Registration Dossier

Administrative data

Description of key information

No data are available for [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane.

The read-across substance [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane was found to be a skin sensitiser in a study conducted according to OECD 429 and in compliance with GLP.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Data are read across from an LLNA study from [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane (2897-60-1) which was conducted according to OECD 429 and in compliance with GLP. Test substance was applied to the ears of 4 mice per group at concentrations of 0, 25%, 50% and 100%. A stimulation index of >3 was recorded for the two higher concentrations of test material (50% v/v and 100%), relative to the negative controls. It was concluded that the test substance was a skin sensitiser based on the results of this study. This study was selected to fulfil the data requirements for this endpoint as a conservative approach as the results indicated that substance is sensitising.

A second sensitisation study is available for the analogue substance [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (2530-83-8) from a Buehler study conducted according to OECD 406 and in compliance with GLP. No evidence of skin sensitisation was observed following induction and challenge with unchanged test substance applied to intact guinea pig skin. This result is included in the dataset for completeness but is not used to fill the data gap for the target substance as it indicates lack of sensitisation.

 

Read-across justification

There are no available measured data [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane (CAS 65779-47-5) for skin sensitisation. Therefore, the Annex requirements are fulfilled with data on structural analogous substances. This document describes the analogue approach for fulfilling this endpoint by read-across from the source substances, [3‑(2,3‑epoxypropoxy)propyl]diethoxy(methyl)silane, (2897-60-1), according to the Read-across Assessment Framework (RAAF)[1].

Read-across is proposed in accordance with RAAF Scenario 2: “This scenario covers the analogue approach for which the read-across hypothesis is based on different compounds which have the same type of effect(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst case.”

The read-across justification is presented (Table 5.6.4) according to RAAF scenario 2 assessment elements (AE) as outlined in Table B1 of the RAAF1:

Table 1: RAAF scenario 2 assessment elements (AE) as given in Appendix B (Table B1) of the RAAF1

AE A.1

Characterisation of source substance

AE A.2

Link of structural similarity and differences with the proposed Prediction

AE A.3

Reliability and adequacy of the source study

AE 2.1

Compounds the test organism is exposed to

AE 2.2

Common underlying mechanism, qualitative aspects

AE 2.3

Common underlying mechanism, quantitative aspects

AE 2.4

Exposure to other compounds than to those linked to the prediction

AE 2.5

Occurrence of other effects than covered by the hypothesis and Justification

AE A.4

Bias that influences the prediction

 

1.  AE A.1 Identity and characterisation of the source substance

The source substance [3‑(2,3‑epoxypropoxy)propyl]diethoxy(methyl)silane, (2897-60-1) is a diethoxysilane with methyl and 3-(2,3-epoxypropoxy)propyl side-chains. Its estimated hydrolysis half-lives at 20-25°C 0.4 hours at pH 4, 0.5 hours at pH 5, 11.7 hours pH 7 and 0.2 hours at pH 9. The calculated half-life at37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life will be less than 0.5 hours. The products of hydrolysis are [3-(2,3-epoxypropoxy)propyl]methylsilanediol (1 mole) and ethanol (2 moles).The source substance has log Kow of 2.7 at 20°C (estimated), predicted water solubility of 1200 and measured vapour pressure of 0.42 Pa at 25°C.

2.  AE A.2 Link of structural similarities and differences with the proposed prediction

The target substance, [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane (CAS 65779-47-5) is a dimethoxysilane with a methyl and a 3-(2,3-epoxypropoxy)propyl side-chains.

The first possible source substance, [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, (2530-83-8) is a trimethoxysilane with a 3-(2,3-epoxypropoxy)propyl side-chain.

The second possible source substance, [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane, (2897-60-1) is a diethoxysilane with a methyl and a 3-(2,3-epoxypropoxy)propyl side-chains.

The target and possible source substances are all alkoxysilanes with a 3-(2,3-epoxypropoxy)propyl side-chain. They have the general structural formula shown in Figure 1 (attached).

For the target substance:                           R1 is methyl,      R2 is methyl.

For the source substance 2530-83-8:          R1 is methoxy,   R2 is methyl.

For the source substance 2897-60-1:        R1 is methyl,      R2 is ethyl.

Therefore, all structural features of the target substance (3-(2,3-epoxypropoxy)propyl side-chain, dialkoxy(methyl)silane, methoxysilane) are present in one or both of the possible source substances.

The target substance and the source substance 2530-83-8 are both methoxysilanes with a 3-(2,3-epoxypropoxy)propyl side-chain. The difference between these substances is that one of the three methoxy groups in the source substance is replaced by a methyl group in the target substance.

The target substance and the source substance 2897-60-1 are both dialkoxysilanes with methyl and 3-(2,3-epoxypropoxy)propyl side-chains. The difference between these substances is that the two alkoxy groups are ethoxy for the source substance and methoxy for the target substance.

The three substances all have similar moderate molecular weight (220-248) and low vapour pressure (0.4-3 Pa at 25°C). They all have low log Kow (0.5-2.7) and moderate to high water solubility (1200 – 110000 mg/l), with the target substance being in between the two source substances. All the substances hydrolyse rapidly, with half-lives of <12 hours at pH 7 and 25°C and 5 s at pH 2 and 37.5°C.

Table 2: Physicochemical properties

Property

Target substance

Source substance

Source substance

CAS

65799-47-5

2530-83-8

2897-60-1

Type

Dimethoxy

Trimethoxy

Diethoxy

Name

[3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane

[3-(2,3-epoxypropoxy)propyl]trimethoxysilane

[3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane

Hydrolysis products

[3-(2,3-epoxypropoxy)propyl]methylsilanediol (1 mole) and methanol (2 moles)

[3-(2,3-epoxypropoxy)propyl]silanetriol (1 mole) and methanol (3 moles)

[3-(2,3-epoxypropoxy)propyl]methylsilanediol (1 mole) and ethanol (2 moles)

MW

220.34

236.34

248.4

WS / mg/l

1.2E+04

1.1E+05

1200

Log Kow

1.7

0.5

2.7

Hydrolysis half-life at pH 7 and 25°C

1.6 hours

6.5 hours (measured)

11.7 hours

Hydrolysis half-life at pH 7 and 37.5°C

0.6 hours

3.3 hours (measured)

4.4 hours

Hydrolysis half-life at pH 2 and 37.5°C

5 s

5 s

5 s

VP at 25°C / Pa

3.0

1.1

0.42 (measured)

HP MW

192.29

194.26

192.29

HP WS / mg/l

1E+06 (limited to around 1000 mg/l by condensation reactions)

1E+06 (limited to around 1000 mg/l by condensation reactions)

1E+06 (limited to around 1000 mg/l by condensation reactions)

HP Log Kow

-0.7

-2.6

-0.7

HP VP at 25°C / Pa

0.0011

1.7E-05

0.0011

 

3.  AE A.3 Reliability and adequacy of the source study

[3-(2,3-Epoxypropoxy)propyl]diethoxy(methyl)silane has been tested in a valid LLNA study conducted according to OECD 429 and in compliance with GLP. Test substance was applied to the ears of 4 mice per group at concentrations of 0, 25%, 50% and 100%. A stimulation index of >3 was recorded for the two higher concentrations of test material (50% v/v and 100%), relative to the negative controls. It was concluded that the test substance was a skin sensitiser based on the results of this study.

Data are available for [3-(2,3-epoxypropoxy)propyl]trimethoxysilane from a Buehler study conducted according to OECD 406 and in compliance with GLP. No evidence of skin sensitisation was observed following induction and challenge with unchanged test substance applied to intact guinea pig skin. This result is included for information in view of the positive result from an LLNA study on the diethoxy analogue.

4.  AE A.4 Bias that influences the prediction

Data on the source substance [3‑(2,3‑epoxypropoxy)propyl]diethoxy(methyl)silane were read across to the registered (target) substance [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane. The source substance and the target substance have similar chemical structure and physicochemical properties. The substances hydrolyse at comparable rates and produce similar silicon-containing hydrolysis products. The source substance gives a similar but not identical silanol hydrolysis product as the target substance, [3-(2,3-epoxypropoxy)propyl]silanetriol, and the same non-silanol hydrolysis product as the target substance, methanol. Most structural features of the target substance (3-(2,3-epoxypropoxy)propyl side-chain, dialkoxy(methyl)silane) are present in the source substance. Both substances show similar predicted toxicity profiles using the OECD QSAR Toolbox v. 4.1, and have the same structural alerts. Therefore, their toxicological properties are expected to be similar, with similar sensitisation. The source substance is one of the closest structural analogues to the target substance. Data are also available for the analogue substance 3‑(2,3‑epoxypropoxy)propyltrimethoxysilane, (2530-83-8). These data were not used to fill the data gap for the target substance as they indicate lack of sensitisation; the source substance [3‑(2,3‑epoxypropoxy)propyl]diethoxy(methyl)silane was selected as a conservative approach as the results indicated that substance is sensitising. However, data for [3‑(2,3‑epoxypropoxy)propyl]trimethoxysilane, (2530-83-8) are included in the dataset for completeness.

5.  AE A.2.1 Compounds the test organism is exposed to

The source substances as well as the target substance hydrolyse at similar rate in contact with water under conditions relevant for oral exposure. Therefore, the test organism could possibly be exposed to the parent substance and its hydrolysis products, [3-(2,3-epoxypropoxy)propyl]silanetriol and methanol. The source and target substances have been profiled using the OECD QSAR Toolbox v. 4.1. The substances and their silanol hydrolysis products show similar profiles for all toxicological endpoints. The potential source substances identified by the OECD QSAR Toolbox have varying results for skin sensitisation, therefore a worst-case approach is followed and the target substance is classified for skin sensitisation.

6.  AE A.2.2 and A.2.3 Common underlying mechanism, qualitative and quantitative aspects

No skin sensitisation data are available for the target substance [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane, therefore data are read across from the structurally analogous substances [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, (2530-83-8) and[3‑(2,3‑epoxypropoxy)propyl]diethoxy(methyl)silane, (2897-60-1). These three substances hydrolyse at comparable rates 1 moles of a [3-(2,3-epoxypropoxy)propyl silanol. The non-silanol hydrolysis products are methanol and ethanol, which are of known toxicity and not expected to contribute to the effects observed for this endpoint. Moreover, they have similar predicted physicochemical properties, and are predicted by QSAR Toolbox to be subject to similar metabolic processes. The source substances have conflicting results from skin sensitisation, so the more conservative result for [3‑(2,3‑epoxypropoxy)propyl]diethoxy(methyl)silane has been selected as key, and classification is based on the results of this study.

7.  AE 2.4 Exposure to other compounds than to those linked to the prediction

The registration substance, [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane has a purity greater than 98 %.

Neither the target substance nor the source substances have impurities of toxicological concern.

The purity of test substance in the study with the source substance, [3‑(2,3‑epoxypropoxy)propyl]diethoxy(methyl)silane, was not reported. However, the Substance Identity Profile for the REACH Registration of this substance indicates that it has a purity of >95% and no impurities are present at >1%.

8.  AE 2.5 Occurrence of Other Effects than Covered by the Hypothesis and Justification

Not relevant.


[1]European Chemicals Agency (ECHA) (2015) Read-across Assessment Framework. Appendix B, Scenario 2.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

On the basis of available read-across data, [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane is classified as a Skin Sensitiser Category 1B; ‘H317: may cause an allergic skin reaction’ in accordance with Regulation (EC) No. 1272/2008