2

Table of Contents EXECUTIVE SUMMARY ................................ ................................ ................................ 3 I. BACKGROUND ................................ ................................ ................................ ................ 7 II. INERT INGREDIENT PROFILE ................................ ................................ ...................... 7 A. Summary of Uses ................................ ................................ ................................ .... 7 B. Physical Chemical Properties ................................ ................................ ................. 8 III. HUMAN HEALTH ASSESSMENT ................................ ................................ ................ 10 A. Summary of Data ................................ ................................ ................................ .. 10 B. Toxicity Endpoint Selection ................................ ................................ ................. 30 C. Special Considerations for Infants and Children ................................ .................. 31 IV. EXPOSURE ASSESSMENT ................................ ................................ ........................... 33 A. Dietary Exposure: ................................ ................................ ................................ . 33 i. Acute exposure ................................ ................................ ................................ ... 33 ii. Chronic exposure ................................ ................................ ............................... 33 iii. Can cer exposure ................................ ................................ ............................... 35 B. Dietary Exposure from Drinking Water: ................................ .............................. 35 C. Residential (Non - Occupational) Exposure: ................................ .......................... 35 i. From non - dietary exposure. ................................ ................................ ................ 36 V. AGGREGATE RISK ASSESSMENT ................................ ................................ ............. 37

i. Acute Dietary Risk. ................................ ................................ ............................. 37 ii. Chronic Dietary Risk. ................................ ................................ ........................ 37 iii. Aggregate Cancer Risk for U.S. Population. ................................ .................... 37 iv. Short - term Aggregate Risk. ................................ ................................ .............. 38 v. Intermediate - Term Aggregate Risk. ................................ ................................ .. 38 VI. OCCUPATIONAL EXPOSURE/RISK PATHWAY ................................ ....................... 39 VII. CUMULATIVE EXPOSURE ................................ ................................ .......................... 39 VIII . ENVIRONMENTAL JUSTICE STATEMENT ................................ ............................... 39 IX. ENVIRONMENTAL FATE CONSIDERATIONS ................................ ......................... 40 X. ECOTOXICITY ................................ ................................ ................................ ................ 41 XI. RISK CHARACTERIZATION ................................ ................................ ........................ 41 RE FERENCES ................................ ................................ ................................ ............................. 45 APPENDIX ................................ ................................ ................................ ................................ ... 493

EXECUTIVE SUMMARY In March 2014, Exponent (1150 Connecticut Ave., NW Washington, DC 20036) on behalf of ISK Biosciences (7470 Auburn Road, Suite A, Concord, OH 44077) submitted a petition to the EPA to amend 40 CFR 180.920 by establishing an exemption fro m the requirement of a tolerance for residues of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - (CAS Reg. No. 70280 - 68 - 1) when used as a n inert ingredient (antifoaming agent) in pesticide formulations applied to g rowing crops under 40 CFR 180.920 with a limitation of 10% by weight in the pesticide formulation. There is currently limited data available for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , however data are av ailable for a suitable cluster of structurally - related linear short chain sil oxane compounds. The cluster analysis and resultant bridging/read - across analysis include an evaluation of the available studies and modeled data to address the physicochemical pr operties , mammalian metabolism, mammalian toxic ity and environmental fate, of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - . 1,2 - P ropanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , was non - toxic via acute oral and acute dermal exposures and was negative for mutagenicity in the Ames assay. Based on the weight of evidence from the bridging/read - acro ss analysis of the linear short chain siloxane cluster, 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - i s expected to be non - toxic via acute inhalation exposure, non - irritating to the eyes and skin, and not result in skin sensitization. Oral repeated dose toxicity studies are available for the cluster of structurally similar linear short chain siloxane compounds , for durations ranging from 28 days up to one year in rats, rabbits and dogs. The lowest NOAELs were in the 25 mg/kg/day range for two 28 - day oral repeat dose rat studies and a 90 - day dog study. LOAEL s for these studies were primarily based on adverse liver effects . Dermal repeated dose toxicity studies are available for two of the structurally similar clu ster compounds. A 28 - day rat and 28 - day rabbit dermal toxicity study showed no adverse effects up to a limit dose of 1000 mg/kg/day. The NOAEL was 1000 mg/kg/day for both studies. Inhalation repe ated dose toxicity studies are available for three of the st ructurally similar cluster compounds. Both a 28 - day and 90 - day rat inhalation stud y are available as well as a 1 - year chronic inhalation study in rats . The lowest inhalation NOAE C was 3.9 mg/L (equivalent to 1000 mg/kg/day) in a 90 - day study which is at li mit dose. There is no evidence of increased reproductive or developmental toxicity based on quantitative or qualitative susceptibility of rat fetuses to the effects of cluster members following in utero exposure to the linear short chain siloxane compounds included in this analysis. In an oral combined repeated dose and reproductive and developmental screening study with the NOAEL for parental toxicity was 50 mg/kg/day and the developmental toxicity was 800 mg/kg/day (the highest dose tested) indicating no evidence of increased susceptibility. Because4

the oral route of exposure is most applicable to the dietary risk assessment, this study is the most relevant to the assessment of risk resulting from dieta ry exposure to 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - . Carcinogenicity data is available on the cluster of compounds and a DEREK (structure activity modeling) analysis was performed on 1,2 - propanediol,3 - [ 3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - to identify structural alerts for possible carcinogenicity . 1 ,2 - Propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is not expected to be carcinogenic based on a 1 - year chronic inhalation study on Fisher 344 rats with a similar cluster compound. An increase incidence of Leydig cell tumors (LCTs) in males was observed at all doses. However, due to the high background incidence of LCTs in Fischer 344 rats, this effect has been determined to not be treatment related. Renal tubular adenomas and carcinomas were also observed in the study but are attributable to ma l e rat specific alpha - 2μ - globulin mediated nephrotoxicity and therefore not relevant to cancer ri sk concerns in humans. Based on g enotoxicity studies on 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and structurally - related compounds that are all negative for genotoxic effects, a DEREK (structure - activity modeling) analysis in which no structural alerts for possible carcinogenicity were identified, and the lack of carcinogenicity in the available study, 1 ,2 - p ropanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl) oxy] - 1 - disiloxanyl]propoxy] - is not expected to be of concern for carcinogenicity. No immunotoxicity studies were available in the database for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - . However, evidence of immunotoxicity was not observed in the avai lable studies. No neurotoxicity studies were available in the database for 1,2 - propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - . However, evidence of neurotoxicity was not observed in the available studies. There are currently no publically - available metabolism studies for 1,2 - propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , however, relevant expected metabolic pathways can be determined based on metabolism for structural ly similar compounds and results obtained from the OECD Tool Box Analysis . The expected mammalian metabolic pathways involved in the degradation of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is a combination o f ether hydrolysis followed by ß oxidation of the carbon chain followed by methyl oxidation of the silyl methyl groups. Methyl oxidation would result in the formation of a mixture of primary and alcohol metabolites. The more polar primary alcohol functiona lities can both be conjugated and excreted directly or further oxidized to form a mixture of more polar carboxylic acid metabolites that could be readily conjugated and excreted. An acute dietary risk assessment was not conducted because no endpoint of co ncern following a single exposure was identified in the available studies. A chronic dietary exposure assessment was completed and performed using the Dietary Exposure Evaluation Model DEEM FCID TM , Version 3.16. The chron ic Reference Dose (cRfD) of 0.08 m g/kg/day was determined5

on the basis of the 28 - day oral toxicity studies in rats in which the NOAEL was 25 mg/kg/day and t he LOAEL was 250 mg/kg/day based on protoporp hyrin accumulation in the liver . This study provided the lowest NOAEL in the database (most sensitive endpoint) and will also provide the most protective limits for potential adverse human health effects. An UF of 100X (10 - fold for interspecies extrapolation and 10 - fold for intra speci es variability) and an FQPA safety factor of 3X (for subchronic to chronic study extrapolation) was applied to the NOAEL to derive the cRfD. Therefore, the chronic populati on - adjusted dose (cPAD) is 0.08 mg/kg/day. Based on analyses of estimated dietary risks for the general U.S. population and various population subgroups, the chronic dietary exposure estimates resulting from the use of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - as an inert ingredient in pe sticide formulations applied to growing crops at a maximum concentration of 5% in the pesticide formulation are below the Agency’s level of concern. The chronic dietary exposure estimate for the highest exposed population subgroup , children 1 - 2 years old is 88.3 % of the cPAD and 23.7 % of the cPAD for the general population. The Agency has not identified any concerns for carcinogenicity relating to 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - ; therefore, a cancer dietary exposure assessment was not performed and an aggregate cancer risk is not of concern. Short - term aggregate exposure takes into account short - term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - may be used as an inert ingredient in pesticide products that could result in short - term residential exposure. However t he Agency has determined that it is only appropriate to aggregate chronic exposure through food and water with short - term residential exposures for children because there are no endpoints of concern for residential dermal or inhalation toxicity that would affect adults . EPA has concluded the combined short - term aggregated food, water, and residential exposures results in an aggregate MOE of 334 for children. As the level of concern i s for MOEs that are lower than 3 00, these MOEs are not of concern. Intermediate - term aggregate exposure takes into account intermediate - term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - may be used as an inert i ngredient in pesticide products that could result in intermediate - term residential exposure. However t he Agency has determined that it is only appropriate to aggregate chronic exposure t hrough food and water with intermediate - term residential exposures for children because there are no endpoints of concern for residential dermal or inhalation toxicity that would affect adults . EPA has concluded the combined intermediate - term aggregated food, water, and residential exposures results in an aggregate MOE of 34 2 for children. As the level of concern i s for MOEs that are lower than 3 00, these MOEs are not of concern. Since there is no endpoint of concern selected for dermal or inhalation routes of exposure, a qualitative occupation al exposure assessment was n ot completed for the proposed use of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - as a pesticide inert ingredient and occupational exposure is not of concern.6

1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trime thylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is not volatile and has a moderately high Log Kow of 5.71 and low to negligible water solubility (0.03245 mg/L). 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is not expecte d to be volatil ized from bodies of water based on a Henrys Law C onstant of 2.03 x - 8 atm - m 3 /mole . Atmospheric oxidation is expected to be 3.676 hours half - life with indicates moderate capability to be broken down in air. Based on the Log Koc of 1.976, 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - will have low sorption to soil and sediment which may result in migration into ground water. The BCF of 2701 L/Lg wet - wt or Log BCF of 3.432 indicates a moderate potential to bioaccumulate. Biodegradation is expected to occur rapidly. Ecotoxicity estimations for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - were obtained utilizing EPA ECOSAR 1.1 model. The SAR based on Neutral Organics provided very conservative estimation of aquatic toxicity. Other than the earthworm estimations, the EPA model ECOSAR has indicated that the proposed inert ingredient may potentially be toxic to aquatic organisms. The ECOSAR modeled results for 1 ,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - are consistent with the trends and analysis for the siloxane cluster data that is reported from publically available sources and ECOSAR 1.1. Potential areas of enviro nmental 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," ht tp://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. Taking into consideration all available information on 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , EPA concludes that there is a reasonable certainty that no harm to any population subgroup will result from aggregate exposure to 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - when considering residential, , di etary exposure and all other nonoccupational sources of pesticide exposure for which there is reliable information. Therefore, the establishment of an exemption from the requirement of a tolerance under 40 CFR 180.920 for residues of 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - (CAS Reg. No. 70280 - 68 - 1 ) when used as a pesticide inert ingredient (antifroaming agent) in pesticide formulations applied to growing crops with a limitation of 5 % by weight in formulatio n, can be considered assessed as safe under section 408(q) of the FFDCA.7

I. BACKGROUND Exponent (1150 Connecticut Ave., NW Washington, DC 20036) on behalf of ISK Biosciences (7470 Auburn Road, Suite A, Concord, OH 44077 ) is requesting that EPA establish a t olerance exemption for 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - ( CAS Reg. No. 70280 - 68 - 1 ) as a pesticide inert ingredient (antifoaming agent) under 40 CFR 180.920 ( appli cation to growing crops only ) with a limitation of 5 % in formulation . The current toxicological and environmental data available for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is sufficient to support the proposed use as a food use pesticide in ert ingredient under 40 CFR 180.920 pre - harvest applications in accordance with the FQPA mandated risk assessment standard of “reasonable certainty of no harm.” This petition includes a review of the existing data available for 1,2 - propanediol,3 - [3 - [1,3,3, 3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , a Si - 3 siloxane, and the identification of a suitable cluster of structurally related linear short chain siloxane (Si - 2 to Si - 5) compounds. The cluster analysis and resultant bridging/read - acr oss analysis include an evaluation of the available studies and modeled data to address the physicochemical, mammalian metabolism, mammalian toxicological, environmental fate, and ecotoxicological endpoints. The issue of similarity of the cluster of compou nds and whether the data could be bridged was brought to members of the Office of Pollution Prevention and Toxics (OPPT), Structur e Activity Team (SAT). They determined that the information from the cluster provided in the submission to be relevant to the proposed inert ingredient . The cluster chemical identities are provided in Table 1. The physicochemical properties for the proposed cluster of the linear short chain siloxanes (Si - 2 to Si - 5) are homogenous and followed expected trends based on their struct ural similarity and increasing silicon chain length. Table 1. Linear Short Chain (Si - 2 to Si - 5) Siloxane Cluster Chemical Identity CAS Reg. No. Siloxane Chain Length Molecular Formula Molecular Weight (g/mol) Requested Inert for 40 CFR 180.920 Approval 70280 - 68 - 1 Si - 3 C 13 H 34 O 5 Si 3 354.67 Proposed Siloxane Cluster for Read - Across 107 - 46 - 0 Si - 2 C 6 H 18 OSi 2 162.38 107 - 51 - 7 Si - 3 C 8 H 24 O 2 Si 3 236.54 1873 - 88 - 7 Si - 3 C 7 H 22 O 2 Si 3 221.50 141 - 62 - 8 Si - 4 C 10 H 30 O 3 Si 4 310.29 70131 - 67 - 8 Si - 4 C 8 H 26 O 5 Si 4 314.64 141 - 63 - 9 Si - 5 C 12 H 36 O 4 Si 5 384.85 II. INERT INGREDIENT PROFILE A. Summary of Uses Siloxanes are commonly used in consumer products and as industrial chemicals as either building blocks for other silicone products or as adjuvants/surfactants in shampoo, cosmetics and paints.8

B. Physical Chemical Properties Some of the physical and chemical characteristics of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t rramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , along with its structure and nomenclature, are found in Table 2 along with the cluster chemicals . The physicochemical properties/trends for the Si - 2 to Si - 5 cluster of structurally related linear siloxanes were analyzed utilizing EPA EPISuite 4.1. Overa ll it can be concluded that the proposed cluster of siloxane molecules exhibits the expected physicochemical trends for increasing/decreasing vapor pressure and log K ow that are directly affect by silicon chain length and the increased addition of alkyl si licon substituents or OH groups.Table 2 . Physical and Chemical Properties of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t rramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals

CAS Reg. No. Structure Siloxane Number Log

Kow Vapor

Pressure (mm HG, @25C) Water

Solubility (mg/L) BCF

(Regression L/KG wt/wt) Atmospheric

Oxidation OH Radicals (1/2 life 12 hrs days) Log

Koc Biowin 3:Ultimate (measured in weeks to months) Biowin 4:

Primary (measured in days to weeks) Henry’s

Law Atm m 3 /mole Ultimate Fugacity

Mass (percent)/Half - life (hrs) Requested Inert for 40 CFR 180.920 70280 - 68 - 1 Si - 3 5.7 0.000000378 0.03245 2701 0.306 1.98 2.73 3.58 2.03E 008 Air: 0.137/7.35

Water: 20.3/900 Soil: 79.4/1.8e+003 Sediment: 0.128/8.1e+003 Proposed Siloxane Cluster for Read - Across 107 - 46 - 0 Si - 2 5.3 39.1 0.92 1349 11.92 2.53 2.84 3.62 3.04E 001 Air: 42.9/186

Water:45.3/360 Soil: 11.2/720 Sediment: 0.647/3.24e+004 107 - 51 - 7 Si - 3 6.7 3.49 0.027 10510 8.94 3.42 2.68 3.51 4.18E 001 Air: 39.1/214

Water: 52.9/900 Soil: 1.38/1.8e+003 Sediment: 6.65/8.1e+003 1873 - 88 - 7 Si - 3 6.1 2.7 0.178 5355 10.24 3.26 2.71 3.53 3.03E 001 Air: 39.5/245

Water: 48.5/900 Soil: 7.38/1.8e+003 Sediment: 4.63/8.1e+003 141 - 62 - 8 Si - 4 8.2 0.486 0.0029 3397 7.15 4.31 2.51 3.40 5.74E 001 Air: 21.3/172

Water: 68.3/900 Soil: 1.28/1.8e+003 Sediment: 9.09/8.1e+003 70131 - 67 - 8 Si - 4 4.7 0.0000353 3.017 545.8 1.321 4.312 2.50 3.39 3.00E 008 Air: 0.157/31.7

Water:10.3/900 Soil: 77.5/1.8e+003 Sediment: 12.1/8.1e+003 141 - 63 - 9 Si - 5 9.6 0.0704 0.00006603 697.3 5.96 5.202 2.35 3.29 7.89E 001 Air: 7.51/143

Water: 36.9/900 Soil: 53.95/1.8e+003 Sediment: 1.711/8.1e+003III. HUMAN HEALTH ASSESSMENT

A. Summary of Data T he proposed inert ingredient (CAS Reg. No. 70280 - 68 - 1) was non - toxic via acute oral (MRID 49333603) and acute dermal exposures (MRID 49333604) and was negative for mutagenicity in the Ames assay (MRID 49333605). Based on the weight of evidence from the bridging/read - across analysis o f the linear short chain siloxane cluster (Si - 2 to Si - 5), the proposed inert ingredient is expected to be non - toxic via acute inhalation exposure, non - irritating to the eyes and skin, and not result in skin sensitization. The target organ relevant to mamma lian toxicity for the proposed inert is expected to be the liver, in the form of protoporphyrin accumulation upon repeated dose oral exposure. No carcinogenicity, genotoxicity, reproductive toxicity, developmental toxicity, or neurotoxicity is anticipated with dietary exposure with the proposed inert ingredient . Acute Oral Toxicity In an acute o ral toxicity study (MRID 49333603) in female rats the LD 50 > 2000 mg/kg . No mortality was observed . Clinical signs included lowered locomotor activity, prone positi on and soft feces/diarrhea until 3 hours after treatment but recovered on day 1. Acute Dermal Toxicity In an acute dermal toxicity study (MRID 49333604) on male and f emale rats the LD 5 0 > 2,000 mg/kg. No mortality , clinical signs or dermal signs were observed. No gross abnormalities were noted at necropsy. Acute Inhalation No acute inhalation study was available for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , however studies on the sil oxane clusters compounds were provided. CAS Reg. No. 107 - 51 - 7 had the lowest LC 50 value ( >22.6 mg/L ) for acute inhalation. Based on this LC 50 value , 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is not expected to be a concern via acute inhalation route . Acute Eye Irritation No acute eye irritation study was available for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrramethyl 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , however studies on the siloxane clusters compounds were provided. Each of the cluster compounds with acute eye irritation studies concluded they were non - irritating to the eyes . Based on the se conclusions , 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is expected to be non - irritating to the eyes. Acute Dermal Irritation No acute dermal irritation study was available for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , however studies on the siloxane clusters compounds were provided. Each of the cluster compounds with acute11

dermal ittitation studies concluded they were non - irritating to the skin. Based on these conclusions , 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy ] - is not expected to be non - irritating to the skin. Dermal Sensitization No dermal sensitization study was available for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , however studies on the siloxane clusters compounds were provided. Each of the compounds with dermal sensitization studies concluded that they were negative for dermal sensitization. Based on the se conclusions , 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propox y] - is not expected to be a dermal sensitizer. Table 3 . Acute Toxicity Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals CAS Reg. No. Siloxane

Number Acute

Oral LD 50 Acute

Dermal LD 50 Acute

Inhalation LC 50 Skin

Irritation Eye

Irritation Skin

Sensitization Requested Inert for 40 CFR 180.920 Approval 70280 - 68 - 1 Si - 3 > 2000 mg/kg > 2000

mg/kg N/A N/A N/A N/A Proposed Siloxane Cluster for Read - Across 107 - 46 - 0 Si - 2 > 16 mL/kg > 2000

mg/kg 106 mg/L Non Irritating Non Irritating Non - sensitizing 107 - 51 - 7 Si - 3 > 2000 mg/kg > 2000

mg/kg > 22.6 mg/L Non Irritating N/A Non - sensitizing 1873 - 88 - 7 Si - 3 > 2000 mg/kg N/A N/A N/A N/A N/A 141 - 62 - 8 Si - 4 N/A > 2000 mg/kg N/A Non Irritating Non Irritating N/A 70131 - 67 - 8 Si - 4 > 5000 mg/kg > 2000

mg/kg > 535 mg/L Non Irritating Non Irritating Non - sensitizing 141 - 63 - 9 Si - 5 N?A > 2000 mg/kg N/A Non Irritating Non Irritating N/A N/A = Not Available Oral Repeat Dose Toxicity - Oral repeated dose toxicity studies are available for the cluster of structurally similar linear short chain (Si - 2 to Si - 5) chemicals, for durations ranging from 28 days up to one year in rats, rabbits and dogs. Oral repeated dose data are presented in Tab le 4 . CAS Reg. No. 107 - 46 - 0 A subchronic oral toxicity study on hexamethyldisiloxane (CAS Reg. No. 107 - 46 - 0) was conducted by dosing the substance daily for 28 consecutive days (main test) and by feeding without dosing for 14 consecutive days thereafter ( recovery test) in male and female Crj:CD(SD) rats (6/sex/group) of 5 weeks of age at the start of dosing. The main test composed of 4 dosing groups of 8, 40, 160 and 640 mg/kg/day and a control group. The recovery test was composed of 2 dosing groups 160 a nd 640 mg/kg/day and another control group. No deaths occurred throughout the study period and no abnormalities in relation with the administration of the substance were observed. Food consumption was decreased and body weight gain was suppressed in male o f 640 mg/kg/day group. In hematological examinations, white blood cell count was increased and mean corpuscular volume and mean corpuscular hemoglobin were decreased in male of 640 mg/kg/day12

group. In blood chemical examinations, GOT, GPT, cholinesterase, γ - GTP, total cholesterol, total protein, total bilirubin and Ca were increased and A/G ratio was decreased in male of 640 mg/kg/day group. In urinalysis, turbid urine and acidized urine in pH were observed in male of 640 mg/kg/day group. Organ weights of t he spleen and the liver were increased in male of 640 mg/kg/day group. In necropsy, apparent spotty pattern of surface in the kidney i n males of 160 mg/kg/day and higher groups, dark brownish change and enlargement in the liver and enlargement of the hepat ic lymph node in male of 640 mg/kg/day group were observed. In histopathological examinations, bile stasis, cell infiltration around bile stasis and swelling of hepatocytes in the liver in both sexes of 640 mg/kg/day group, increase of eosinophilic bodies in the kidney in males of 40 mg/kg/day and higher groups, bile duct proliferation, single cell necrosis and increase of mitoses of hepatocytes in the liver and deposition of brown pigment and increase of histiocytic cells in the hepatic lymph node in male of 640 mg/kg/day group were observed. At the end of the recovery period, increase of platelet count and IP, and decreases of hemoglobin concentration and hematocrit value were observed in male of 640 mg/kg/day group. Increases of white blood cell count, to tal cholesterol, spleen weight and liver weight were still observed in male of 640 mg/kg/day group. In histopathological examinations, swelling of hepatocytes, increase of mitoses of hepatocytes, single cell necrosis in the liver and increase of eosinophil ic bodies in the kidney were convalescing but some changes corresponding to bile stasis in the liver were still observed. The NOAEL of CAS Reg. No 107 - 46 - 0 was considered to be 8 mg/kg/day and LOAEL of 40 mg/kg/day based on an increase of eosinophilic bodi es observed in the kidney in males . (EPA 1995) CAS Reg. No. 107 - 51 - 7 In a 28 - day repeat dose oral toxicity study (OECD Guideline 407) o ctamethyltrisilo x ane (CAS Reg. No. 107 - 51 - 7) was administered to Sprague - Dawley rats, orally by gavage at dose levels of 0, 25, 250 or 1000 mg/kg/day for 28 days (5/sex/dose). This study also included control and high dose satellite groups for a 14 day recovery study (5/sex/dose). There were no treatment related effects reported on mortality, clinical effects, food consumpt ion, functional observational battery (FOB) or locomotor activity endpoints. The LOAEL for this study is 250 mg/kg/day based on increases in absolute liver weights, hepatocellular hypertrophy and protoporphyrin accumulation with associated bile duct prolif eration and periportal chronic inflammation in males. After the 14 - day recovery period, hepatocellular hypertrophy showed complete regression while brownish pigment accu mu lation and periportal chronic inflammation were still present in both sexes at 1000 mg/kg/day. Bile duct proliferation persisted only in high dose males. An increased incidence of alpha - 2μ - globulin was seen at all dose levels. The NOAEL for this study is 25 mg/kg/day. (EPA 201 1) CAS Reg. No. 1873 - 88 - 7 In an oral combined repeated dose toxicity / reproductive developmental screening stu dy (OECD Guideline 407 and 422) , 1,1,1,3,5,5,5 - heptamethyltrisiloxane (CAS Reg. No. 1873 - 88 - 7) was administered orally by gavage to 10 HanRcc: W IST(SPF) rats/sex/dose at 0, 50, 200 or 800 mg/kg/day. Animals were dosed during pre - mating, mating, gestation until lactation day 4 (females). Males were dosed for 5 weeks and females for 6 - 8 weeks.13

There were no treatment related effects reported on mort ality, clinical effects, functional observational battery (FOC), grip strength or locomotor activity endpoints. The LOAEL in this study was reported as 200 mg/kg/day based on reduced body weight/body weight gain in males, increased absolute and relative we ights of the liver in males, alpha 2μ globulin nephropathy effects in males, liver centrilobular hypertrophy in 3/5 females, minimal to slight diffuse thyroid follicular cell hypertrophy was o bserved in 2/5 females, and an incr e ase in extramedullary hemato poiesis in females. The NOAEL w a s identified as 50 mg/kg/day. (Ceccatelli 2010) CAS Reg. No. 141 - 62 - 8 In a 28 - day oral toxicity study in rats (OECD Guideline 407) dosed with decamethyltetras iloxane (CAS Reg. No. 141 - 62 - 8). The test material was administer ed orally by gavage to Sprague - Dawley rats at 0, 25, 250, or 1000 mg/kg/day (5/sex/dose). An additional 5 rats/sex/dose were included in the 0 and 1000 mg/kg/day dose groups for a 14 - day recovery period. The LOAEL in this study was identified as 250 mg/kg /day based on minimum protoporphyrin accumul ation at a dose level 250 mg/kg /day in male rats. The severity and incidence of this effect did not decrease at the high dose level after the 14 - day recovery period. An increased incidence and severity of perilob ular fatty change was noted at all dose levels female rats. The severity of the perilobular fatty changes were mild at 25 (5/5, severity = 1.2) and 250 mg/kg /day (5/5 severity = 1.8) and also present in control (3/5 (severity = 1). Effects at the high dose level females (5/5, severity = 2.8) demonstrated a reduction in severity and occurrence (4/5, severity = 1.5). Based on the reduction in the incidence and severity of th e effect at 1000 mg/kg /day in the recovery group at the high dose level, the minimal e ff ects seen at 25 and 250 mg/kg /day were not considered adverse. The authors of the study considered that the periportal fatty change was not accompanied by degeneration or inflammation and was considered to be non - adverse. The NOAEL in this study has been identified as 25 mg/kg/day based on t he presence of based on minimum protoporp hyrin accumulation at 250 mg/kg /day dose in male rats. ( EPA 2009 ) In an 8 - month oral repeated dose toxicity study in albino rabbits, decamethyltetrasiloxane (CAS Reg. No. 141 - 6 2 - 8) was administered via the diet at dose levels of 0 or 1% (3/sex/dose). The NOAEL was identified as 1% or 500 mg/kg /day (the highest dose tested). ( ECHA 2014 ) In a one - year oral repeated dose toxicity study in albino weanling rats, decamethyltetrasiloxane was administered via the diet at dose levels of 0 or 1% (5/sex/dose). The NOAEL wa s identified as 1% or 500 mg/kg /day (the highest dose tested). (ECHA 2014) CAS Reg. No. 70131 - 67 - 8 In the 90 - day oral repeated dose study with Beagle dogs (4/sex/dose), CAS Reg. No. 70131 - 67 - 8 was administered orally in the diet at dose levels of 0%, 0.05%, 0.2% or 1.0% for 90 days. The LOAEL in this study was 0.2% based on increased relative liver weight in 3/4 females and lower relative testes weight s in 2/4 males with slight testicular atrophy or hypoplasia in 1/4 males. The NOAEL in this study is 0.05%, estimated to be14

24 mg/kg/day in males and 25 mg/kg/day in females based on the food consumption data included in the study. (EPA 1994) In a one - ye ar chronic oral rat study with CAS R eg. N o. 70131 - 67 - 8, the test material was administered orally in the diet to albino weanling rats of the FDRL - strain (5/sex/dose level in treatment groups and 10/sex/dose in the control group) at dose levels of 0% or 0.0 5% for one year. No treatment related effects were reported at 0.05 %, estimated to be 27.1 mg/kg /day in males and 30.9 mg /kg /day in females based on the food consumption data included in the study. (Fancher 1968) CAS Reg. No. 141 - 63 - 9 In a 28 - day repeat dose oral toxicity study (OECD Guideline 407), dodecamethylpentasiloxane (CAS Reg. No. 141 - 63 - 9), Sprague - Dawley rats (5/sex/dose) were administered the test material orally via gavage at dose levels of 0, 25, 250, or 1000 mg/kg/day. An additional 5 rats/sex/dose were included in the 0 and 1000 mg/kg/day dose groups for a 14 - day recovery period. Functional observational battery, locomotor activity and grip strength were performed during week 4. In males treated with 1000 mg/kg/day, the me an locomotor activity during 0 - 10 minutes was significantly increased when compared with the control males. Females were unaffected at this dose. Minor transient differences in the mean locomotor activity in males at 1000 mg/kg/day were considered to be un related to the test substance. Mean absolute and relative liver weights were increased in male and females rats at dose levels of 250 mg/kg/day and above; this effect is considered to be adaptive and non - adverse as well as reversible after the 14 - day recov ery period. Higher mean levels of alpha - 2μ - globulin in the kidneys of male rats at 250 and 1000 mg/kg/day were not considered to be relevant to humans. Although histopathological findings of periportal hepatocellular vacuolation were seen at all dose level s in female animals, all histopathological effects were reversible after the 14 - day recovery period. The NOAEL is 1000 mg/kg /day, the highest dose tested. (EPA 2009) Table 4 . Oral Repeated Dose Toxicity Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethy l - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals expressed in mg/kg/day CAS Reg. No. Siloxane

Number 28 - Day Rat (Gavage) 90 - Day Dog (Diet) 8 - Month Chronic Rabbit (Diet) 1 - Year Chronic Rat (Diet) NOAEL LOAEL NOAEL LOAEL NOAEL LOAEL NOAEL LOAEL

Requested Inert for 40 CFR 180.920 Approval 70280 - 68 - 1 Si - 3 N/A N/A N/A N/A Proposed Siloxane Cluster for Read - Across 107 - 46 - 0 Si - 2 160 640 N/A N/A N/A 107 - 51 - 7 Si - 3 25 250 N/A N/A N/A 1873 - 88 - 7 Si - 3 50 200 N/A N/A N/A 141 - 62 - 8 Si - 4 25 250 N/A 500 (HDT) N/A 500 N/A 70131 - 67 - 8 Si - 4 N/A 24 77 N/A 27 (HDT) N/A 141 - 63 - 9 Si - 5 > 1000 N/A N/A N/A N/A N/A = Not Available HDT = Highest Dose Tested Dermal Repeat Dose Toxicity Dermal repeated dose toxicity studies are available for the cluster of structurally similar linear short chain (Si - 2 to Si - 5) chemicals. Dermal repeated dose data are presented in Table 5 .15

CAS Reg. No. 107 - 46 - 0 In an 28 - day repeat dose dermal toxicity stu dy ( OECD Guideline 410 ) , hexamethyldisiloxane ( CAS R eg. N o. 107 - 46 - 0 ) , 10 Sprague - Dawley rats/sex/dose were treated dermally (fur clipped as necessary) in the dorsal area corresponding to 10% of the dermal surface area with 0, 100, 500 or 1,000 mg/kg/day hexamethyldisiloxane applied for 6 hours per day, 5 days per week for a period of 28 days. No mortality, clinical effects were reported. No significant effects were observed in female rats. A slight but statistically significant decrease in body weight gai ns and a decrease in food consumption were observed in the high dose males during the last week of the study. Additionally, a statistically significant decrease in liver and kidney weights was noted in the high dose males when expressed as organ to brain w eight ratio. No adverse changes in chemistry or histopathology were observed in both males and females. The NOAEL for hexamethyldisiloxane in males was considere d to be 500 mg/kg /day, based on reduced kidney and liver weights. There were no such e ffects in females. Overall, the NOAEL is considered to be > 1000 mg/kg /day for human relevant effects. The kidney effects have been proven in other studies to be rela ted to species - specific alpha 2μ - globulin mediated effects. Effects on liver weights were not accom panied by histopathological findings and were not observed in females, therefore are not considered of toxicological significance. (ECHA 2014) CAS Reg. No. 141 - 62 - 8 In an 28 - day repeat dose dermal toxicity study, decamethyltetrasiloxane ( CAS R eg. N o. 141 - 62 - 8 ) , a NOAEL of 1000 mg/kg /day based on no significant adverse effects with respect to body weight, mortality and behavioral reactions and no evidence of testicular atrophy and reduced testicular function in male New Zealand albino rabbits (10 per group) expose d dermally to 0 or 1000 mg/kg /day, once daily, for 28 consecutive days. Table 5 . Dermal Repeated Dose Toxicity Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals expressed in mg/kg/day CAS Reg. No. Siloxane Number 28 - Day Rat 28 - Day Rabbit NOAEL LOAEL NOAEL LOAEL Requested Inert for 40 CFR 180.920 Approval 70280 - 68 - 1 Si - 3 N/A N/A Proposed Siloxane Cluster for Read - Across 107 - 46 - 0 Si - 2 1000 (HDT) N/A N/A 107 - 51 - 7 Si - 3 N/A N/A 1873 - 88 - 7 Si - 3 N/A N/A 141 - 62 - 8 Si - 4 N/A 1000 (HDT) N/A 70131 - 67 - 8 Si - 4 N/A N/A 141 - 63 - 9 Si - 5 N/A N/A N/A = Not Available HDT = Highest Dose Tested Inhalation Repeat Dose Toxicity Inhalation repeated dose toxicity studies are available for the cluster of structurally similar linear short chain (Si - 2 to Si - 5) chemicals. Inhalation repeated dose data are presented in Table 6 . CAS Reg. No. 107 - 46 - 0 In a 28 - day repeated dose inhalation study with hexamethyldisiloxane ( CAS Reg. No. 107 - 46 - 0), Fischer 344 rats (10/sex/dose group) were exposed via nose - only for 616

hours/day, 5 days/week for 4 weeks to concentrations of 0, 136, 513, 1918 or 8939 ppm equivalent to 0.95, 3.38, 12.75 and 59.26 mg/L ) hexamethyldisiloxane . One female in the highest dose group died after the twentieth exposure, the cause of death was not determined. Ophthalmic parameters were unchanged in treated animals compared to pretreatment observations. Slight hematological differences were observed i n the males and females of the highest exposure group. Higher levels of serum cholesterol were observed in females in the 513 ppm (3.38 mg/L) group and males and females in the 2 highest exposure groups; triglycerides were increased in males exposed to 191 8 ppm (12.75 mg/L) and males and females exposed to 8939 ppm (59.26 mg/L); phospholipids were increased in 1918 ppm (12.75 mg/L) group females and 8939 ppm (59.26 mg/L) group males and females; and phosphorus was increased in females of all groups and in m ales of the 513, 1918, and 8939 ppm (3.38, 12.75, and 59.26 mg/L) groups. Decreased calcium levels were reported for males and females in the two highest exposure groups. Individual sexes exhibited similar effects in the 513 and 1918 ppm (3.38, 12.75 mg/L) groups, with only the females of the 136 ppm (0.95 mg/L) group having an increased phosphorus level. Other effects noted in the clinical chemistry were not considered to be toxicologically significant. The urine of the males of the 1918 ppm (12.75 mg/L) e xposure group and both sexes of the highest exposure group had a lower pH. Upon necropsy there was a slight increase in the lung weights of the highest exposure group, increase in liver weights of the males in all of the exposed groups and the females of t he two highest exposure groups and decreases in the thymus weights in the highest exposure group and the ovaries of the females of the highest exposure group. Gross examination of tissues/organs revealed no effects attributable to the test substance. Histo pathological examination revealed an increase in incidence and severity of local inflammatory lesions in the lungs (interstitial inflammation, alveolar macrophage accumulation and leukocyte infiltration) of the highest exposure group, with slight increases in 136, and 1918 ppm groups, but not at 513 ppm. There was also an increase in the incidence and severity of renal tubule degeneration in male rats of the two highest exposure groups; hyaline drople t accumulation, protein casts and granular casts were not ed in the kidneys of the highest exposure group. Minimal hepatocellular hypertrophy was evident in males of the two highest exposure groups and in one female of the highest exposure group; there was increased pigment accumulation in the bile ducts in the h ighest exposure group males. A NOAEC could not be determined as clinical chemistry and pathologic changes in the lungs occurred at all concentrations from 100 to 10,000 ppm (nominal) (136 to 8939 ppm; measured). The nominal LOAEC was 100 ppm (0.67 mg/L); t he LOAEC expressed as a measured concentration is 136 ppm (0.91 mg/L). For this cluster analysis, the common effect is the protoporphyrin accumulation. Therefore for the cluster analysis and read - across the NOAEC is set at 12.75 mg/L and the LOAEC at 59.26 mg/L based on the increased pigment in the bile duct in the high dose males. (OECD 2014) In a 90 - day whole body vapor inhalation study with CAS R eg. N o. 107 - 46 - 0 in rats, the test material was administered to Fischer 344 (F344) rats (20/sex/dose) at nomi nal (actual) concentrations of 0, 50 (50), 200 (194), 600 (593), 1500 (1509) or 5000 (5012) ppm for 6 h/day, 5 days/week for 13 weeks (equivalent to 0.34, 1.3, 4.0, 10.0, and 33.1 mg/L). No treatment - related signs of clinical toxicity or mortality, statist ically significant effects upon body weight gain or food consumption, ophthalmoscopic changes, gross17

macroscopic necropsy findings, or organ weight changes were noted. However, when expressed as organ to body weight ratio, there was an increase in kidney a nd testes weights observed in male rats exposed to 5000 ppm. Minor hematological, clinical biochemical and urinalysis changes were seen but were not considered to be of toxicological relevance. Histological lesions in the kidney apparently consistent with male rat - specific alpha 2 μ - globulin nephropathy were observed in male rats exposed to 593, 1509, and 5012 ppm of HMDS, accompanied by slightly increased plasma urea and creatinine concentrations. No other treatment - related histological changes were seen in exposed rats. The NOAEC for effects relevant to humans was > 5000 ppm (33.2 mg/L). The mg/L value was estimated using the formulation mg/m 3 = (ppm value)(molecular weight)/24.45, the molecular weight of CAS R eg. N o. 104 - 46 - 0 is 162.38. (Cassidy 2001) In a 90 - day nose - only inhalation study with CAS Reg. No. 107 - 46 - 0 in rats, the test material was administered to Fischer 344 rats at concentrations of 0, 0.14, 0.73, 3.12 or 13.64 mg/L for 6 h/day, 5 days/week for 3 months (20/sex/dose). An additional 10 rats /sex/dose were included in the 0 and 13.64 mg/L dose groups for a 30 - day recovery period. Histopathological examination revealed an increase in incidence and severity of multifocal, subpleural, subacute to chronic interstitial inflammation in the lungs in animals of all groups; this effect was slightly increased in the highest exposure group males and in all test material exposed females. After the 1 - month recovery period, this effect was still observed in the exposed animals. Upon necropsy, the males of th e highest exposure group had decreased testes weights; the animals retained for the recovery period did not exhibit these effects. Tubular atrophy of the testes or mucification of the vaginal mucosa was observed in all groups; the testes effect was slightl y increased in the highest exposure group. The testes of two rats in the control group and from five to 11 rats in each of the exposed groups were reduced in size and/or flaccid upon gross examination; this was likely due to the exposure method. The LOAEC in this study was 0.14 mg/L based on lung and testicular effects. A NOAEC was not achieved. For this cluster analysis, the common effect is the protoporphyrin accumulation. Therefore for the cluster analysis and read - across the NOAEC is set at 13.64 mg/L, the highest dose tested. (OECD 2014) In a 1 - year combined chronic toxicity/carcinogenicity study was conducted via whole body inhalation in rats, CAS R eg. N o. 107 - 46 - 0 was administered to Fischer 344 (F344) rats at concentrations of 0, 0.67, 2.7, 10.7 or 33.1 mg/L (0, 100, 400, 1600, and 5000 ppm) for 6 h/day, 5 days/week for 12 or 24 months (20/sex/dose). Non - neoplastic effects included an increase in Leydig cell hyperplasia in males in all exposure groups including controls, which tended to increase in s everity with increasing exposure. An increase in eosinophilic inclusions in the olfactory epithelium in males at all dose levels was attributed to irritant effects. Increased liver weight and intraluminal mineralization in the kidneys were reported in male s at 10.6 mg/L and above. In female rats, a slight reduction in body weight at dose levels of 10.6 mg/L and above was associated with reductions in food consumption. After 12 months of exposure, there was a dose - related increased incidence of Leydig cell t umors (LCTs) in males at all doses (2/20, 10/20, 9/20, 12/20 and 15/20 at 0, 0.67, 2.7, 10.6 and 33.3 mg/L respectively). After 24 months, LCTs were18

observed in almost all males at all dose levels. The high background incidence of LCTs in Fischer 344 rats has been well - known for decades with spontaneous adenomas commonly present at 12 months and their incidence increasing to 75 - 100% by 24 months (Doorman et al., 1990). Also, several renal tubular adenomas and carcinomas occurred in males at 10.6 mg/L (in 3 of 65 animals) and at 33.3 mg/L (in 6 of 65 animals). The renal effects were attributed to male rat specific alpha - 2 μ - globulin mediated nephrotoxicity. No evidence of neoplastic lesions was observed in females after 12 or 24 months. For this cluster analys is, the common effect is the protoporphyrin accumulation. Therefore for the cluster analysis and read - across the NOAEC is set at 33.3 mg/L, the highest dose tested. (ECHA 2014) CAS Reg. No. 107 - 51 - 7 In a 28 - day repeat dose inhalation study (OECD Guideline 422), octamethyltrisiloxane (CAS Reg. No. 107 - 51 - 7), Sprague - Dawley rats (10/sex/group) were exposed via whole body inhalation to 0, 7.74, 15.5 or 31.0 mg/L (actual, 0, 7.7, 15.5 or 31.0 mg/L), 6 h/d ay, 7 days/week, for 28 - 29 days in a combined repeated dose toxicity and developmental/reproductive screening study. There were no test article - related effects on body weight, food consumption, FOB or motor activity parameters. The LOAEC was reported as 7. 7 mg/L based on increased serum cholesterol in males (40% increase over controls). The NOAEC in females was reported as 7.7 mg/L based on an increase in cholesterol in females at 15.5 mg/L. Centrilobular hypertrophy, which was considered an adaptive change , was reported in females exposed to 7.7 mg/L and above and in males exposed at the highest dose. Hepatic protoporphyrinosis was reported in males at 15.5 mg/L and above. (Health Canada 2011) In a 90 - day repeat dose inhalation study (OECD Guideline 413), CAS R eg. N o. 107 - 51 - 7 was administered to male and female Sprague - Dawley rats via whole - body vapor inhalation at concentrations of 0, 95, 400 or 3200 ppm, ( 10/sex/dose) for 6 hours/day (not reported whether exposure was 5 or 7 days/week, equivalent to appr oximately 0.9, 3.9, 31.0 mg/L). The LOAEC was reported to be 3200 ppm (31.0 mg/L) based on accumulation of protoporphyrin crystals in the bile ducts with associated periportal inflammation and bile duct proliferation. In the kidneys tubular hypertrophy was noted and associated with minor changes in salt balance and plasma protein levels. Hyaline droplets noted represented alpha - 2 μ - globulin accumulation. The NOAEC for this study was reported as 400 ppm (3.9 mg/L or 1000 mg/kg/day ). The mg/L values were estim ated using the formulation mg/m 3 = (ppm value)(molecular weight)/24.45, where the molecular weight of CAS R eg. N o. 107 - 51 - 7 is 236.35. (ECHA 2014) CAS Reg. No. 141 - 62 - 8 In a 28 - day repeat dose inhalation study ( OECD Guideline 422 ) study, Sprague - Dawley ra ts (10/sex/group) were exposed via whole - body inhalation to 0 or 400 ppm (5.1 mg/L) for 6 h/day, 7 days/week, for 28 - 29 days in a combined repeated dose toxicity and developmental/reproductive screening study. All animals survived to the scheduled necropsy . There were no clinical signs or effects on body weights and food consumption. No treatment - related changes were observed in any FOB or motor activity parameter. There were no treatment - related alterations in hematology, serum chemistry, organ19

weights, or gan - to - body weight ratios or microscopic examinations of organs/tissues among the groups. Histopathology examinations demonstrated no significant findings. The NOAEC in this study was the highest concentration tested, 5.1 mg/L. In a 90 - day whole body repeat dose inhalation study (OECD Guideline 413), CAS R eg. N o. 141 - 62 - 8 was administered to Sprague - Dawley rats at concentrations of 0, 70 or 400 ppm (10/sex/dose) for a 7 days/week (the hours per day were not reported in the available summary). An addit ional 10 rats/sex/dose were included in the 0 and 400 ppm dose groups for a 30 - day recovery period. There were no clinical signs or treatment - related effects associated with exposure in the ophthalmologic endpoints, body weights, food consumption and rat n eurobehavioral function. Certain changes in serum chemistry and hematology parameters, urinary volumes and organ weights (absolute and relative) may be treatment - related, but not toxicologically significant and/or were within historical control ranges. The only treatment - related microscopic finding in females at 400 ppm was an increased incidence of alveolar macrophages, though not considered an adverse effect. Based on the results of this study the NOAEC for decamethyltetrasiloxane for systemic toxicity in male and female rats is at least 400 ppm (5.1 mg/L). The mg/L value was estimated using the formulation mg/m 3

- (ppm value)(molecular weight)/24.45, the molecular weight of CAS R eg. N o. 141 - 62 - 8 is 310.69. Table 6 . Inhalation Repeated Dose Toxicity Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals expressed in mg/L CAS Reg. No. Siloxane

Number 28 - Day Rat 90 - Day Rat 1 - Year Combined Rat Chronic Toxi city/Carcinogenicity NOAEC LOAEC NOAEC LOAEC NOAEC LOAEC

Requested Inert for 40 CFR 180.920 Approval 70280 - 68 - 1 Si - 3 N/A N/A N/A Proposed Siloxane Cluster for Read - Across 107 - 46 - 0 Si - 2 12.75* A 59.26* A 13.64* B (HDT) N/A* B 33.3* N/A* C 33.2** (HDT) N/A** 107 - 51 - 7 Si - 3 7.7 (females) N/A (males)** 15.5 (females)

7.7 5(males)** 3.9** 31.0** N/A 1873 - 88 - 7 Si - 3 N/A N/A N/A 141 - 62 - 8 Si - 4 5.1** (HDT) N/A 5.1** (HDT) N/A N/A 70131 - 67 - 8 Si - 4 N/A N/A N/A 141 - 63 - 9 Si - 5 N/A N/A N/A N/A = Not Available HDT = Highest Dose Tested * nose only exposure * * whole body exposure A NOAEC and LOAEC are for liver effects, irritative lung effects were seen at all dose levels. B NOAEC and LOAEC are for liver effects, irritative lung effects and testicular effects were s een at all dose levels. C NOAEC and LOAEC are for liver effects, lung effects were considered to be irritative and Leydig cell tumors were found at all dose levels, including controls. In addition to these subchronic toxicity studies, a DEREK analysis on the proposed inert, CAS RN 70280 - 68 - 1, was also conducted. The results of the DEREK analysis include the following structural alerts and probabilities  Hepatotoxicity in mammals is plausible (Organosilicon compound)20  Nephrotoxicity in mammals is equivocal (Organosilicon compound) Based on the toxicological database for the linear short chain siloxane compounds, the nephrotoxicity alert is supported by the available read - across data for both ingestion, dermal and inhalation routes of exposures. However, the nephrotoxic effects are limited to alpha - 2 μ - globulin nephropathy in male rats, which is not relevant to humans. Based on the data available in the read - across analysis, the hepatotoxicity alert is supported by the available data for the ingestion and inha lation routes of entry. In the linear short chain siloxane compounds toxicological database, progressive damage including inflammatory effects, hepatocyte necrosis, cirrhosis, and/or fibrosis were not demonstrated upon chronic exposure. (Holsappie et al. 2 006) Genotoxicity The genotoxicity of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetrtramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and structurally related compounds is given in Table 7 below. Table 7 . Genotoxicity Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tertramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals CAS Reg. No. Siloxane

Number In Vitro Genotoxicity In Vivo Genotoxicity

Ames Assay OECD 471 Mammalian Mutation

OECD 476 Chromosome

Aberration OECD 473 Bone Marrow Micronucleus OECD 475 Requested Inert for 40 CFR 180.920 Approval 70280 - 68 - 1 Si - 3 Negative N/A N/A N/A Proposed Siloxane Cluster for Read - Across 107 - 46 - 0 Si - 2 Negative Negative Negative Negative 107 - 51 - 7 Si - 3 Negative Negative (without activation) Positive (with activation) Negative N/A 1873 - 88 - 7 Si - 3 Negative N/A Negative N/A 141 - 62 - 8 Si - 4 Negative Negative N/A N/A 70131 - 67 - 8 Si - 4 Negative Negative N/A N/A 141 - 63 - 9 Si - 5 Negative N/A N/A N/A Carcinogenicity The data available on the cluster of chemicals covers acute toxicity, repeated dose toxicity, genotoxicity, chronic toxicity and carcinogenicity, as well as reproductive and developmental toxicity. In addition to read - across, a DEREK analys is on the proposed inert, CAS RN 70280 - 68 - 1, was conducted. Based on the toxicological database for the linear short chain siloxane compounds there were no structural alerts for carcinogenicity. A carcinogenicity study is available on one structurally - re lated short chain siloxane compound An increase incidence of Leydig cell tumors (LCTs) in males w as observed at all doses. However, due to the high background incidence of LCTs in Fischer 344 rats, this effect has been determined to not be treatment - relat ed. Renal tubular adenomas and carcinomas were also observed in the study but are attributable to ma l e rat specific alpha 2μ - globulin mediated nephrotoxicity and therefore not relevant to cancer risk concerns in humans.21

Reproductive and Developmental Toxicity CAS Reg. No. 107 - 46 - 0 In a two - generation reproductive toxicity study (OECD Guideline 422) , m ale and female Sprague - Dawley rats (30 sex/group) were exposed to whole - body inhalation treatments of 100, 400, 1600 or 5000 ppm (equivalent to 0.67, 2. 7, 10.6 and 33.1 mg/L) for 6 hours/day, 7 days/week to CAS Reg. No. 107 - 46 - 0 for at least 70 consecutive days prior to mating. Each surviving F 0 and F 1 parental animal received a complete detailed gross necropsy and selected organs were weighed. Daily obse rvations included appearance, behavior, moribundity and mortality. For all F l females in the control and high exposure group, daily estrous cycles (beginning 21 days to pairing) and ovarian primordial follicle counters were recorded. Weekly observations in cluded body weights and food consumption for females in th e F 0 and F l generations. Litter examinations in F l , F 2 and F 3 offspring included fetuses, sex, still births, runs, survival, litter viability and death. Additional behavioral endpoints (surface - righ ting, air - righting, reflexes, FOB, auditory startle response, locomotor activity and/or learning memory assessments) were conducted on F 2 generation pups. Postmortem examinations of all surviving male and female parents after litter weaning and F l and F 2 p ups (non - selected for pairing) included organ weights and gross necropsy of cervical, thoracic and abdominal viscera, histopathology and weights of adrenal glands, brain, epididymis, kidneys, liver, lungs, ovaries, pituitary glands, prostate gland, seminal vesicles with coagulating glands and accessory fluids, spleen, testes, thyroid gland, uterus with oviducts, cervix, vagina, vas deferens. Reproductive indices included days between pairing and coitus, length of gestation, evidence of parturition difficult ies, mating, fertility, copulation and conception indices, testicular and epipdidymal sperm counts, sperm production rate, sperm motility and morphology, ovarian primordial follicle count. Offspring viability indices include mean litter size, postnatal sur vival (day 0 to 4), postnatal survival for other intervals up to day 21. Minimal to mild golden - brown pigment in the periportal areas of the liver (6 of 30), as well as periportal sub - acute inflammation (5 of 30) and bile duct hyperplasia (4 of 30) in a s mall number of 5000 ppm group F 0 males were considered test article - related; the pigment was observed in a statistically significant (p<0.05) manner when compared to the control group and appeared with corresponding inflammatory response and bile duct hype rplasia. These findings were not present in F l females at any exposure level. Bile duct hyperplasia was only observed at the 5000 ppm exposure level for F l males (24 of 29) and females (12 of 28). The incidence was statistically significant. Periportal sub acute inflammation was present in F l males at 1600 ppm (9 of 20) and at 5000 ppm (29 of 29). Statistical significance was achieved for both. Periportal sub - acute inflammation was present in F l females at 1600 ppm (2 of 28) and at 5000 ppm (16 of 28) with statistical significance demonstrated only at 5000 ppm. Tissues from the adult F 2 generation were not collected. The NOAEC for reproductive toxicity was 33.1 mg/L (5000 ppm, highest dose tested). The NOAEC for parental system toxicity was 400 ppm (2.7 mg/ L) based on liver effects in F l males and females at 1600 ppm. The NOAEC for offspring toxicity was 400 ppm22

(2.7 mg/L) based on decreased offspring weights at 1600 ppm. The NOAEC for developmental neurobehavioral toxicity was 10.6 mg/L (1600 ppm), based on a lack of habituation exhibited in the locomotor activity assessments at 5000 ppm, delayed attainment of the surface righting response in the 5000 ppm group F 2 females, and decreases in average and peak acoustic startle response on PND 20 in the 5000 ppm group F 2 males and females. The NOAEC for neuropathological endpoints was 5000 ppm (the highest dose tested). ( Health Canada 2011 ) In a one - generation inhalation study (OECD Guideline 415) in rats with CAS R eg. N o. 107 - 46 - 0, Sprague - Dawley rats were expos ed via whole body inhalation at nominal (actual) concentrations of 0, 100 (99), 1000 (1030) or 5000 (5067) ppm for 6 hrs/day, 5 days/week (equivalent to approximately 0, 0.67, 6.6. and 33.1 mg/L). Group size was 24 rats/sex group for the F 0 generation and 60 offspring/sex/group for F l . Premating exposure was at least 28 consecutive days, the mating period was up to 2 weeks or until proof of pregnancy (vaginal plug or sperm in vaginal smear). Females were exposed through gestation day 20 and the F l generatio n was exposed from Lactation Day 5 (LD5) through the day prior to necropsy. No dosing between parturition and LD5. Pups not selected for the F l generation were necropsied on postnatal day 21 and se lect organs were weighed. All F 0 animals were subject to gr oss necropsy and select organs were weighed. Spermatogenic eval uations were performed on all F 0 males. Designated tissues from all F 0 parental animals in the control and 5000 ppm groups were examined microscopically. There were no effects on mortality, cl inical signs, spermatogenic endpoints, reproductive perf ormance or parturition in the F 0 generation. Mean body weight gain and food consumption were slightly reduced in 5000 ppm males during the first week of the study. At necropsy of F 0 animals , absolute and relative to body and brain weight , mean lung weights at 5000 ppm in males were increased compared to controls. A statistically significant increase in relative to body mean liver weight was observed at 5000 ppm in males. Although mean lung and liver we ights were increased in 5000 ppm males, no macroscopic lung or liver findings were observed. Total litter loss was noted for 1, 1, and 2 dams in the 100, 1000 and 5000 ppm dose groups. F l pups were not otherwise affected. The authors concluded that the tes t substance produced transient effects on body weight gai n and food consumption in the F 0 generation at the high dose of 5000 ppm. In addition, a slight but not statistically significant effect on postnatal pup survival was observed for the 5000 ppm group. No untoward effects were observed at 100 and 1000 ppm. The NOAEC for reproductive and offspring toxicity was 5000 ppm (33.1 mg/L), the highest dose tested. The NOAEC for maternal toxicity was 5000 ppm (33.1 mg/L). (OECD 2014) CAS Reg. No. 107 - 51 - 7 In a combined repeated - dose/reproductive/developmental toxicity screening test (OECD Guideline 422), rats (10/sex/concentration) were exposed via whole - body vapor inhalation to octamethyltrisiloxane (CAS Reg. No. 107 - 51 - 7) at 0, 7.74, 15.5 or 31.0 mg/L. Th ere were no test article - related effects on body weight, food consumption, FOB23

or motor activity parameters. Male rats exhibited hyaline droplet nephropathy at all concentrations tested, which was consistent with alpha - 2μ - globulin mediated nephropathy. Bot h sexes showed significantly increased liver weights (females > 7.74 mg/L and males at 31.0 mg/L) and significant increases in serum cholesterol (40% increase in males at all doses; 31% and 40% increase in females at 15.5 and 31.0 mg/L, respectively). Cent rilobular hypertrophy was observed in females exposed to > 7.74 mg/L, and in males exposed to 31.0 mg/L and was considered an adaptive change. Hepatic porphyria was observed in males at concentrations > 15.5 mg/L. Based on increased serum cholesterol, the LOAEC for systemic toxicity in males was 7.74 mg/L and the NOAEC was not established. The NOAEC for females was established at 7.74 mg/L based on increased serum cholesterol. No treatment - related effects were observed in any of the reproductive parameters or developmental endpoints evaluated. Reproductive and developmental parameters evaluated included evidence of mating, pregnancy, gestation length , mean litter size, mean live litter size, mean litter weight, and mean ratio of live births/litter size. (ECH A 2014) In an uterotrophic bioassay (OECD Guideline 440) was conducted on octamethyltris i loxane ( CAS R eg. N o. 107 - 51 - 7 ) in ovariectomized female Sprague Dawley rats exposed via inhalation to 3500 ppm for 6 hours/day for 3 days. Additional groups of anima ls were treated subcutaneously with 17alpha - ethinyl estradio l (EE) (0.3, 1.0 or 3.0 μg/kg /day) or genistein (10, 25, 50 mg/kg /day) followed by whole body inhalation exposure to filtered air for 6 hours/day for three consecutive days. A final group of anima ls was given a combination of the estrogen receptor an tagonist ICI 182,780 (3 mg/kg/day) and EE (3.0 μg/kg /day) as a positive control. All animals were necropsied following the last exposure on the day 3 and the uterus removed and weighed with and without uterine fluid. Uterine luminal and glandular epithelial cell heights were determined by microscopic examination. Positive controls functioned as expected and no uterotrophic effects were observed at the limit dose of octamethyltrisiloxane, including no eff ect on absolute and relative uterine weights and no increases in uterine glandular and luminal cell height relative to the negative control group. Therefore, the NOAEC for octamethyltrisiloxane is > 3500 ppm, equivalent to 33.9 mg/L. (ECHA 2014) CAS Reg. No. 1873 - 88 - 7 In a combined repeated dose/reproductive and developmental screen study (OECD Guideline 422), 1,1,1,3,5,5,5 - heptamethyltrisiloxane (CAS Reg. No. 1873 - 88 - 7 ) was administered orally by gavage to 10 HanRcc: WIST(SPF) rats/sex/dose at 0, 50, 200 or 800 mg/kg /day during pre - mating, mating, gestation and lactation day 4 (females). Males were dosed for 5 weeks and females for 6 - 8 weeks. In the reproductive and developmental toxicity screening portion of the study, males and females were given the tes t substance for two weeks prior to mating. During the mating phase, vaginal smears were taken each morning and examined for the presence of sperm and/or an internal vaginal plug. Histopathological evaluations were conducted for control and high - dose animal s (5/sex/group for reproductive tissues including the ovaries, uterus, prostate, seminal vesicles, testes and epidydimides, stages of spermatogenesis and histopathology of interstitial cell structure). The uterus was excised and the implantation sites and corpora lutea, if present, were counted. Mating, fertility and gestation indices were24

calculated. No test substance related effects were reported on mating, fertility, mean precoital times, conception rate, mean duration of gestation, corpora lutea count, number of implantations, mean post - implantation loss, or reproductive organs. The NOAEL for systemic toxi city was reported as 50 mg/kg /day. The LOAEL for systemic toxic ity was reported as 200 mg/kg /day based on liver and thyroid histopathology. The NOAEL f or reproductive and developmental toxici ty was 800 mg/kg /day. (OECD 2011) CAS Reg. No. 141 - 62 - 8 In a combined repeated dose/reproductive and developmental screen study (OECD Guideline 422), decamethyltetrasiloxane (CAS R eg. N o. 141 - 62 - 8) Sprague - Dawley ra ts (10/sex) exposed via whole body inhalation to 400 ppm (equivalent to approximately 5.1 mg/L) daily over approximately 30 days. Histopathology and organ weights relevant to reproductive toxicity (testes, epidydimides , seminal vesicles and prostate weights, ovaries and oviducts, uterine weights) were assessed on all adult male and toxicity group females. Offspring were examined for number and sex, number of live, dead fetuses and runts, as well as weights and gross exa minations. Postmortem offspring pathology examinations included gross pathology only. Reproductive indices included gestation length, mean number of implantation sites, mean number of corpora lutea, mean mating and fertility indices, mean litter size and w eight. No deaths and no significant treatment - related clinical signs of toxicity were observed. Significant increases in body weight gains were noted in the 400 ppm parental females during the third week of gestation, which were not considered to be trea tment - related. Three female rats in the 400 ppm group with evidence of copulation failed to deliver a litter. One of these three females showed signs of parturition (blood discharge) on gestation day 25, but no pups were found. However, seven implant sites were present. The remaining females produced litters that were similar to the controls. There was no effect on testes or epidydimides weights or other reproductive organs examined. There were no treatment - related effects apparent for any of the reproducti ve endpoints. There were no changes observed in the litter size, male - to - female ratio, pup body weights or the pup survival. There were no differences in absolute organ weights. There appeared to be no functional or neurological effects of the test substan ce on the rats. A NOAEC of 400 ppm (the only concentration tested) was calculated based on general and reproductive toxicity, according to the study report. However, OECD states that it should be noted that three/ten female rats in the treated group with evidence of copulation failed to deliver a litter. One of these three females showed signs of parturition (blood discharge) on gestation day 25, but no pups were found. However, seven implant sites were present. The remaining females produced litters that were similar to the controls. (ECHA 2014) Immunotoxicity No i mmunotoxicity studies were available in the database for 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - . However, evidence of immunotoxicity was not o bserved in the available studies.25

Neurotoxicity No neurotoxicity studies were available in the database for 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - . However, evidence of neurotoxicity was not observed in the available studies. Metabolism and Pharmacokinetics There are currently no publically - available metabolism studies for 1,2 - propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , however, relevant expected metabolic pathways can be determined based on metabolism for structurally similar compounds and results obtained from the OECD Tool Box Analysis. The expected mammalian m etabolic pathways involved in the degradation of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is a combination of ether hydrolysis followed by ß - oxidation of the carbon chain followed by methyl oxidation of the silyl methyl groups. Methyl oxidation would result in the formation of a mixture of primary and alcohol metabolites. The more polar primary alcohol functionalities can both be conjugated and excreted directly or further oxidized to form a mixture of more p olar carboxylic acid metabolites that could be readily conjugated and excreted. Table 8 . Toxicology Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals Guideline No./ Study Type Doses

Levels Results MRID No. 28 - day oral toxicity Rat (gavage ) CAS No. 107 - 46 - 0 8, 40, 160

and 640 mg/kg/day NOAEL 160 mg/kg /day

LOAEL 640 mg/kg/day based on an increase of eosinophilic bodies observed in the kidney in males. MRID 49333607 ; Attachment 13 28 - day oral toxicity Rat (gavage) CAS No. 107 - 51 - 7 0, 5, 25, 250

or 1000 mg/kg/day NOAEL 25 mg/kg /day

LOAEL 250 mg/kg/day based on increases in absolute liver weights, helpatocellular hypertrophy and protoporphyrin accumulation with associated bile duct proliferation and periportal chronic inflammation in males. MRID 49333607 ; Attachment 14

28 - day oral toxicity Rat (gavage) CAS No. 1873 - 88 - 7 0, 50, 200 or

800 mg/kg/day NOAEL = 50 mg/kg /day

LOAEL = 200 mg/kg/day based on reduced body weight/body weight gain in males, increased absolute and relative weights of the liver in males, alpha 2μ - globulin nephropathy effects in males, liver centrilobular hypertrophy, minimal to slight diffuse thyroid follicular cell hypertrophy, and an increase in extramedullary hematopoiesis in females. MRID 49333607 ; Attachment s 6 and 15

28 - day oral toxicity Rat (gavage) CAS No. 141 - 62 - 8 0, 25, 250,

or 1000 mg/kg/day NOAEL = 25 mg/kg /day

LOAEL = 250 mg/kg/day based on minimu m protoporphyrin accumulation in males. MRID 49333607 ; Attachment 1626

Table 8 . Toxicology Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals Guideline No./ Study Type Doses

Levels Results MRID No. 28 - day oral toxicity Rat (gavage) CAS No. 141 - 63 - 9 0, 25, 250,

or 1000 mg/kg/day NOAEL = 1000 mg/kg /day

LOAEL = Not Available MRID 49333607 ; Attachment 22 and 23 90 - day oral toxicity Dog (diet) CAS No. 70131 - 67 - 8 0%, 0.05%,

0.2% or 1.0% 0, 24, 77, 414 mg/kg/day NOAEL = 24 mg/kg /day

LOAEL = 77 mg/kg/day based on increased relative liver weight in females and lower relative testes weight in males with slight testicular atrophy or hypoplasia in males. MRID 49333607 ; Attachment 20

8 - month oral toxicity Rabbit (diet) CAS No. 141 - 62 - 8 0% or 1%

0 or 500 mg/kg/day NOAEL = 500 mg/kg /day highest does tested

LOAEL = Not Available MRID 49333607 ; Attachment 1 7 1 - year oral toxicity Rat (Diet) CAS No. 141 - 62 - 8 0% or 1%

0 or 500 mg/kg/day NOAEL = 500 mg/kg /day highest does tested

LOAEL = Not Available MRID 49333607 ; Attachment 17 1 - year oral toxicity Rat (Diet) CAS No. 70131 - 67 - 8 0% or 0.05%

0 or 27 mg/kg/day NOA EL = 27 mg/kg /day highest does tested

LOAEL = Not Available MRID 49333607 ; Attachment 14 28 - day dermal toxicity Rabbit CAS No. 141 - 62 - 8 0 or 1000

mg/kg/day NOAEL = 1000 mg/kg/day highest does tested

LOAEL = Not Available MRID 49333607 ; Attachment 35 28 - day dermal toxicity Rat CAS No. 107 - 46 - 0 0, 100, 500

or 1000 mg/kg/day NOAEL = 1000 mg/kg/day highest does tested

LOAEL = Not Available MRID 49333607 ; Attachment 24 and , 25 28 - day inhalation toxicity Rat CAS No. 107 - 46 - 0 Nose only

exposure 0, 136, 513, 1918 or 8939 ppm 0.95, 3.38, 12.75 or 59.26 mg/L NOAEC = 12.75 mg/ L

LOAEC = 59.26 mg/ L based on increased pigment in the bile duct in the high dose males. MRID 49333607 ; Attachment 24

28 - day inhalation toxicity Rat CAS No. 107 - 51 - 7 Whole body

exposure 0, 7.7, 15.5 or 31.0 mg/L NOAEC (females) = 7.7 mg/L

NOAEC (males) = N/A LOAEC (females) = 15.5 mg/ L based on increased cholesterol LOAEC (males) = 7.7 mg/ L based on increased serum cholesterol MRID 49333607 ; Attachment 327

Table 8 . Toxicology Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals Guideline No./ Study Type Doses

Levels Results MRID No. 28 - day inhalation toxicity Rat CAS No. 141 - 62 - 8 Whole body

exposure 0 or 400 ppm 0 or 5.1 mg/L NOAEC = 5.1 mg/ L highest does tested

LOAEC = Not Available MRID 49333607 ; Attachment 29

90 - day inhalation toxicity Rat CAS No. 107 - 46 - 0 Nose only

exposure 0, 0.14, 0.73, 3.12 or 13.64 mg/L NOAEC = 13.64 mg/ L highest does tested

LOAEC = Not Available MRID 49333607 ; Attachment 24

90 - day inhalation toxicity Rat CAS No. 107 - 46 - 0 Whole body

exposure 0, 50, 194, 593, 1509 or 5012 ppm 0, 0.34, 1.3, 4.0, 10.0 or 33.2 mg/L NOAEC = 33.2 mg/ L highest does tested

LOAEC = Not Available MRID 49333607 ; Attachment 26

90 - day inhalation toxicity Rat CAS No. 107 - 51 - 7 Whole body

exposure 0, 95, 400 or 3200 ppm 0, 0.9, 3.9, 31.0 mg/L NOAEC = 3.9 mg/ L (equivalent to 1000 mg/kg/day)

LOAEC = 31.0 mg/ L based on accumulation of protoporphyrin crystals in the bile ducts with associated periportal inflammation and bile duct proliferation. In the kidneys tubular hypertrophy was noted and associated with minor changes in salt balance and p lasma protein levels. MRID 49333607 ; Attachment 28

90 - day inhalation toxicity Rat CAS No. 141 - 62 - 8 Whole body

exposure 0, 70 or 400 (5.1 mg/L) ppm NOAEC = 5.1 mg/ L highest does tested

LOAEC = Not Available MRID 49333607 ; Attachment 30

1 - year inhalation toxicity Rat CAS No. 107 - 46 - 0 Nose only

exposure 0, 100, 400, 1600 or 5000 ppm 0, 0.67, 2.7, 10.7 or 33.1 mg/L NOAEC = 33.3 mg/ L

LOAEC = Not Available MRID 49333607 ; Attachment 2728

Table 8 . Toxicology Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals Guideline No./ Study Type Doses

Levels Results MRID No. Ames Assay OECD 471 CAS No. 70280 - 68 - 1 Negative MRID 49333605 Ames Assay OECD 471 CAS No. 107 - 46 - 0 Negative MRID 49333607 ; Attachment 3 and 24 Ames Assay OECD 471 CAS No. 107 - 51 - 7 Negative MRID 49333607 ; Attachment 3 and 6 Ames Assay OECD 471 CAS No. 1873 - 88 - 7 Negative MRID 49333607 ; Attachment 6 Ames Assay OECD 471 CAS No. 141 - 62 - 8 Negative MRID 49333607 ; Attachment 33 Ames Assay OECD 471 CAS No. 70131 - 67 - 8 Negative Ames Assay OECD 471 CAS No. 141 - 63 - 9 Negative MRID 49333607 ; Attachment 3 Mammalian Mutation OECD 476 CAS No. 107 - 46 - 0 Negative MRID 49333607 ; Attachment 3 and , 24 Mammalian Mutation OECD 476 CAS No. 107 - 51 - 7 Negative without activation Positive with activation MRID 49333607 ; Attachment 3 and 6 Mammalian Mutation OECD 476 CAS No. 141 - 62 - 8 Negative MRID 49333607 Attachment 3329

Table 8 . Toxicology Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals Guideline No./ Study Type Doses

Levels Results MRID No. Mammalian Mutation OECD 476 CAS No. 70131 - 67 - 8 Negative

Chromosome Aberration OECD 473 CAS No. 107 - 46 - 0 Negative MRID 49333607 ; Attachment 3 and 24 Chromosome Aberration OECD 473 CAS No. 107 - 51 - 7 Negative MRID 49333607 ; Attachment 3 and 6 Chromosome Aberration OECD 473 CAS No. 1873 - 88 - 7 Negative MRID 49333607 ; Attachment 6

Bone Marrow Micronucleus OECD 475 CAS No. 107 - 46 - 0 Negative MRID 49333607 ; Attachment 3 and 24 Reproductive and Developmental Toxicity (gavage) OECD 422 CAS No. 1873 - 88 - 7 0, 50, 200 or

800 mg/kg/day NOAEL (systemic) = 50 mg/kg/day

LOAEL (systemic) = 200 mg/kg/day based on liver and thyroid histopathology. NOAEL (developmental) = 800 mg/kg/day highest does tested LAOEL (developmental) = Not Available MRID 49333607 ; Attachment 6 and 1530

Table 8 . Toxicology Profile of 1,2 - propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals Guideline No./ Study Type Doses

Levels Results MRID No. Reproductive and Developmental Toxicity (whole body inhalation) OECD 422 CAS No. 107 - 46 - 0 0, 100, 400,

1600 or 5000 ppm Equivalent to: 0.67, 2.7, 10.6 and 33.1 mg/L NOAEC (parental) = 2.7 mg/L

LOAEC (parental) = 10.6 mg/L based on liver effects in F1 males and females NOAEC (repro) = 33.1 mg/L highest does tested LOAEC (repro) = Not Available NOAEC (develop - neuro behavioral ) = 10.6 mg/L LAOEL (develop - neurobehavioral ) = 33.1 mg/L based on lack of habituation in locomotor a ctivity, delayed attainment of surface righting response of F2 females and decreases in average and peak acoustic startle response on PND 20 in F2 males and females NOAEC (neuropathological) = 33.1 mg/L highest does tested LOAEC (neuropathological) = Not Available MRID 49333607 : Attachment 3 and 24

Reproductive and Developmental Toxicity (whole body inhalation) OECD 422 CAS No. 107 - 51 - 7 0, 7.74, 15.5

or 31.0 mg/L NOAEC (males) = N/A

LOAEC (males) = 7.74 mg/L based on increased serum cholesterol NOAEC (females) = 7.74 mg/L LOAEC (females) = 15.5 mg/L based on increased serum cholesterol NOAEC (developmental/reproductive) = 31.0 mg/L highest does tested LOAEC (developmental/reproductive) = N/A MRID 49333607 : Attachment 3 and 6

Reproductive and Developmental Toxicity (whole body inhalation) OECD 422 CAS No. 141 - 62 - 8 400 ppm

5.1 mg/L NOAEC (parental) = 5.1 mg/L highest dose tested

LOAEC (parental) = N/A NOAEC (repro/developmental) = 5.1 mg/L highest dose tested LOAEC (repro/developmental) = N/A MRID 49333607 : Attachment 23 Uterotrophic Bioassay rat OECD 440 CAS No. 107 - 51 - 7 3500 ppm

33.9 mg/L NOAEC = 33.9 mg/L highest dose tested

LOAEC = N/A MRID 49333607 : Attachment 32

B. Toxicity Endpoint Selection The 28 day studies in rats (CAS Reg. No. 107 - 51 - 7 and 141 - 62 - 8) The NOAEL was 25 mg/kg/day with a LOAEL 250 mg/kg/day based on based on increases in absolute liver weights, helpatocellular hypertrophy and protoporphyrin accumulation with associated bile duct proliferation and periportal chronic i nflammation. A 90 - day dog study had a NOAEL of 24 mg/kg/day with a LOAEL of 77 mg/kg/day based on increased relative31

liver weight in females and lower relative testes weight in males with slight testicular atrophy or hypoplasia in males. A NOAEL of 25 was selected for use as the endpoint for dietary exposure in this risk assessment. Dermal and inhalation exposure endpoints were not selected because there are sufficient studies provided that show no adverse effects up to limit dose levels in both rats and rabbits. T able 9 . Summary of Toxic ological Doses and Endpoints of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tertramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and cluster chemicals for Use in Human Health Risk Assessment Exposure/Scenario Point of Departure and Uncertainty/Safety Factors RfD, PAD, LOC for Risk Assessment Study and Toxicological Effects Acute dietary (General population including infants and children) An acute effect was not found in the database therefore an acute dietary assessment is not necessary. Chronic dietary (All populations) NOAEL= 25 mg/kg/day UF A = 10 x UF H = 10 x FQPA SF = 3 x Chronic RfD = 0.08 mg/kg/day cPAD = 0.08 mg/kg/day [ 28 - day oral toxicity - rat ]

LOAEL = 250 mg/kg/day based on protoporphyrin accumulation in the liver. Incidental oral short - term (1 to 30 days) NOAEL= 25 mg/kg/day UF A = 10 x UF H = 10 x FQPA SF = 3 x LOC for MOE = 3 00 [ 28 - day oral toxicity - rat ]

LOAEL = 250 mg/kg/day based on protoporphyrin accumulation in the liver. Incidental oral intermediate - term (1 to 6 months) NOAEL= 25 mg/kg/day UF A = 10 x UF H = 10 x FQPA SF = 3 x LOC for MOE = 3 00 [ 28 - day oral toxicity - rat ]

LOAEL = 250 mg/kg/day based on protoporphyrin accumulation in the liver. Dermal short - term (1 to 30 days) A dermal effect was not found in the database based on a 28 - day dermal study in rat and rabbit therefore a dermal assessment is not necessary. Dermal intermediate - term (1 to 6 months) A dermal effect was not found in the database based on a 28 - day dermal study in rat and rabbit therefore a dermal assessment is not necessary. Inhalation short - term (1 to 30 days) An inhalation effect was not found in the database based on 28 - day and 90 - day inhalation studies in rats therefore an inhalation assessmen t is not necessary. Inhalation (1 to 6 months) An inhalation effect was not found in the database based on 28 - day and 90 - day inhalation studies in rats therefore an inhalation assessment is not necessary. Cancer (Oral, dermal, inhalation) Based on the lack of increased incidence of tumor formation compared to controls in multiple carcinogenicity studies and the lack of mutagenicity therefore a cancer assessment is not necessary . UF A = extrapolation from a nimal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (i ntraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short - term study for long - term risk assessment. UF DB = to account for the absence of data or other data d eficiency. FQPA SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference do se. MOE = margin of exposure. LOC = level of concern. C. Special Considerations for Infants and Children FFDCA, as amended by FQPA, directs the Agency to use an additional 10X safety factor (SF), to account for potential pre - and postnatal toxicity and completeness of the data with respect to exposure and toxicity to infants and children. FQPA authorizes the32

Agency to modify the 10X FQPA SF only if reliable data demonstrate that the resulting level of exposure would be safe for infants and children. EPA concludes that the FQPA saf ety factor could be reduced to 3 X for 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tertramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - for the following reasons: i. The toxicity database for 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tertramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is not complete however based on bridging /read - across analysis of a cluster of structurally similar chemicals, the toxicological database is adequate for characterizing the toxicity of linear short chain siloxane compounds and assessing the risk from dietary exposure to the proposed inert ingredient . ii. Th ere is no evidence of increased quantitative or qualitative susceptibility of rat fetuses to the effects of cluster members. In the oral combined repeated dose and reproductive and developmental screening study with Si3 compound CAS Reg. No. 1873 - 88 - 7, the NOAEL for parental toxicity was 50 mg/kg/day and the developmental toxicity was 800 mg/kg/day (the highest dose tested) indicating no evidence of increased susceptibility. Because the oral route of exposure is most applicable to the dietary risk assessmen t, this study is the most relevant to the assessment of risk resulting from dietary exposure to the proposed inert ingredient. iii. No neurobehavioral or neuropathological effects were reported from oral exposures. The two - generation reproduction study vi a whole - body inhalation with CAS Reg. No. 107 - 46 - 0 did report a NOAEC for developmental neurobehavioral toxicity at 10.6 mg/L (1600 ppm) , based on a lack of habituation exhibited in the locomotor activity assessments at 5000 ppm, delayed attainment of the surface righting response in the 5000 ppm group F 2 females , and decreases in average and peak ascoustic startle response on PND 20 in the 5000 ppm group F 2 males and females. However, these effects were noted at exposure concentrations above the NOAEC for parental systemic toxicity and offspring decreased body weight effects (400 ppm or 2.7 mg/L). iv. There is no indication that 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is an immunotoxic chemical. Although no immunotoxicity studies were available in the database, no signs of immunotoxicity were observed in the available studies. Therefore, there is no need for an immunotoxicity study or additional UFs to account for immunotoxicity. v. The dietary food exposure assessment utilizes proposed tolerance leve l or higher residues and 100% crop treated information for all commodities. 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 can be reduced to 3 X to account for the use of a subchronic study to derive a reference dose .33

IV. EXPOSURE ASSESSMENT

The petitioner has requested use of 1,2 - p ropanediol,3 - [3 - [1,3,3, 3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - with 5 % limitation in pesticide formulation s . The petitioner request ed the ability to use 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - in any type of pesticide , i.e., insecticide, fungicide or herbicide. Therefore, the Agency has conducted a “screening - level” assessment of a wide variety of sites and use patterns in an effort to obtain a qualitative idea of the possible results of human exposures that might result from such combinations of method s of application and site s of application. A. Dietary Exposure: i. Acute exposure . No adverse effects attributable to a single exposure of 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - were seen in the toxicity databases. Therefore, acute dietary risk assessment for 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is not required. ii. Ch ronic 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 National Health and Nutrition Exami nation Survey, What we eat in America, (NHANES/WWEIA). This dietary survey was conducted from 2003 to 2008 . As to residue levels in food, n o residue data were submitted for 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]pro poxy] - . In the 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 given commodity from a list of high - use insecticide s, 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 Polyalkoxylates (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 t olerance 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 of tolerances would be no higher than the concentration of the active ingredien t.34

The Agency believes the assumptions used to estimate dietary exposures lead to an extremely conservative assessment of dietary risk due to a seri es of compounded conservatisms. First, assuming that the level of residue for an inert ingredient is eq ual to the level of residue for the active ingre dient will overstate exposure. The concentration of active ingredients in agricultural products is generally at least 50 percent of the product and often can be much higher. Further, pesticide products rarely have a single inert ingredient; rather there is generally 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. Second, the conservatism of this methodology is compounded by EPA’s decision to assume 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 wit h the highe st tolerance level. This assumption overstates residue values because it would be highly unlikely, 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. Finally, a third compounding conservatism is EPA’s assumption that all foods contain the inert ingredient a t 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 legally poss ible for an active ingredient. In summary, EPA chose a very conservative method for estimating what level of inert residue could be on food, and then use this meth odology to choose the highest possible residue that could be found on food and assumed that al l food contained this residue. No consideration was given to potential degradation between harvest and consumption even though monitoring data shows that toleranc e level residues are typically one to two orders of magnitude higher than actual residues in food when distributed in commerce. Accordingly, although sufficient information to quantify actual residue levels in food is not available, the compounding of th ese conservative assumptions will lead to a significant exaggeration of actual exposures. EPA does not believe that this approach underestimates exposure in the absence of residue data. The addit ional adjustment factor 2 of 0.1 was utilized in thi s analys is to account for the 5 % limitation in formulation. Table 10 . Summary of Chron ic Dietary Exposure and Risk of 1 ,2 - Propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - Population Subgroup cPAD (mg/kg/day) Chronic Exposure (mg/kg/day) %cPAD General U.S. Population 0.08 0. 0 18934 23.7 % All Infants (<1 year old) 0 . 039443 49.3 % Children 1 - 2 years old 0. 070624 88.3 % Children 3 - 5 years old 0. 048563 60.7 % Children 6 - 12 years old 0. 025055 31.3 % Youth 13 - 19 years old 0. 013480 16.8 % Adults 20 - 49 years old 0. 014474 18.1 % Adults 50+ years old 0. 015179 19.0 %35

Females 13 - 49 years old 0. 014633 18.3 % Based on analyses of estimated dietary risks for the general U.S. population and various population subgroups, the chronic dietary exposure estimates for 1 ,2 - Propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - are below the Agency’s level of concern for all supported commodities. The chronic dietary exposure estimate for the highest ex posed population subgrou p, children 1 - 2 years old is 88.3 % of the chronic population adjusted dose (cPAD). The chronic dietary exposure estimate for the general U.S. population is 23.7 % of the cPAD. iii. Cancer exposure . 1 ,2 - Propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is not expected to be carcinogenic based on multiple carcinogenicity studies which showed no increase in incidence of tumors when compared to the controls . Also all genotoxicity studies on 1 ,2 - propa nediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - and structurally - related compounds were negative. Therefore, a cancer dietary exposure assessment is not necessary to assess cancer risk. B. Dietary Exposure from Drinking Water : For the purpose of the screening level dietary risk assessment to support this request for an exemption from the requirement of a tolerance for 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , a conservative drin king 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 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tertramethyl - 1 - [(trimethylsilyl)oxy ] - 1 - disiloxanyl]propoxy] - . These values were directly entered into the dietary exposure model. C. Residential (Non - Occupational) Exposure : The screening - level assessment was conducted using an Antimicrobials Division (AD) assessment tool developed to assess Amine Oxide (“ 900439 , (C10 - 16); C10 - C18 - Alkyldimethylamine oxides; Human Health Risk Assessment and Ecological Effects Assessment to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations.” 22 SEPT 2009; Memorandum L. Austin to P. Shah; Reg. Div./OPP/EPA). The assessment tool uses standard assessment methodology developed by the Antimicrobials Division and the Science Advisory Council for Exposure (EXPOSAC), Health Effects Division/Office of Pesticide Programs. The methodology can also be found in part at: http://www.epa.gov/pesticides/science/residential - exposure - sop.html http://www.epa.gov/pesticides/science/post - app - exposure - data.html http://www.epa.gov/pesticides/science/handler - exposure - data.h tml . In its simplest form, exposure is assessed as follows:36

Unit Exposure * Amount applied/Unit * Units treated/day * absorption factor ÷ Body Wt. (mg/lb handled) (lb applied/unit) (acres etc) kg O ral absorption is assumed to be 100 %. T he maximum concentration of 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tertramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - in a pesticide formulations is no more than 5 %. The result is an estimated average daily d ose (ADD or “exposure” ) expressed as mg material/kg /day. That value is used then to calculate the Margin of Exposure (MOE) (estimated measure of risk). An MOE is calculated by dividing the value of the average daily dose into the toxicological endpoint of concern (also expressed in mg material/kg bw/day). Typically, resulting MOEs ≥ 100 do not exceed the Agency’s level of concern. MOEs less than 100 typically exceed the Agency’s level of concern. For the dietary exposure assessments the Agency uses t he t oxicological endpoint of 25 mg/kg/day identified from the 28 - day oral toxicity study in rats ba sed on protoporphyrin accumulation in the liver. There is no end point of concern selected for dermal or inhalation exposure because no effects were seen in studies on both rats and rabbits up to limit dose. Therefore residential exposure only includes dietary exposure. i. From non - dietary exposure. The term “residential exposure” is used in this document to refer to non - occupational, non - dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). 1,2 - Propanediol,3 - [3 - [1,3,3,3 - te t r amethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - may be used as inert ingredients in pesticide products that are registered for specific uses that may result in indoor or outdoor residential exposures. Possible routes of exposure are expected to be inhalation and dermal exposure as a result of contact with areas treated with 1,2 - propanediol,3 - [3 - [1,3,3,3 - tertramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - . A screening level residential exposure and risk assessment was only completed on child ren hand - to - mouth and object - to - mouth exposure because there are no endpoints of concern for dermal or inhalation toxicity up to the limit dose of 1000 mg/kg/day . Tab le 11 . Residential Post - Application Short - and Intermediate - term Exposures and Risks f or 1 ,2 - Propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - Pesticide Type Exposure Scenario Application Rate 1 Exposed Population &

Exposure Duration 2 Daily Dose (mg/kg/day) 3 MOE 4 Outdoor Products Herbicide Insecticide Fungicide Hand - to - Mouth

from Treated Lawn 0.225 lb/day Child ST 0.003364 7400 Child IT 0.001598 16000 Object - to - Mouth from Treated Lawn Child ST 0.000841 30000 Child IT 0.000841 30000 1 Application rates for maleic anhydride and maleic acid are based on default values provided in the AD assessment tool. Inert ingredient limited to 5% of formulation. 2 ST indicate short - term exposure durations ; IT indicate intermediate - term exposure durations 3 Daily Dose is calculated differently for each exposure scenario. Refer to AD assessment tool for more details. 4 MOE = PoD (NOAEL of 25 mg/kg/day for oral, 1000 mg/kg/day dermal and inhalation )/ Daily dose (mg/kg/day)37

The post - application child (hand - to - mouth) short - term MOE was calculated to be 7400 from treated lawns. The post - application child (object - to - mouth) short - term MOE was calculated to be 30000 from treated lawns. As the level of concern i s for MOEs that are lower than 3 00, these MOEs are not o f concern. V. AGGREGATE RISK ASSESSMENT EPA determines whether acute and chronic pesticide exposures are safe by comparing aggregate exposure estimates to the acute population adjusted dose ( aPAD ) and chronic population adjusted dose ( cPAD ). The aPAD and cP AD represent the highest safe exposures, taking into account all app ropriate safety factors (SFs). EPA calculates the aPAD and cPAD by dividing the POD (i.e. toxicological endpoint) by all applicable UFs. For linear cancer risks, EPA calculates the probabi lity 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 by t he product of all a pplicable UFs is not exceeded. i. Acute Dietary Risk. An acute aggregate risk assessment takes into account exposure estimates from acute dietary consumption of food and drinking water using the exposure assu mptions discussed in S ection IV for acute exposure. However there was no hazard attributable to a single exposure seen in the toxicity database fo r 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - ; therefore there is no concern for an ac ute dietary risk and an acute aggregate risk assessment was not conducted . ii. Chronic Dietary Risk. A chronic aggregate risk assessment takes into account exposure estimates from chronic dietary consumption of food and drinking water using the exp osure a ssumptions discussed in S ection IV from chronic exposure . The chronic analysis was based on a 28 - day oral toxici ty study with a NOAEL of 25 mg/kg/day based on protoporphyrin accumulation in the liver. A chronic dietary risk assessment at the initially - prop osed use limitation of 10% by weight in the pesticide formulation resulted in potential chronic dietary risk of concern. The petitioner subsequently agreed to a use limitation of 5% in the pesticide formulation. The chronic dietary exposure f ro m food and w ater resulting from the use of 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - as an inert ingredient at a concentration not to exceed 5% by weight in pesticides applied to growing crops is 23.7 % of the cPAD for the U.S. population and 88.3 % for children 1 - 2 yrs old , the most highly exposed population subgroup. iii. Aggregate Cancer Risk for U.S. Population. The Agency has not identified any concerns for carcinogenicity relating to 1,2 - p ropanediol,3 - [3 - [1,3,3 ,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - ;38

therefore, a cancer dietary exposure assessment was not performed and an aggregate cancer risk is not a concern . iv. Short - term Aggregate Risk. Short - term aggregate exposure takes into accoun t short - term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). 1,2 - Propanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - may be used as an inert ingredient in pestic ide products that could result in short - term residential exposure. However t he Agency has determined that it is only appropriate to aggregate chronic exposure through food and water with short - term residential exposures for children because there are no en dpoints of concern for residential dermal or inhalation toxicity that would affect adults . EPA has concluded the combined short - term aggregated food, water, and residential exposures results in an aggregate MOE of 334 for children. Children’s aggregate MOE combines average food and water exposure from the chronic dietary exposure with residential exposure associated with contact with treated lawns ( hand - to - mouth + object - to - mouth ). As the level of concern i s for MOEs that are lower than 3 00, these MOEs are not of concern. Table 12 . Short - Term Aggregate Risk Calculations for 1 ,2 - Propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - Population PoD

mg/kg/day LOC 1 Max Allowable Exposure 2 mg/kg/day Average

Food & Water Exposure 3 mg/kg/day Residential

Exposure 4 mg/kg/day Aggregate

MOE (food and residential) 5 Child 25 3 00 0.08 0. 070624 0.004205 334 1 The LOC (Level of Concern) is based on the standard inter - , intra - species uncertainty factors and FQPA SF totaling 3 00. 2 Maximum Allowable Exposure (mg/kg/day) = PoD (Point of Departure)/LOC. 3 Average Food & Water Exposure = Chronic Dietary Exposure Table 5. 4 Residential Exposure = Child ST [HTM +OTM] 5 Aggregate MOE = [PoD/ (Avg Food & Water Exposure + Residential Exposu re)]. v. Intermediate - Term Aggregate Risk. Intermediate - term aggregate exposure takes into account intermediate - term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). 1,2 - Propanediol,3 - [3 - [1,3,3, 3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - may be used as an inert ingredient in pesticide products that could result in intermediate - term residential exposure. However t he Agency has determined that it is only appropriate to aggregate chronic exposure t hrough food and water with intermediate - term residential exposures for children because there are no endpoints of concern for residential dermal or inhalation toxicity that would affect adults . EPA has concluded the combined intermediate - term aggregated food, water, and residential exposures results in an aggregate MOE of 342 for children. Children’s aggregate MOE combines average food and water exposure from the chronic dietary exposure with residential exposure associated with contact wi th treated lawns ( hand - to - mouth + object to - mouth ). As the level of concern i s for MOEs that are lower than 3 00, these MOEs are not of concern.39

Table 13 . Intermediate - Term Aggregate Risk Calculations for 1 ,2 - Propanediol,3 - [3 - [1,3,3,3 - te tramethyl - 1 - [(trim ethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - Population PoD

mg/kg/day LOC 1 Max Allowable Exposure 2 mg/kg/day Average

Food & Water Exposure 3 mg/kg/day Residential

Exposure 4 mg/kg/day Aggregate

MOE (food and residential) 5 Child 25 3 00 0.08 0. 070624 0.002439 342 1 The LOC (Level of Concern) is based on the standard inter - , intra - species uncertainty factors and FQPA SF totaling 3 00. 2 Maximum Allowable Exposure (mg/kg/day) = PoD (Point of Departure)/LOC. 3 Average Food & Water Exposure = Chronic Dietary Exposure Table 5. 4 Residential Exposure = Child IT [HTM +OTM] 5 Aggregate MOE = [PoD/ (Avg Food & Water Exposure + Residential Exposure)]. VI. O CCUPATIONAL EXPOSURE/RISK PATHWAY

The Agency believes that establishing a tolerance exemption to include 40 CFR 180.920 will not significantly/measurably increase occupation exposure. Since there is no endpoint of concern selected for dermal or inhalation routes of exposure, a qualitative occupation exposure assessment was not c ompleted and occupational exposure is not of concern. VII. C UMULATIVE EXP OSURE

Cumulative effects from substances with a common mechanism of toxicity . Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity.” EPA has not found 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - to share a common mechanism of toxicity with any other substances, and that 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - does not appear to produce a to xic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that 1,2 - p ropanediol,3 - [3 - [1,3,3,3 - te t ramethyl 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - does not 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 EPA's website at http://www.epa.gov/pesticides/cumulative . VIII. E NVIRO NMENTAL JUSTICE STATEMENT

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, "Federal40

Actions to Address Environmental Justice in Minority Populations and Low - Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf . As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well - established procedures. In line with OPP policy, R D 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 a round the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under CSFII and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are an alyzed and categorized by subgroups based on age, season of the year, 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 risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post - application are evaluated . Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary pat terns among specific subgroups IX. E NVIRONMENTAL FATE CONSIDERATIONS

EPISuite 4.1 was run using the cluster of structurally related linear siloxanes Si - 2 to Si - 5 including the proposed inert ingredient, 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - (CAS Reg. No. 70280 - 68 - 1) . 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is expected to degrade in the atmosphere. The po tential for atmospheric oxidation (calculated 6 - 12 days) is consistent across the majority of the cluster and are considered as generally slow (>1 day to ≤ 10 days). However, the siloxanes with hydroxy functionality, Si - 4, CAS Reg. No. 70131 - 67 - 8 and the p roposed Si - 3 inert ingredient , CAS Reg. No. 70280 - 68 - 1, will degrade more rapid ly in the atmosphere; within less than 2 days. 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - will adsorb to soil and should not m igrate to water. Adsorption to soil ranges from low to moderate for the Si - 2 to Si - 3 siloxanes which have lower Log Kow values, whereas the higher Log Kow Si - 4 and Si - 5 siloxanes will adsorb strongly to soil. The cluster and proposed inert ingredient silo xanes should degrade and not persist in the environment. The potential for rapid biodegradation is reported for ultimate (weeks to months) and primary biodegradation (days to weeks). Values > 0.5 indicate that the chemical substances are likely to biodegra de. Overall, all of the compounds in the proposed siloxane cluster are likely to degrade to a primary metabolite and to mineralize (ultimate) to CO 2 and H 2 O. Henry’s Law (Bond Method) estimations indicate that the Si - 2 to Si - 5 alkyl substituted siloxanes in the cluster with high vapor pressures may be volatile from bodies of water. However, the siloxanes with hydroxyl functionality, Si - 4 CAS Reg. No. 70131 - 67 - 8 and the41

proposed Si - 3 inert CAS Reg. No. 70280 - 68 - 1, would be considered to be non - volatile from bodies of water based on their low vapor pressures. Ultimate (mineralization) fugacity estimations indicate a propensity for air, water and soil compartments that is directly proportional to increasing vapor pressure and also contingent on increasing Log Kow. For example, the Si - 2 CAS Reg. No. 107 - 46 - 0 has the most propensity for the air compartment (43%) and the least propensity for the soil compartment (11.2 %). In contrast, the Si - 5 CAS Reg. N o. 141 - 63 - 9 has a much lower propensity for air (7.5%) with much higher affinity for water (36.9%) and soil (53.9%). Moreover, the siloxanes with hydroxyl functionality, Si - 4 CAS Reg. No. 70131 - 67 - 8 and the proposed Si - 3 inert CAS Reg. No. 70280 - 68 - 1 both of which have lower vapor pressures than the other siloxanes within the cluster, have the least affinity for the air and water compartments and the most affinities for soil 53.95 and 79.4 respectively. X. E COTOXICITY Ecotoxicity estimations for CAS Reg. No. 70280 - 68 - 1 were obtained utilizing EPA ECOSAR 1.1 model. The SAR based on Neutral Organics provided very conservative estimation of aquatic toxicity. Other than the earthworm estimations, the EPA model ECOSAR has i ndicated that CAS Reg. No. 70280 - 68 - 1 may potentially be toxic to aquatic organisms. ECOSAR estimations were based on the theoretical (EPISuite 4.1) and Log Kow = 5.706, water solubility estimations of 0.03245 mg/L. The ECOSAR modeled results for CAS Reg. No. 70280 - 68 - 1 are consistent with the trends and analysis for the proposed siloxane cluster data that is reported from publically available sources and ECOSAR 1.1. Table 1 4 . Summary of Aquatic Ecological Toxicity ECOSAR Results for 1,2 - Propanediol,3 - [3 - [ 1,3,3,3 - te t ramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - ECOSAR Class Organism Duration Endpoint mg/L (ppm) Neutral Organics Fish 96 - hr LC50 0.137* Neutral Organics Daphnia 48 - hr LC50 0.109* Neutral Organics Green Algae 96 - hr EC50 0.336* Neutral Organics Fish Chronic 0.020 Neutral Organics Daphnia Chronic 0.028 Neutral Organics Green Algae Chronic 0.188* Neutral Organics Fish (SW) 96 - hr LC50 0.176* Neutral Organics Mysid 96 - hr LC50 0.011 Neutral Organics Fish (SW) Chronic 0.184* Neutral Organics Mysid (SW) Chronic 0.000307 Neutral Organics Earthworm 14 - day LC50 254.539 XI. R ISK CHARACTERIZATION

In March 2014, Exponent (1150 Connecticut Ave., NW Washington, DC 20036) on behalf of ISK Biosciences (7470 Auburn Road, Suite A, Concord, OH 44077) submitted a petition to the EPA to amend 40 CFR 180.920 by establishing an exemption from the requirement o f a tolerance for the use of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 -42

[(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - (CAS Reg. No. 70280 - 68 - 1) as an inert ingredient (antifoaming agent) in pesticide formulations applied to growing crops in accordance wit h 40 CFR 180.920 with a limitation of 10% in formulation. There is currently limited data available for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - to support the proposed use as a food use pesticide inert ing redient under 40 CFR 180.920, however data are available for a suitable cluster of structurally - related linear short chain siloxane compounds. The cluster analysis and resultant bridging/read - across analysis include an evaluation of the available studies a nd modeled data to address the physicochemical properties, mammalian metabolism, mammalian toxicity and environmental fate, of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - . An acute dietary risk assessment wa s not conducted because no endpoint of concern following a single exposure was identified in the available studies. A chronic dietary exposure assessment was completed and performed using the Dietary Exposure Evaluation Model DEEM FCID TM , Version 3.16. Th e chron ic Reference Dose (cRfD) of 0.08 mg/kg/day was determined on the basis of the 28 - day oral toxicity studies in rats. The LOAEL of 250 mg/kg/day was based on protoporp hyrin accumulation in the liver . This study provided the lowest NOAEL in the databa se (most sensitive endpoint) and will also provide the most protective limits for human effects. An UF of 100X (10 - fold for interspecies extrapolation and 10 - fold for intra species variability) and an FQPA safety factor of 3X (for subchronic to chronic study extrapolation) was applied to the NOAEL of 25 mg/kg/day to derive the cRfD. Therefore, the chronic populati on adjusted dose (cPAD) is 0.08 mg/kg/day. Based on analyses of estimated dietary risks for the general U.S. population and vari ous population subgroups, the chronic dietary exposure estimates resulting from the use of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - as an inert ingredient in pesticide formulations applied to growing crops a t a maximum concentration of 5% in the pesticide formulation are below the Agency’s level of concern. The chronic dietary exposure estimate for the highest exposed population subgroup , children 1 - 2 years old is 88.3 % of the chronic populati on adjusted dos e (cPAD) and 23.7 % of the cPAD for the general population. The Agency has not identified any concerns for carcinogenicity relating to 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - ; therefore, a cancer dietary exp osure assessment was not performed and an aggregate cancer risk is not a concern. Short - term aggregate exposure takes into account short - term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - may be used as an inert ingredient in pesticide products that could result in short - term residential exposure. However t he Agency has determined that it is only appropria te to aggregate chronic exposure through food and water with short - term residential exposures for children because there are no endpoints of concern for residential dermal or inhalation toxicity that would affect adults . EPA has concluded the combined shor t - term aggregated food, water, and residential exposures43

results in an aggregate MOE of 334 for children. As the level of concern i s for MOEs that are lower than 3 00, these MOEs are not of concern. Intermediate - term aggregate exposure takes into account intermediate - term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - may be used as an inert ingredient in pesticide products that could result in intermediate - term residential exposure. However t he Agency has determined that it is only appropriate to aggregate chronic exposure t hrough food and water with intermediate - term residential exposures for children because there are no endpoints of concern for residential dermal or inhalation toxicity that would affect adults . EPA has concluded the combined intermediate - term aggregated food, water, and residential exposures results in an aggregate MOE of 342 for children. As the level of concern i s for MOEs that are lower than 3 00, these MOEs are not of concern. Since there is no endpoint of concern selected for dermal or inhalation routes of exposure, a qualitative occupational exposure assessment was not completed for the proposed use of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - as a pesticide inert ingredient and occupational exposure is not of concern. 1,2 - Propanediol,3 - [3 - [1,3, 3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - is not volatile and has a moderately high Log Kow of 5.71 and low to negligible water solubility (0.03245 mg/L). 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl ]propoxy] - is not expected to be volatilized from bodies of water based on a Henrys Law Constant of 2.03 x - 8 atm - m 3 /mole. Atmospheric oxidation is expected to be 3.676 hours half - life with indicates moderate capability to be broken down in air. Based on th e Log Koc of 1.976, 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - will have low sorption to soil and sediment which may result in migration into ground water. The BCF of 2701 L/Lg wet - wt or Log BCF of 3.432 indic ates a moderate potential to bioaccumulate. Biodegradation is expected to occur rapidly. Ecotoxicity estimations for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - were obtained utilizing EPA ECOSAR 1.1 model. The SAR based on Neutral Organics provided very conservative estimation of aquatic toxicity. Other than the earthworm estimations, the EPA model ECOSAR has indicated that the proposed inert ingredient may potentially be toxic to aquatic organisms. The ECO SAR modeled results for 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - are consistent with the trends and analysis for the siloxane cluster data that is reported from publically available sources and ECOSAR 1.1. 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. Taking into consideration all available information on 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - , EPA concludes that there is a44

reasonable certainty that no harm to any population subgroup will result from aggregate exposure to 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl]propoxy] - when considering residential, , dietary exposure and all other n onoccupational sources of pesticide exposure for which there is reliable information. Therefore, the establishment of an exemption from tolerance under 40 CFR 180.920 for residues of 1,2 - propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disi loxanyl]propoxy] - (CAS Reg. No. 70280 - 68 - 1 ) when used as a pesticide inert ingredient (antifroaming agent) in pesticide formulations applied to growing crops with a limitation of 5 % in formulation, can be considered assessed as safe under section 408(q) of the FFDCA.45

REFERENCES Boorman GA , Chapin RE , Mitsumori K . (1990) . Testis and Epididymis . In: Boorman GA , Eustis SL , Elwell MR , Montgomery CA , MacKenzie WF , Eds. Pathology of the Fischer Rat: Reference and Atlas . San Diego: Academic Press , pp . 405

– 18 . MRID 49333 601 Thornber - Barwick A, Freeman E (2014). OECD QSAR Toolbox version 3.1 Evaluation of Poly(dimethylsiloxane) hydroxyl terminated (CAS Reg. No. 70131 - 67 - 8). Unpublished Project No. WD00 867.000 - 998. Exponent International Ltd. February 27, 2014. MRID 49333602 Exponent, Inc. (2014). Mammalian Metabolism and Excretion for CAS RN 70280 - 68 - 1. Unpublished Project No. ISK Metabolism - 201402. Exponent, Inc. February 27, 2014. MRID 49333603 Nagaike M (2013a). X - 22 - 1927: Acute Oral Toxi city Study in Female Rats (Fixed Dose Procedure). Unpublished Study Number: AN - 3329. Central Research Institute. Shiga, Japan. January 9, 2013. MRID 49333604 Nagaike M (2013b). X - 22 - 1927: Acute Dermal Toxicity Study in Male and Female Rats. Unpublished St udy Number: AN - 3330. Central Research Institute. Shiga, Japan. January 9, 2013. MRID 49333605 Miyamoto M (2013). X - 22 - 1927: Preliminary Reverse Mutation Test in Bacteria. Acute Oral Toxicity Study in Female Rats (Fixed Dose Procedure). Unpublished Study N umber: AN - 3355. Central Research Institute. Shiga, Japan. January 9, 2013. MRID 49333606 Exponent, Inc. (2014). Review of the Toxicological Data for the Short Chain Linear Siloxane Cluster in Support of the Reference Dose for the Proposed Inert Ingredien t, 1,2 - Propanediol, 3 - [3 - [1,3,3,3 - Tetramethyl - 1 - [(Trimethylsilyl)oxy] - 1 - Disiloxanyl]Propoxy] (CAS 70280 - 68 - 1), According to 40 CFR 180.920 Preharvest Applications. Unpublished Project No. ISK 201401 - A . Exponent, Inc. February 27, 2014. MRID 49333607 Exp onent, Inc. (2014). Compilation of References for Review of the Toxicology Data for the Proposed Inert Ingredient 1,2 - Propanediol, 3 - [3 - [1,3,3,3 - Tetramethyl - 1 - [(Trimethylsilyl)oxy] - 1 - Disiloxanyl]Propoxy] (CAS 70280 - 68 - 1). Unpublished Project No. ISK 2014 01 - B . Exponent, Inc. February 27, 2014. MRID 49333607 Attachment 1. EPA (1994) Toxicity Studies on TX - 135A (Hexamethyldisiloxane). Acute Oral Toxicity. MRID 49333607 Attachment 2. EPA (1966) Toxicity Studies on TX - 135A (Hexamethyldisiloxane). Acute Dermal. MRID 49333607 Attachment 3. Environment Canada, Health Canada (2011) Draft Screening Assessment for the Challenge. Trisiloxane, octamethyl - (Octamethyltrisiloxane). MRID 49333607 Attachment 4. EPA (1994) Acute Skin Irritation Study of Hexamethyld isiloxane in Albino Rabbits with Cover Letter dated 04/20/94. Report No.: 8EHQ - 86940001784. Stock No.: OTS057229646

MRID 49333607 Attachment 5. EPA (1966) Toxicity Studies on TX - 135A (Hexamethyldisiloxane). Eye Irritation Test. Document Control No.: 8694000 1705. Microfiche No.: OTS0557986. MRID 49333607 Attachment 6. OECD (2011) SIDS Initial Assessment Profile CAS No. 1873 - 88 - 7 1,1,1,3,5,5,5 - Heptamethyltrisiloxane (HMTS). MRID 49333607 Attachment 7. Dow Corning (2011) Material Safety Data Sheet for Dow Cor ning ® OS - 30. Version 1.9. Revision Date September 2, 2011. MRID 49333607 Attachment 8. EPA (1994) Report to Dow Corning Corporation Irritation Studies on Seven Samples (TX - 46A, TX - 46B, TX - 46C, TX - 46D, TX - 46E, TX - 47A, TX - 47B) with Cover Letter Dated 04209 4. MRID 49333607 Attachment 9. EPA (1994) MSDS for G.E. Silicone Rubber Sealant RTV108. Document Description: 8EHQ - 94 - 13120. MRID 49333607 Attachment 10. Cosmetic Ingredient Review (2010). Pink Book 1. Dimethiconal CIR Expert Panel Meeting. August 30, 2010. MRID 49333607 Attachment 11. ECHA (2014) Dodecamethylpentasiloxane Registered Data Dossier. Exp Key Acute toxicity: dermal. 001. MRID 49333607 Attachment 12. EPA (1994) Skin Contact Irritation Tests with DC200 FLUID/2 CS. With Cover Letter Dated 4/20/94. MRID 49333607 Attachment 13. EPA (1995) Sub - Acute Oral Toxicity Study on LS - 7130 in Rats. Document Description: 8EHQ - 0695 - 13475. MRID 49333607 Attachment 14. EPA (2011) Supplemental TSCA Section 8(e) Notificat ion (8EHQ - 0510 - 17952): Final Report - 28 - Day Oral (Gavage) Toxicity Study in the Sprague - Dawley Rat with Octamethyltrisiloxane (L - 3). Document Description: 8EHQ - 10 - 17951. Document Control No.: 8910000096. MRID 49333607 Attachment 15. EPA (2012) Supplemental TSCA 8(e) Notification (8EHQ - 09 - 17614): Final Report - Combined Repeated Dose Toxicity Study Submission Dated April 20, 2010. Document Description: 8EHQ - 09 - 17614. Document Control No.: 89120000464. MRID 49333607 Attachment 16 EPA (2009) Decam ethyltetrasiloxane (L4): 28 - Day Oral (Gavage) Toxicity Study in the Sprague - Dawley at with Decamethyltetrasiloxane. Document Description: 8EHQ - 09 - 1763 IB. Document Control No. 890900000393. MRID 49333607 Attachment 17. ECHA (2014) Decamethyltetrasiloxane Registered Data Dossier. Exp Key Repeated dose toxicity: oral. 001.47

MRID 49333607 Attachment 18. EPA (1994) Chronic (8 - Month) Feeding Studies with Methyl Siloxanes in Rabbits with Cover Letter Dated 42094. Document Control No. 86940001063. Microfiche No. OTS0556517. MRID 49333607 Attachment 19. EPA (1994) Chronic (One - Year) Feeding Studies with Methyl Siloxanes in Rats with Cover Letter Dated 42094. Document Control No. 86940001093. Microfiche No. OTS0556547. MRID 49333607 Attachment 20. EPA (1994) Repo rt to Dow Corning Corporation Ninety - Day Subacute Oral Toxicity of Pan Shield - Beagle Dogs, with Cover Letter Dated 042094. Document Control No. 86940001123. Microfiche No: OTS0556577. MRID 49333607 Attachment 21. EPA (1994) Chronic (One - Year) Feeding Stu dies with Dow Corning Special Polysiloxane in Rats with Cover Letter Dated 042094. Document Control No. 86940001086. MRID 49333607 Attachment 22. EPA (2009) 28 - Day Oral (Gavage) Toxicity Study in the Sprague - Dawley Rat with Dodecamethylpentasiloxane Docum ent Description: 8EHQ - 09 - 17683. Document Control No. 88100000012. MRID 49333607 Attachment 23. ECHA (2014) Dodecamethylpentasiloxane Registered Data Dossier. Exp Key Repeated dose toxicity: oral. 001. MRID 49333607 Attachment 24. OECD (2014) SIDS Initial Assessment Profile CAS No. 107 - 46 - 0 Hexamethyltrisiloxane (HMDS). MRID 49333607 Attachment 25. ECHA (2014) Hexamethyldisiloxane Registered Data Dossier. Exp Key Repeated dose toxicity: dermal. 001. MRID 49333607 Attachment 26. Cassidy S.L., Dotti A., Ko lesar G.B., Dochterman L.W., Meeks R.G., Chevalier H.J. (2001) Hexamethyldisiloxane: A 13 - Week Subchronic Whole - Body Inhalation Toxicity Study in Fischer 344 Rats. International Journal of Toxicology. MRID 49333607 Attachment 27. ECHA (2014) Hexamethyldis iloxane Registered Data Dossier. Exp Key Carcinogenicity.00l. MRID 49333607 Attachment 28. ECHA (2014) Octamethyltrisiloxane Registered Data Dossier. Exp Key Repeated dose toxicity: inhalation.00l. MRID 49333607 Attachment 29. ECHA (2014) Decamethyltetra siloxane Registered Data Dossier. Exp Key Repeated dose toxicity: inhalation.003. MRID 49333607 Attachment 30. ECHA (2014) Decamethyltetrasiloxane Registered Data Dossier. Exp Key Repeated dose toxicity: inhalation.00l.48

MRID 49333607 Attachment 31. EPA (2006) An Inhalation Two - Generation Reproductive Toxicity Study of Hexamethyldisiloxane (HMDS) in Rats, Including Developmental Neurotoxicity Assessment of the F2 Generation. MRID 49333607 Attachment 32. ECHA (2014) Octame thyltrisiloxane Registered Data Dossier. Exp Key Toxicity to reproduction: other studies .001. MRID 49333607 Attachment 33. ECHA (2014) Decamethyltetrasiloxane Registered Data Dossier. Exp Key Genetic toxicity in vitro.OOl and .002. MRID 49333607 Attachm ent 34. DEREK Report for CAS RN 70280 - 68 - 149

APPENDIX US EPA Ver. 3.16, 03 - 08 - d DEEM - FCID Chronic analysis for 1,2 - PROPANEDIOL,3 - [3 - [1,3,3,3 - TERTRAMETHYL - 1 - [(TRIMETHYLSILYL)OXY] - 1 - DISILOXANYL]PROPO XY] - 5% LIMITATION 3X SF NHANES 2003 - 2008 2 - day Residue file name: C: \ Users \ dlieu \ Documents \ EPA RD Pesticides \ Inerts \ 1,2 - Propanediol,3 - [3 - [1,3,3,3 - tetramethyl - 1 - [(trimethylsilyl)oxy] - 1 - disiloxanyl] propoxy] \ 2014 Assessment 180.920 \ DEEM Residue File for IN - 10699 Limit 5% 3X SF.R08 Adjustment factor #2 used. Analysis Date 01 - 13 - 2016/08:28:40 Residue file dated: 01 - 13 - 2016/08:28:14 Reference dose (RfD, Chronic) = .08 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 0.018934 23.7% Hispanic 0.020676 25.8% Non - Hisp - White 0.018580 23.2% Non - Hisp - Black 0.017595 22.0% Non - Hisp - Other 0.022336 27.9% Nursing Infants 0.024820 31.0% Non - Nursing Infants 0.045973 57.5% Female 13+ PREG 0.016524 20.7% Children 1 - 6 0.054667 68.3% Children 7 - 12 0.022741 28.4% Male 13 - 19 0.013376 16.7% Female 13 - 19/NP 0.013593 17.0% Male 20+ 0.014100 17.6% Female 20+/NP 0.015316 19.1% Seniors 55+ 0.015269 19.1% All Infants 0.039443 49.3% Female 13 - 50 0.014640 18.3% Children 1 - 2 0. 070624 88.3% Children 3 - 5 0.048563 60.7% Children 6 - 12 0.025055 31.3% Youth 13 - 19 0.013480 16.8% Adults 20 - 49 0.014474 18.1% Adults 50 - 99 0.015179 19.0% Female 13 - 49 0.014633 18.3%

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