Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): read-across from 1,1,1,3,5,5,5 -heptamethyl-3 -[(trimethylsilyl)oxy]trisiloxane;

negative result with and without metabolic activation in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 Escherichia coli WP2 from 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (similar to OECD TG 471) (Sarwar, G. (2001a)).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are no genotoxicity data available for the registered substance. However, reliable data are available for a structural analogue.

1,1,1,3,5,5,5 -Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane has been tested for mutagenicity to bacteria, in a study which was conducted according to a Japanese guideline similar to OECD TG 471, not in compliance with GLP (Sarwar, G. (2001a)). No evidence of a test substance related increase in the number of revertants was observed with or without metabolic activation in the initial or the repeat experiment, both of which used the pre-incubation method, in Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537, and E.coli WP2 uvrA. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Read-across justification

There are no available measured data for 1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane (CAS 3555-47-3) for genetic toxicity. This document describes the analogue approach for fulfilling this endpoint by read-across from a source substance 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (CAS 17928-28-8), according to the Read-across Assessment Framework (RAAF) .

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, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (CAS 17928-28-8), is a tertiary branched methylated siloxane structure of four Si atoms. The longest siloxane chain consists of three silicon atoms and two oxygen atoms, with a Si-O branch on the central silicon atom in the chain. The silicon atoms are fully substituted by methyl groups. Hydrolysis half-life values of 3.6 h at pH 4, 630 h at pH 7, 5.3 h at pH 9 and 20-25°C were obtained using an accepted calculation method.  

At pH 7 (relevant for genetic toxicity studies), he hydrolysis half-life is expected to be approximately 230 hours. The products of hydrolysis are trimethylsilanol (3 moles) and methylsilanetriol (1 moles).

The source substance has log Kow of 8.2 at 20°C (QSAR), water solubility of 0.00189 mg/l at 23°C (QSAR) and vapour pressure of 210 Pa at 25°C (OECD 104).

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

The registration substance, 1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane (CAS 3555-47-3), and the read-across substance, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (CAS 17928-28-8), are structurally similar and are members of an analogue group of linear and branched siloxanes.

1,1,1,3,5,5,5-Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (CAS 17928-28-8)  a is a tertiary branched methylated siloxane structure of four Si atoms, while 1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane (CAS 3555-47-3) is a quaternary branched methylated siloxane structure of five Si atoms. In both substances the longest siloxane chain consists of three silicon atoms and two oxygen atoms. The source substance has a Si-O branch on the central silicon atom in the chain, while the target substance has two oxygen atoms, with two Si-O branches on the central silicon atom in the chain. The silicon atoms are fully substituted by methyl groups.

The Si-containing hydrolysis product for both the target and source substance is trimethylsilanol. (Poly)silicic acid is the non-Si hydrolysis product for the target substance and methylsilanetriol for the source substance. These two substances both hydrolyse in similar rate to 4 moles or 3 moles of trimethylsilanol.

Table 2: Physico-chemical properties

Property

Target substance

Source substance

Substance name

1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane

1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane

CAS number

3555-47-3

17928-28-8

Hydrolysis half-life at pH 7 and 37.5°C

>200-2000 h

230 h

Silanol hydrolysis product

Trimethylsilanol and (poly)silicic acid

Trimethylsilanol andmethylsilanetriol

LogKow value

9 at 20°C (QSAR)

8.2 at 20°C (QSAR)

Vapour pressure

27.6 hPa at 20°C (OECD 104)

210 Pa at 25°C (OECD 104)

Water solubility

0.1507 µg/l at 20-25°C (measured)

0.00189 mg/l at 23°C (QSAR)

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

1,1,1,3,5,5,5-Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane has been tested for mutagenicity to bacteria, in a study which was conducted according to a Japanese guideline similar to OECD TG 471, not in compliance with GLP (Sarwar, G. (2001a)). No evidence of a test substance related increase in the number of revertants was observed with or without metabolic activation in the initial or the repeat experiment, both of which used the pre-incubation method, in Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537, and E.coli WP2 uvrA. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

4.       AE A.4 Bias that influences the prediction

Data on the source substance 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (CAS 17928-28-8) were read-across to the registered (target) substance 1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane (CAS 3555-47-3). The source substance and the target substance have similar chemical structure and physico-chemical properties. Both substances hydrolyse at similar rate to the same Si-containing hydrolysis product, trimethylsilanol. However, the non-silanol hydrolysis products are different, (poly)silicic acid and methylsilanetriol for the target and source substance, respectively. Despite that, their toxicological properties are expected to be similar, with similar acute toxicity. No other data for relevant substances were available. These substances are the closest structural analogues to the target substance; other siloxanes show consistent results (PFA, 2013aa).

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

Both substances hydrolyse at similar rates to the same Si-containing hydrolysis product. Therefore, the test organism is might be exposed to both the parent substances or the hydrolysis products.  The source and target substances have been profiled using the OECD QSAR Toolbox v. 4.1. The three substances and their silanol hydrolysis products show similar profiles for all toxicological endpoints. No alert for acute toxicity was detected by OECD QSAR Toolbox v.4.1.  

The genetic toxicity potential of (poly)silicic acid is well established. No classification for genetic toxicity has been assigned to the substance.

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

No toxicity data are available for the target substance 1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane (CAS 3555-47-3), therefore data are read-across from the structurally analogous substance 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (CAS 17928-28-8). These substances hydrolyse at similar rate to 4 moles or 3 moles of trimethylsilanol. The non-silanol hydrolysis products, (poly)silicic acid and methylsilanetriol, are not expected to be relevant for this endpoint. Moreover, they have similar physico-chemical properties. Thus, both substances are expected to have similar toxicity profiles.

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

The target substance, 1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane (CAS 3555-47-3), has a named impurity impurity at 5-20% is 1,1,1,5,5,5-Hexamethyl-3-[(trimethylsilyl)oxy]-3-trisiloxanyl tris(trimethylsilyl) orthosilicate (CAS 18602-90-9 and synonym of Q2M6 or M6Q2). No toxicological data are available for M6Q2 however based on the weight of evidence for linear and branched siloxanes acute toxicity is not expected (PFA, 2013u). The source substance, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (CAS 17928-28-8), does not have any impurities of toxicological concern.

The test substance in the study with the source substance, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (CAS 17928-28-8), has a purity of 99.9%.

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.

PFA (2013aa). Peter Fisk Associates, Genotox Analogue Report, PFA.300.004.001.

PFA (2013u). Peter Fisk Associates, Mammalian toxicity of linear and branched siloxanes Analogue Report, PFA.300.002.008

Justification for classification or non-classification

Based on the available read-across in vitro genotoxicity data, 1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane is not classified for mutagenicity according to Regulation (EC) No 1272/2008 .

Categories Display