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. Cancer 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

REFERENCES ............................................................................................................................. 45

APPENDIX................................................................................................................................... 49
3

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 from 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 an inert 

ingredient (antifoaming agent) in pesticide formulations applied to growing 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 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 and 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]-. 

1,2-Propanediol,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-across analysis of the 

linear short chain siloxane cluster, 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-1-

[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]- is 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. LOAELs for these studies were primarily based 

on adverse liver effects.

Dermal repeated dose toxicity studies are available for two of the structurally similar 

cluster 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 repeated dose toxicity studies are available for three of the structurally similar 

cluster compounds. Both a 28-day and 90-day rat inhalation study are available as well as a 1-

year chronic inhalation study in rats. The lowest inhalation NOAEC was 3.9 mg/L (equivalent to 

1000 mg/kg/day) in a 90-day study which is at limit 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. Because 
4

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 dietary 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 (structureactivity 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-tetramethyl-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 treatmentrelated. Renal tubular adenomas and carcinomas were also observed in the study but are 

attributable to male rat specific alpha-2μ-globulin mediated nephrotoxicity and therefore not 

relevant to cancer risk concerns in humans. Based on genotoxicity 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-propanediol,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 available studies.

No neurotoxicity 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 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-tetramethyl-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 metabolic 

pathways involved in the degradation of 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-1-

[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]- is a combination of ether hydrolysis followed by ßoxidation 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 polar carboxylic acid metabolites that could be 

readily conjugated and excreted.

An acute dietary risk assessment was 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 DEEMFCIDTM, Version 3.16. The chronic Reference Dose (cRfD) of 0.08 mg/kg/day was determined 
5

on the basis of the 28-day oral toxicity studies in rats in which the NOAEL was 25 mg/kg/day

and the LOAEL was 250 mg/kg/day based on protoporphyrin 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 species 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 population-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 pesticide 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 the 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 is for MOEs that are 

lower than 300, 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 the Agency has determined that it is only appropriate to aggregate 

chronic exposure through 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 is for MOEs that are lower than 300, 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.
6

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-m3/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-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 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 environmental justice concerns, to the extent possible, were considered 

in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal 

Actions to Address Environmental Justice in Minority Populations and Low-Income 

Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf.

Taking into consideration all available information on 1,2-propanediol,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-propanediol,3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-

disiloxanyl]propoxy]- when considering residential, , dietary 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-propanediol,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 formulation, 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 tolerance exemption for 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-

disiloxanyl]propoxy]- (CAS Reg. No. 70280-68-1) as a pesticide inert ingredient (antifoaming 

agent) under 40 CFR 180.920 (application 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 inert 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-across 

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 compounds and whether the 

data could be bridged was brought to members of the Office of Pollution Prevention and Toxics

(OPPT), Structure 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 structural 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 C13H34O5Si3 354.67

Proposed Siloxane Cluster for Read-Across

107-46-0 Si-2 C6H18OSi2 162.38

107-51-7 Si-3 C8H24O2Si3 236.54

1873-88-7 Si-3 C7H22O2Si3 221.50

141-62-8 Si-4 C10H30O3Si4 310.29

70131-67-8 Si-4 C8H26O5Si4 314.64

141-63-9 Si-5 C12H36O4Si5 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-

tetrramethyl-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. Overall it can be concluded 

that the proposed cluster of siloxane molecules exhibits the expected physicochemical 

trends for increasing/decreasing vapor pressure and log Kow that are directly affect by 

silicon chain length and the increased addition of alkyl silicon substituents or OH groups. 
Table 2. Physical and Chemical Properties of 1,2-propanediol,3-[3-[1,3,3,3-tetrramethyl-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 

m3/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 2.03E008

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 3.04E001

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 4.18E001

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 3.03E001

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 5.74E001

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 3.00E008

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 7.89E001

Air: 7.51/143

Water: 36.9/900

Soil: 

53.95/1.8e+003

Sediment: 

1.711/8.1e+003
III. HUMAN HEALTH ASSESSMENT

A. Summary of Data 

The 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 of 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 mammalian 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 oral toxicity study (MRID 49333603) in female rats the LD50 > 2000 mg/kg. 

No mortality was observed. Clinical signs included lowered locomotor activity, prone 

position 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 female rats the LD50 > 

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 siloxane clusters 

compounds were provided. CAS Reg. No. 107-51-7 had the lowest LC50 value (>22.6 

mg/L) for acute inhalation. Based on this LC50 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-tetrramethyl1-[(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 these 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 acute 
11

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 

these conclusions, 1,2-propanediol,3-[3-[1,3,3,3-tetrramethyl-1-[(trimethylsilyl)oxy]-1-

disiloxanyl]propoxy]- 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 LD50

Acute 

Dermal 

LD50

Acute 

Inhalation 

LC50

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 NonIrritating

NonIrritating Non-sensitizing

107-51-7 Si-3

> 2000 

mg/kg

> 2000 

mg/kg > 22.6 mg/L NonIrritating 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 NonIrritating

NonIrritating N/A

70131-

67-8

Si-4

> 5000 

mg/kg

> 2000 

mg/kg > 535 mg/L NonIrritating

NonIrritating Non-sensitizing

141-63-9 Si-5 N?A > 2000 

mg/kg N/A NonIrritating

NonIrritating 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 Table 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 and 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 of 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/day 
12

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 the spleen and 

the liver were increased in male of 640 mg/kg/day group. In necropsy, apparent spotty 

pattern of surface in the kidney in males of 160 mg/kg/day and higher groups, dark 

brownish change and enlargement in the liver and enlargement of the hepatic 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, total 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 eosinophilic 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 bodies 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) octamethyltrisiloxane 

(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 

consumption, 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 

proliferation and periportal chronic inflammation in males. After the 14-day recovery 

period, hepatocellular hypertrophy showed complete regression while brownish pigment 

accumulation 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 2011)

CAS Reg. No. 1873-88-7

In an oral combined repeated dose toxicity / reproductive developmental screening study 

(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: WIST(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 mortality, 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 weights of the liver in males, alpha 2μglobulin nephropathy effects in males, liver centrilobular hypertrophy in 3/5 females, 

minimal to slight diffuse thyroid follicular cell hypertrophy was observed in 2/5 females, 

and an increase in extramedullary hematopoiesis in females. The NOAEL was 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 

decamethyltetrasiloxane (CAS Reg. No. 141-62-8). The test material was administered 

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 accumulation 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 perilobular 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 the effect at 1000 mg/kg/day in 

the recovery group at the high dose level, the minimal effects 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 the presence of based on minimum protoporphyrin 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. 141-62-8) 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 was 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 weights in 2/4 males with slight testicular 

atrophy or hypoplasia in 1/4 males. The NOAEL in this study is 0.05%, estimated to be 
14

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-year chronic oral rat study with CAS Reg. No. 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 

0.05% 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 mean 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 unrelated 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 

recovery 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 

levels 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-tetramethyl-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 study (OECD Guideline 410), 

hexamethyldisiloxane (CAS Reg. No. 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 gains 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 weight ratio. No adverse changes in chemistry or

histopathology were observed in both males and females. The NOAEL for 

hexamethyldisiloxane in males was considered to be 500 mg/kg/day, based on reduced 

kidney and liver weights. There were no such effects 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 related to species-specific alpha 2μ-globulin mediated 

effects. Effects on liver weights were not accompanied 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 Reg. No.

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) exposed 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-tetramethyl-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 6 
16

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 in 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 1918 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 

males 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) 

exposure 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 the 

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. Histopathological 

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 droplet 

accumulation, protein casts and granular casts were noted 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 highest 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); the 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 Reg. No. 107-46-0 in rats, the 

test material was administered to Fischer 344 (F344) rats (20/sex/dose) at nominal 

(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, statistically significant 

effects upon body weight gain or food consumption, ophthalmoscopic changes, gross 
17

macroscopic necropsy findings, or organ weight changes were noted. However, when 

expressed as organ to body weight ratio, there was an increase in kidney and 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 2μ-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/m3 = (ppm value)(molecular

weight)/24.45, the molecular weight of CAS Reg. No. 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 the 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 slightly 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 wholebody inhalation in rats, CAS Reg. No. 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 severity 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 males 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 tumors (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 were 
18

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-2μ-globulin mediated nephrotoxicity. 

No evidence of neoplastic lesions was observed in females after 12 or 24 months. For this 

cluster analysis, 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 wholebody 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/day, 

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 Reg. No. 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 approximately 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-2μ-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 estimated 

using the formulation mg/m3 = (ppm value)(molecular weight)/24.45, where the 

molecular weight of CAS Reg. No. 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 

rats (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, organ 
19

weights, organ-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 Reg. 

No. 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 additional 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 neurobehavioral 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/m3- (ppm value)(molecular weight)/24.45, the 

molecular weight of CAS Reg. No. 141-62-8 is 310.69.

Table 6. Inhalation Repeated Dose Toxicity Profile of 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-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 Toxicity/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)

7.75(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 seen 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-2μ-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 inhalation 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. 2006) 

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 analysis 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-related short chain siloxane 

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 male rat specific alpha2μ-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), male 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 F0 and F1 parental animal received a complete detailed gross 

necropsy and selected organs were weighed. Daily observations included appearance, 

behavior, moribundity and mortality. For all Fl 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 included body weights and food 

consumption for females in the F0 and Fl generations. Litter examinations in Fl, F2 and F3

offspring included fetuses, sex, still births, runs, survival, litter viability and death. 

Additional behavioral endpoints (surface-righting, air-righting, reflexes, FOB, auditory 

startle response, locomotor activity and/or learning memory assessments) were conducted 

on F2 generation pups. Postmortem examinations of all surviving male and female 

parents after litter weaning and Fl and F2 pups (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 difficulties, 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 survival (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 small number of 5000 ppm group F0 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 

hyperplasia. These findings were not present in Fl females at any exposure level. Bile 

duct hyperplasia was only observed at the 5000 ppm exposure level for Fl males (24 of 

29) and females (12 of 28). The incidence was statistically significant. Periportal subacute inflammation was present in Fl 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 Fl 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 F2 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 Fl males and females at 1600 ppm. The NOAEC for offspring toxicity was 400 ppm 
22

(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 F2 females, and 

decreases in average and peak acoustic startle response on PND 20 in the 5000 ppm 

group F2 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 Reg. No.

107-46-0, Sprague-Dawley rats were exposed 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 F0 generation and 60 offspring/sex/group for Fl. 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 Fl generation was exposed from Lactation Day 5 (LD5) 

through the day prior to necropsy. No dosing between parturition and LD5. Pups not 

selected for the Fl generation were necropsied on postnatal day 21 and select organs were 

weighed. All F0 animals were subject to gross necropsy and select organs were weighed. 

Spermatogenic evaluations were performed on all F0 males. Designated tissues from all 

F0 parental animals in the control and 5000 ppm groups were examined microscopically.

There were no effects on mortality, clinical signs, spermatogenic endpoints, reproductive 

performance or parturition in the F0 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 F0 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 weights 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. Fl pups were not otherwise affected. 

The authors concluded that the test substance produced transient effects on body weight 

gain and food consumption in the F0 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. There were no test article-related effects on body weight, food consumption, FOB 
23

or motor activity parameters. Male rats exhibited hyaline droplet nephropathy at all 

concentrations tested, which was consistent with alpha-2μ-globulin mediated 

nephropathy. Both 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). Centrilobular 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. (ECHA 2014)

In an uterotrophic bioassay (OECD Guideline 440) was conducted on 

octamethyltrisiloxane (CAS Reg. No. 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 animals were treated subcutaneously with 17alpha-ethinyl estradiol (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 animals was given a combination of the estrogen receptor antagonist 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 effect 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 

test 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 

animals (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 were 
24

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 toxicity was reported as 50 mg/kg/day. The LOAEL for systemic toxicity was 

reported as 200 mg/kg/day based on liver and thyroid histopathology. The NOAEL for 

reproductive and developmental toxicity 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 Reg. No. 141-62-8) Sprague-Dawley rats

(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 examinations. 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 weight. 

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 treatment-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 reproductive 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 substance 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 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 available studies.
25

Neurotoxicity

No neurotoxicity 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 

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-tetramethyl-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 metabolic pathways involved in the degradation of 1,2-

propanediol,3-[3-[1,3,3,3-tetramethyl-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 polar carboxylic acid metabolites that could be readily 

conjugated and excreted.

Table 8. Toxicology Profile of 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-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;

Attachments 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 minimum 

protoporphyrin accumulation in males. 

MRID 49333607;

Attachment 16
26

Table 8. Toxicology Profile of 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-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 17

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

NOAEL = 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 3
27

Table 8. Toxicology Profile of 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-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 plasma 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 27
28

Table 8. Toxicology Profile of 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-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 33
29

Table 8. Toxicology Profile of 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-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 15
30

Table 8. Toxicology Profile of 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-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-neurobehavioral) = 10.6 mg/L

LAOEL (develop-neurobehavioral) = 33.1 mg/L 

based on lack of habituation in locomotor activity, 

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 and6

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 inflammation. A 90-day dog study had a 

NOAEL of 24 mg/kg/day with a LOAEL of 77 mg/kg/day based on increased relative 
31

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. 

Table 9. Summary of Toxicological 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 

UFA = 10 x

UFH = 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 

UFA = 10 x

UFH = 10 x

FQPA SF = 3 x

LOC for MOE = 

300

[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

UFA= 10 x

UFH= 10 x

FQPA SF = 3 x

LOC for MOE = 

300

[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 assessment 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.

UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members 

of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term 

study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA SF = 

Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = 

reference dose. MOE = margin of exposure. LOC = level of concern.

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 the 
32

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 

safety factor could be reduced to 3X 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. There 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 

assessment, 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 via 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 F2 females, and decreases in average and peak ascoustic startle response on 

PND 20 in the 5000 ppm group F2 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-propanediol,3-[3-[1,3,3,3-tetramethyl-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 level 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 safety factor can be reduced to 3X 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-propanediol,3-[3-[1,3,3,3-tetramethyl-1-

[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]- with 5% limitation in pesticide formulations. The 

petitioner requested the ability to use 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-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 methods of application and sites of 

application. 

A. Dietary Exposure:

 i. Acute exposure. No adverse effects attributable to a single exposure of 1,2-

propanediol,3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-

were seen in the toxicity databases. Therefore, acute dietary risk assessment for 1,2-

propanediol,3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]- is 

not required.

 ii. Chronic exposure. In conducting the chronic dietary exposure assessment using the 

Dietary Exposure Evaluation Model DEEM-FCIDTM, Version 3.16, EPA used food 

consumption information from the U.S. Department of Agriculture’s National Health and 

Nutrition Examination Survey, What we eat in America, (NHANES/WWEIA). This 

dietary survey was conducted from 2003 to 2008. As to residue levels in food, no residue 

data were submitted for 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-1-

[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-. 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 insecticides, 

herbicides, and fungicides. A complete description of the general approach taken to 

assess inert ingredient risks in the absence of residue data is contained in the 

memorandum entitled “Alkyl Amines 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 tolerance for a given commodity. Implicit 

in this assumption is that there would be similar rates of degradation (if any) between the 

active and inert ingredient and that the concentration of inert ingredient in the scenarios 

leading to these highest of tolerances would be no higher than the concentration of the 

active ingredient.
34

The Agency believes the assumptions used to estimate dietary exposures lead to an 

extremely conservative assessment of dietary risk due to a series of compounded 

conservatisms. First, assuming that the level of residue for an inert ingredient is equal to 

the level of residue for the active ingredient 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 with the highest 

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 at the highest tolerance level. In 

other words, EPA assumed 100 percent of all foods are treated with the inert ingredient at 

the rate and manner necessary to produce the highest residue legally possible 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 methodology to choose the 

highest possible residue that could be found on food and assumed that all food contained 

this residue. No consideration was given to potential degradation between harvest and 

consumption even though monitoring data shows that tolerance level residues are 

typically one to two orders of magnitude higher than actual residues in food when 

distributed in commerce. 

Accordingly, although sufficient information to quantify actual residue levels in food is 

not available, the compounding of these conservative assumptions will lead to a 

significant exaggeration of actual exposures. EPA does not believe that this approach 

underestimates exposure in the absence of residue data.

The additional adjustment factor 2 of 0.1 was utilized in this analysis to account for the 

5% limitation in formulation.

Table 10. Summary of Chronic Dietary Exposure and Risk of 1,2-Propanediol,3-[3-[1,3,3,3-tetramethyl-1-

[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-

Population Subgroup cPAD (mg/kg/day) Chronic

Exposure (mg/kg/day) %cPAD

General U.S. Population

0.08

0.018934 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-tetramethyl-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 exposed population subgroup, 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-tetramethyl-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-propanediol,3-[3-[1,3,3,3-

tetramethyl-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-propanediol,3-[3-[1,3,3,3-

tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-, a conservative drinking 

water concentration value of 100 parts per billion (ppb) based on screening level 

modeling was used to assess the contribution to drinking water for chronic dietary risk 

assessments for 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.html.

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

Oral absorption is assumed to be 100%. The 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 dose (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 the toxicological endpoint of 25

mg/kg/day identified from the 28-day oral toxicity study in rats based 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-tetramethyl-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 children 

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. 

Table 11. Residential Post-Application Short- and Intermediate-term Exposures and Risks for 1,2-

Propanediol,3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-

Pesticide 

Type

Exposure Scenario Application 

Rate1

Exposed Population & 

Exposure Duration2

Daily Dose 

(mg/kg/day)3

MOE4

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 is for MOEs that are 

lower than 300, these MOEs are not of 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 cPAD represent the highest safe exposures, 

taking into account all appropriate 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 probability of additional cancer cases given the estimated aggregate exposure. 

Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate 

food, water, and residential exposure to the POD to ensure that the MOE called for by the 

product of all applicable 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 assumptions 

discussed in Section IV for acute exposure. However there was no hazard attributable to a 

single exposure seen in the toxicity database for 1,2-propanediol,3-[3-[1,3,3,3-

tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-; therefore there is no concern 

for an acute 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 exposure assumptions 

discussed in Section IV from chronic exposure. The chronic analysis was based on a 28-

day oral toxicity study with a NOAEL of 25 mg/kg/day based on protoporphyrin 

accumulation in the liver. A chronic dietary risk assessment at the initially-proposed 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 from food and water 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 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-

propanediol,3-[3-[1,3,3,3-tetramethyl-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 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 the 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. 

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 is for MOEs that are lower 

than 300, these MOEs are not of concern.

Table 12. Short-Term Aggregate Risk Calculations for 1,2-Propanediol,3-[3-[1,3,3,3-tetramethyl-1-

[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-

Population

PoD

mg/kg/day LOC1

Max 

Allowable

Exposure2

mg/kg/day

Average

Food & 

Water

Exposure3

mg/kg/day

Residential 

Exposure4

mg/kg/day

Aggregate 

MOE

(food and

residential)5

Child 25 300 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 300.

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 Exposure)].

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-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 the Agency has determined 

that it is only appropriate to aggregate chronic exposure through 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 with treated lawns (hand-to-mouth + objectto-mouth). As the level of concern is for MOEs that are lower than 300, these MOEs are 

not of concern.
39

Table 13. Intermediate-Term Aggregate Risk Calculations for 1,2-Propanediol,3-[3-[1,3,3,3-tetramethyl-1-

[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-

Population

PoD

mg/kg/day LOC1

Max 

Allowable

Exposure2

mg/kg/day

Average

Food & 

Water

Exposure3

mg/kg/day

Residential 

Exposure4

mg/kg/day

Aggregate 

MOE

(food and

residential)5

Child 25 300 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 300.

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. OCCUPATIONAL 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 completed and occupational exposure is not of concern.

VII. CUMULATIVE EXPOSURE

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-propanediol,3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-

disiloxanyl]propoxy]- to share a common mechanism of toxicity with any other substances, and 

that 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-

does not appear to produce a toxic metabolite produced by other substances. For the purposes of 

this tolerance action, therefore, EPA has assumed that 1,2-propanediol,3-[3-[1,3,3,3-tetramethyl1-[(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. ENVIRONMENTAL 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, "Federal 
40

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, RD estimates risks 

to population subgroups from pesticide exposures that are based on patterns of that subgroup’s 

food and water consumption, and activities in and around the home that involve pesticide use in 

a residential setting. Extensive data on food consumption patterns are compiled by the USDA 

under CSFII and are used in pesticide risk assessments for all registered food uses of a pesticide. 

These data are analyzed 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 patterns among specific subgroups

IX. ENVIRONMENTAL 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 potential 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 

proposed Si-3 inert ingredient, CAS Reg. No. 70280-68-1, will degrade more rapidly 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 migrate 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 siloxanes 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 biodegrade. Overall, all of the compounds in the proposed siloxane cluster are likely 

to degrade to a primary metabolite and to mineralize (ultimate) to CO2 and H2O.

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 the 
41

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. No. 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. ECOTOXICITY

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 

indicated 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 14. Summary of Aquatic Ecological Toxicity ECOSAR Results for 1,2-Propanediol,3-[3-[1,3,3,3-

tetramethyl-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. RISK 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 of 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 with 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 ingredient 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 and 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 was 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 DEEMFCIDTM, Version 3.16. The chronic 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 protoporphyrin 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 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 populationadjusted 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 pesticide 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 chronic population adjusted dose (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 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 the 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 
43

results in an aggregate MOE of 334 for children. As the level of concern is for MOEs that are 

lower than 300, 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 the Agency has determined that it is only appropriate to aggregate 

chronic exposure through 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 is for MOEs that are lower than 300, 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-m3/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-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 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 environmental justice concerns, to the extent possible, were considered 

in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal 

Actions to Address Environmental Justice in Minority Populations and Low-Income 

Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf.

Taking into consideration all available information on 1,2-propanediol,3-[3-[1,3,3,3-

tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]-, EPA concludes that there is a 
44

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 

nonoccupational 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-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% in formulation, can be 

considered assessed as safe under section 408(q) of the FFDCA.
45

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Linear Siloxane Cluster in Support of the Reference Dose 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), According to 40 CFR 180.920 Preharvest Applications. Unpublished Project No. ISK201401-A. Exponent, Inc. February 27, 2014.

MRID 49333607 Exponent, 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. ISK201401-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 Hexamethyldisiloxane 

in Albino Rabbits with Cover Letter dated 04/20/94. Report No.: 8EHQ-86940001784. Stock No.: 

OTS0572296
46

MRID 49333607 Attachment 5. EPA (1966) Toxicity Studies on TX-135A 

(Hexamethyldisiloxane). Eye Irritation Test. Document Control No.: 86940001705. 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 Corning 

® 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 042094.

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) Notification 

(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) Decamethyltetrasiloxane (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) Report 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 Studies 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 Document 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., Kolesar 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) Hexamethyldisiloxane 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) Decamethyltetrasiloxane 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) Octamethyltrisiloxane 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 Attachment 34. DEREK Report for CAS RN 70280-68-1
49

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]PROPOXY]- 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%

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