures to agricultural workers. Provided that occupational pesticide handlers16

use label prescribed PPE (i.e., long pants , long sleeved shirt, shoes + socks and chemical resistant gloves such as nitrile, butyl, neoprene, barrier laminate, pol yvin yl chloride or Viton), MOEs > 100 0 and are therefore not of concern. The MOEs presented are for short - (1 - 30 day s) and intermediate - term (1 - 6 months) exposures. RD traditionally

considers a level of concern (LOC) for risk assessments to be an MOE of 100 based on the standard 10X inter and 10X intra species extrapolation safety factors . An additional 10x FQPA safety f actor was applied to account for an incomplete data . Therefore, the LOC was for MOEs below 100 0 . **B. Occupational Post application Risk**  RD uses the term post - application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pes ts or harvesting. Post - application exposure levels vary over time and depend on such things as the ty pe of activity , the nature of the crop or target that was treated, the ty pe of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatl y reduce the potential for post - application exposure. P ost - application exposure is not expected based on poly (ox y - 1,2 - ethanedi yl), α - (3 - carbox y 1 - oxosulfopropyl) - ω - h ydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts’ use as a seed treatment. Therefore, post - application exposure was not assessed. **9 .**  **Cumulative Exposure**  **:** Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify , or revoke a tolerance, the EPA consider "available information" concerning the cumulative effects of a particular pesticide's residues and "other substances that have a common mechanism of toxicity ." Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity , EPA has not made a common mechanism of toxicity

finding as poly (oxy - 1,2 - ethanedi yl ), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts and any other substances and, this material does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that poly (oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxos u lfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts have a common mechanism of toxicity

with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released b y EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substanc es found to have a common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/. **10 .**  **Enviro n**  **mental Fate**17

In a Closed Bottle Read y Biodegradab ility Test (OECD 301D) an estimated 80.7% degradation of CAS Reg. No. 68815 - 56 - 5 occurred within 28 - Day s (Lee, 1993) . Also, u sing the surface tension method, it was found that CAS RN 68954 - 91 - 6 was over 90% biodegraded in seven day s by

a bacteria culture acclimated to the surfactant beforehand (MRID 49219305 ) . **11 .**  **Ecotoxic i**  **ty** A 96 hour acute toxicity

study was conducted on rainbow trout with concentrations of CAS Reg. No. 68954 - 91 - 6 at 0, 62.5, 125, 250, 500 and 1000 ppm. The L C50 = 218, demonstrating that CAS Reg. No. 68954 - 91 - 6 is not acutel y toxic to rainbow trout ( MRID 492 19307 ) . A 96 hour acute toxicity

study was also conducted with Bluegill Sunfish ( MRID 49219304 ) . The fish were treated with 0, 24, 32, 42, 56 and 75 mg/l of CAS Reg. No. 68954 - 91 - 6 . The L C50=67 mg/l. Therefore, based on these studies, poly (ox y - 1,2 - ethanediyl), α - (3 - carboxy- 1 - oxos u lfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts surfactants are not expected to be acutel y toxic to aquatic organisms. **1 2**  **. Enviro**  **n mental Justice**  Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Lo w - Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ). As a part of every

pesticide risk assessment, OPP considers a large variet y of consumer subgroups according to well - established procedures. In line with OPP policy , HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by

Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are anal yz ed and categorized by

subgroups based on age, season of the y ear, ethnic group, and region of the country . Additionally , OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non - dietary

exposures based on home use of pesticide products and associated ri sks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. Further considerations are currentl y in development as OPP has committed resources and expertise to the development of speci alized software and models that consider exposure to b ys tanders and farm workers as well as lifest yl e and traditional dietary patterns among specific subgroups. **1 3**  **. Human Studies** 18

This assessment relies in part on data from studies in which adult human s ubjects were intentionally

exposed to a pesticide. These studies, listed below, have received the appropriate ethical review for use in risk assessment. The PHED Task Force, 1998. The Pesticide Handler Exposure Database (PHED), Version 1.1. Task Force members: Health Canada, U.S. Environmental Protection Agency , the California Department of Pesticide R egulation, and the American Crop Protection Association; released August 1998. **1 4**  **. Risk Characterization** EPA received a petition ( IN - 10671 ) from Exponent, on behalf of BASF, requesting an exemption from the requirement of a tolerance for the use of pol y(ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, alkyl ethers, disodium salts specifically , for CAS Reg. Nos. 68954 - 91 - 6 and 6 8815 - 56 - 5 as inert ingredient s used as surfactants in pesticide products used for seed treatment not to exceed 0.125% weight/weight on all food, feed and oil crops under 40 CFR part 180.920 . E PA published the notice of filing (NOF) for this petition in th e Federal Register on September 5, 2014 (79 FR 530 09 ). No substantial comments were received in response to this notice. Poly (ox y - 1,2 - ethanedi yl ), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, alkyl ethers, disodium salts , CAS Reg. No. 68954 - 91 - 6 consists of a C 10 - C 12 linear alkyl alkoxy carbon chain and average pol yethox yl ation (POE) =5 and CAS Reg. No. 68815 - 56 - 5 consists of a C 10 - C 16 linear carbon chain and average poly ethox yl ation (POE) = 4.5. Data are not available for CAS Reg. No. 68954 - 91 - 6. However, subchronic studies are available on CAS Reg. No. 68815 - 56 - 5. Since CAS Reg. No. 68954 - 91 - 6 (linear alkyl chain length C 10 - C 12 ) is a component of CAS Reg. No. 68815 - 56 - 5 (linear carbon chain length C 10 - C 16 ) the available data were use d to bridge data to CAS Reg. No. 68954 - 91 - 6. These studies are sufficient to assess the subchronic toxicity of CAS Reg. No. 68954 - 91 - 6 as the only difference between the compounds is the range of carbon chain lengths and the testing of the broader carbon chain length of C 10 - C 16 in CAS Reg. No. 68815 - 56 - 5 would include any effects that might be seen in tests of the narrower - linear carbon chain length of C 10 - C 12 (in CAS Reg. No. 68954 - 91 - 6). Reproduction and developmental toxicity studies were not availab le for review for either compound, however, based on analogy to well - known metabolic pathway s for other linear alkyl ethers, the major pathway in the primary metabolism of both compounds is expected to be oxidative - reductive ether cleavage. Therefore, the metabolism of poly (oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers,) disodium salts would result in the formation of the corresponding alkyl alcohol alkox yl ate such as C12AE6 (CAS Reg. No. 9002 - 92 - 0), a substance pre viousl y reviewed by the Agency . C12AE6 is similar to poly(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts in carbon chain length and average ethox yl ation. Therefore, C12AE6 reproduction and developme ntal toxicity were used as surrogate data for potential reproductive and developmental effects of pol y( oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts.19

The acute oral and dermal toxicity of poly (oxy - 1 ,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts is low (toxicity category I V). The LD 50 i s >5000 mg/kg in the rat (oral) and rabbit (dermal). They are irritating to the ey es and non - irritating to the skin in rabbits. They are not dermal sensitizers. Acute inhalation toxicity studies were not available. Subchronic toxicity

studies were available in the rat and dog for CAS Reg No. 68815 - 56 - 5 was administered via the diet in both studies. In a 90 day ora l toxicity

study in rats, decreased body weight gain was observed at 4% ( equivalent to 2000 mg/kg/day (LOAEL )) of CAS Reg No. CAS 68815 - 56 - 5. The NOAEL was 1% ( equivalent to 500 mg/kg/day). In a 90 day toxicity study in dogs, toxicity

was not observed at 500 mg/kg/day (NOAEL), the highest dose tested. A developmental toxicity study via gavage was available in rabbits. C12AE6 (CAS Reg. No. 9002 - 92 - 0) , a postulated metabolite of poly (oxy - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts, caused ataxia and decreased body weight gain in maternal animals at 100 mg/kg/day . The maternal NOAELwas 50 mg/kg/day . No data were available on fetal effects; therefore, this study was considered unacceptable. In a two - generation reproduction study in rats, C12AE6 (CAS Reg. No. 9002 - 92 - 0) , a postulated metabolite of poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts, caused decreased body weight gain in parenta l animals at 0.05% (equivalent to 250 mg/kg/day). The NOAEL was 0.1% (equivalent to 50 mg/kg/day). Offspring toxicity

was manifested as decreased weight gain in pups, increased embry o lethalit y and soft tissue anomalies at 0.5% ( equivalent to 250 mg/kg/d ay). The NOAELwas 0.1% ( equivalent to 50 mg/kg/day). Although, fetal qualitative susceptibility is observed in this study concern, is low because it occurs onl y in the presence of maternal toxicity . Chronic/carcinogenicity

studies with poly (ox y - 1,2 - eth anedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts were not available. However, a DEREK structural alert anal ys is was conducted with poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 12 ) - alkyl ethers, disodium salt (CAS Reg No. 68954 - 91 - 6) and indicated no structural alerts for carcinogenicity or mutagenicity . Therefore, pol y(ox y - 1,2 - ethanedi yl ), α - (3 - carboxy - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts are not e xpected to be carcinogenic. Mutagenicity

studies were not available for pol y(o xy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts . However, an Ames test is available on CAS Reg. No. 68439 - 50 - 9, a surrogate alkyl alcohol alkoxylate. The test was negative. Neurotoxicity

and immunotoxicity

studies were not available for review. However, evidence of neurotoxicity

and immunotoxicity was not observed in the submitted studies. Metabolism studies on poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts were not available for review. However, based20

on analogy

to known metabolic pathway s for linear alkyl ethers, the major pathway in the primary metabolism is expected to be oxidative - reductive ether cleavage. Therefore, the primary metabolism of poly (ox y - 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethe rs, disodium salts occurs via oxidative - reductive ether h ydroly sis resulting in the formation of linear alkyl alcohols and poly ethylene gl yc ol metabolites. The alcohols would undergo oxidation by

alcohol dehydrogenase and aldehy de deh ydrogenase to generat e a fatty acid metabolite that is degraded b y β - oxidation to CO 2 and H 2 O . The poly ethylene gl yc ol metabolites would be degraded via oxidation by alcohol dehydrogenase and aldehy de dehydrogenase to generate a dienoic pol yeth yl ene ether acid that may be conjugated and excreted. Also, the alcohol function may be sulfated by

sulf otransferases and excreted. EPA has determined that reliable data show the safety of infants and children would be adequatel y protected if the 10x FQPA SF w as retained to account for an incomplete database. There was no hazard attributable to a single exposure seen in the toxicity database for poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts . Therefore, poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω hydrox y, (C 10 - C 16 ) - alkyl ethers , disodium salts are not expected to pose an acute risk. Chronic dietary

risk assessments were conducted on poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts (CAS Reg. No. 38640 - 62 - 9) using the Dietary

Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM - FCIDTM, Version 3. 16 . The chronic anal ys is was based on a two - generation reproduction toxicity

study in rats with a LOAEL of 250 mg/kg/day based on decreased body weight gain. The NOAEL was 50 mg/kg/day . The uncertainty factor of 100 (10x for intraspecies variability

and 10x for inter species extrapolation) was used for the chronic endpoints. The 10x FQPA SF was retained to account for an incomplete database. One hundred percent crop treated was assumed, default processing factors and tolerance - level residues for all foods and use limitations of not more than 0.125% by weight in pesticide formulations. Conservative estimated drinking water concentrations of (100 ppb ) w ere incorporated directl y into the dietary

assessment. The chronic dietary risk assessment shows that the chronic dietary risk estimates are not of concern (i.e., <100% cPAD). For the U.S. population, the exposure for food and water utilized 5.1% of the cPAD. The chronic dietary risk estimate for the highest exposed population subgroup, non - nursing infants, is 16.2 % of the cPAD. RD has not identified any concerns for carcinogenicity relating to poly (oxy- 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl ) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts ; therefore, a cancer dietary exposure assessment was not performed. Occupational handler and post - application risks are not of concern for all scenarios. In a closed bottle biodegradability test on CAS Reg. No. 68815 - 56 - 5 biodegraded to 80.7% after 28 day s. Therefore, poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y, (C 10 - C 16 ) - alkyl ethers, disodium salts are expected to biodegrade. Also, CAS R eg. N o. 68954 - 91 - 6 was over 90% biodegraded in seven day s by a bacteria culture using the surface tension method. They

are also not expected to be acutel y toxic to aquatic organisms based on a 96 hour acute toxicity

study in rainbow trout.21

Potential areas of environment al justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low - Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf . Taking into consideration all available information on poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 1 6 ) - alkyl ethers, disodium salts, CAS Reg. Nos. 68954 - 91 - 6 and 68815 - 56 - 5 , EPA concludes that there is a reasonable certainty that no harm will result to the general population or to infants and children from aggregate exposure to poly (ox y 1,2 - ethanedi yl ), α - (3 - carboxy- 1 - oxosulfopropyl) - ω - hydrox y , (C 10 - C 16 ) - alkyl ethers, disodium salts , CAS Reg. Nos. 68954 - 91 - 6 and 68815 - 56 - 5 . Therefore, the establishment of an exemption from tolerance under 40 CFR 180.920 for residues of poly (ox y - 1,2 - ethanediyl), α - (3 - carbox y - 1 - oxosulfopropyl) - ω - hydroxy , (C 10 - C 16 ) - alkyl ethers, disodium salts specifically , for CAS Reg. Nos. 68954 - 91 - 6 and 68815 - 56 - 5 when used as an inert ingredient in seed treatment pesticide formulations at a concentration not to exceed 0.125% by weight in the end - use formulation can be considered safe under section 408 of the FFDCA. **REFERENCES** BASF. (2014) References to Support the Petition for Exemption from the Requirement of a Tolerance for Residues of Poly Gl ycol Alkyl Ether Sulfosuccinate Disodium Salts (PEG AESDS) Surfactants as Inert Ingredients for Seed Treatment under 40 CFR 180.920. BASF - TP 001 - 14 - 01. MRID 49297601. Bowman, J.H. ( 1987 ) . Acute toxicity of Ct - 315 - 87 to bluegill sunfish (lepomis macrochirus).Unpublished report, Anal yt ic al Bio - Chemistry L aboratories, Inc, Columbia, Missouri, Report Number 36259. MRID 49219304. Cooke, D. ( 1990 ) . Aquatic toxicity tests versus onchorhy

ncus m ykiss. Unpublished report, United States Testing Company , Inc., Hoeboken, New Jersey , Study Number 06 3102 - 10 . MRID 49219307. Lee, C. (1993). Read y Bi odegradabilit y - Closed Bottle Test. Unpublished report, Exxon Biomedical Sciences Inc., East Millston, New Jersey , Study I D 143994. MRID 49219305. Tegeris, A.S. (1975) Ninety - day Dog Feeding Study

on A - 102. Unpublished report, Pharmacopathics Research Laboratories, Inc., Laurel, Maryland, Study I D 75 - 101 . MRID 4921930 1 . Underwood, P.C., Tegeris, A.S. (1975) Ninet y - day Rat Feeding Study

on A - 102. Unpublished report, Pharmacopathics Research Laboratories, In c., Laurel, Maryland, Study I D 90R - A102. MRID 49219302.22

**APPENDIX** EPA Ver. 3.16, 03 - 08 - d US EPA Ver. 3.16, 03 - 08 - d DEEM - FCID Chronic analysis for PEG - AESDS NHANES 2003 - 2008 2 - day Residue file name: C: \ Documents and Settings \ laustin \ My Documents \ DEEM Version 3.16 \ INERTS_57ACTIVE_100PPBH2OREV PEG registrant.R08 Adjustment factor #2 used. Analysis Date 09 - 11 - 2014 /12:08:01 Residue file dated: 09 - 11 - 2014/12:07:14 Reference dose (RfD, Chronic) = .05 mg/kg bw/day COMMENT 1: Inert 57 active ingredients + drinking water (100ppb)

============================================================================= == Total exposure by population subgroup

-----------------------------------------------------------------------------

-- Total Exposure

----------------- ------------------ Population mg/kg Percent of Subgroup body wt/day Rfd

-------------------------------------- ------------- ---------------- Total US Population 0.002562 5.1% Hispanic 0.002511 5.0% Non - Hisp - White 0.002613 5.2% Non - Hisp - Black 0.002163 4.3% Non - Hisp - Other 0.002966 5.9% Nursing Infants 0.002510 5.0% Non - Nursing Infants 0.008096 16.2% Female 13+ PREG 0.002380 4.8% Children 1 - 6 0.004042 8.1% Children 7 - 12 0.002310 4.6% Male 13 - 19 0.001770 3.5% Female 13 - 19/NP 0.001949 3.9% Male 20+ 0.002298 4.6% Female 20+/NP 0.002577 5.2% Seniors 55+ 0.002401 4.8% All Infants 0.006372 12.7% Female 13 - 50 0.002445 4.9% Children 1 - 2 0.004779 9.6% Children 3 - 5 0.003753 7.5% Children 6 - 12 0.002457 4.9% Youth 13 - 19 0.001860 3.7% Adults 20 - 49 0.002446 4.9% Adults 50 - 99 0.002440 4.9% Female 13 - 49 0.002442 4.9%23

-------------------- ------ --------------------------------------------------- **OCCUPATIONAL EXPOSURE AND RISK FROM COMMERCIAL SEED TREATMENT MARGIN OF EXPOSURE (MOE) CALCULATION**  **- Soybean** 

HANDLER EXPOSURES **Unit Exposure (UE) mg/lbs.ai**  **Daily Exposure**  **mg/kg/day Total Combined Short**  **- and**  **Intermediate -** **term MOE Dermal**  **Inhalation Dermal**  **Inhalation Dermal & Inhalation**  Loader / Applicator: 0.0230 0.00034 0.000716 0.000011 68798

Sewer: 0.0062 0.00023 0.000193 0.000007 249725 Bagger: 0.0091 0.00016 0.000283 0.000005 173405 Mu ltiple Activities: 0.0420 0.00160 0.001308 0.000050 36829