Dichlorododecylmethylsilane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No measured data are available to assess the in vitro bacterial mutagenicity potential of the registered substance, however, reliable data are available for the structurally analogue substances trichloro(hexadecyl)silane (CAS 5894-60-0), triethoxyoctylsilane (CAS 2943-75-1), and dichloromethyloctylsilane (CAS 14799-93-0).

Bacterial Mutagenicity: RA to CAS 5894 -60 -0, CAS 2943 -75 -1, CAS 14799 -93 -0: negative

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

experiment I: at 1000 µg/plate (TA 100, TA 1535, TA 1537 without S9-mix; TA 1537 with S9-mix); experiment II: at 316 and 1000 µg/plate (all strains, without S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 316 and 1000 µg/plate (without S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

experiment I:at 1000 µg/plate (all strains, with and without S9-mix); experiment II: at 1000 µg/plate (all strains, without S9-mix); at 316 µg/plate (TA 98, TA 1535. TA 1537, without S9-mix), =316 µg/plate (all strains, with S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

experiment I: at 1000 µg/plate (with and without S9-mix); experiment II: =316 µg/plate (with and without S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: CAS 5894-60-0, LPT, 2002

Conclusions:

Interpretation of results: negative

Source substances trichloro(hexadecyl)silane (CAS 5894-60-0), triethoxyoctylsilane (CAS 2943-75-1) and dichloromethyloctylsilane (CAS 14799-93-0) have been tested in compliance with OECD 471, under GLP conditions. No increase in the number of revertant colonies compared with the solvent control was observed for the source substances in any of the Salmonella typhimurium strains TA98, TA 100, TA102, TA 1535 and TA 1537 and/or E. coli WP2 uvr A when tested with and without metabolic activation in either the initial plate incorporation or the repeat experiment. It is concluded that the source substances are negative for mutagenicity to bacteria under the conditions of the test. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in genetic toxicity potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for grouping of substances and read-across

There are only limited data available on genetic toxicity of dichlorododecylmethylsilane (CAS 18407-07-3). In order to fulfil the standard information requirements set out in Annex VII, 8.4., in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted. In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across). Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

 

Overview of genetic toxicity

CAS	Chemical name	Molecular weight [g/mol]	Gene mutation in vitro (Ames)
18407-07-3 (a)	Dichlorododecylmethylsilane	283.35	RA: CAS 5894 -60 -0  RA: CAS 2943-75-1  RA: CAS 14799-93-0
5894-60-0 (b)	Trichloro(hexadecyl)silane	359.88	Experimental result: negative
2943-75-1 (b)	Triethoxyoctylsilane	276.49	Experimental result: negative
14799-93-0 (b)	Dichloromethyloctylsilane	227.25	Experimental result: negative

(a) The substance subject to registration is indicated in bold font.

(b) Reference (read-across) substances are indicated in normal font.

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Dichlorododecylmethylsilane (CAS 18407-07-3).

Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

 

Discussion

No data on genetic toxicity (mutagenicity) in bacteria cells is available with Dichlorododecylmethylsilane (CAS 18407-07-3). Therefore, read across from the structurally analogue substances Trichloro(hexadecyl)silane (CAS 5894-60-0), Triethoxyoctylsilane (CAS 2943-75-1) and Dichloromethyloctylsilane (CAS 14799-93-0) was applied.

 

Genetic toxicity (mutagenicity) in bacteria in vitro

 

CAS 5894-60-0

A reliable bacterial gene mutation study (Ames test) performed according to OECD TG 471 and in compliance with GLP with Trichloro(hexadecyl)silane (CAS 5894-60-0) is available (LPT, 2002). The strains Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 were tested according to the plate incorporation (experiment I) and pre-incubation (experiment II) procedure in the absence and presence of a metabolic activation system (Aroclor-induced rat liver S9-mix). Two independent experiments were conducted in three repetitions at each concentration from 10 to 1000 µg/plate (experiment I and II). Cytotoxicity was recorded in the tester strains TA 100, TA 1535 and TA 1537 at the highest concentration of 1000 µg/plate (experiment I without metabolic activation) and for the tester strain TA 1537 at 1000 µg/plate (experiment I with metabolic activation). Moreover, cytotoxic effects were recorded at concentrations =316 µg/plate for all tester strains in the second experiment without metabolic activation. No precipitation was recorded in both experiments carried out with and without metabolic activation. Appropriate solvent (ethylene glycol dimethylether) and positive controls were included and gave the expected results. No significant increase in the number of revertants was observed in any of the tester strains with and without metabolic activation.

 

CAS 2943-75-1

Another reliable bacterial gene mutation study (Ames test) performed according to OECD TG 471 and in compliance with GLP with Triethoxyoctylsilane (CAS 2943-75-1) is available (MA BioServices, 1998). No evidence of a substance related increase in the number of revertants was observed at concentrations from 75 to 5000 µg/plate with or without activation in the tester strains TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvrA in two independent experiments in which the pre-incubation method was used. No toxicity to bacteria was observed up to limit concentrations. Appropriate solvent and positive 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.

 

CAS 14799-93-0

Another reliable bacterial gene mutation study (Ames test) performed according to OECD TG 471 and in compliance with GLP with dichloromethyloctylsilane (CAS 14799-93-0) is available (LPT, 2002). The strains Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 were tested according to the plate incorporation (experiment I) and pre-incubation (experiment II) procedure in the absence and presence of a metabolic activation system (Aroclor-induced rat liver S9-mix). Two independent experiments were conducted in three repetitions at each concentration from 10 to 1000 µg/plate (experiment I and II). Cytotoxicity was observed in all tester strains in the first experiment carried out with and without metabolic activation at the highest concentration of 1000 µg/plate. Moreover, cytotoxicity was recorded in all tester strains in the second experiment carried out without metabolic activation at the highest concentration of 1000 µg/plate and for TA 98, TA 102, TA 1535 and TA 1537 at a concentration of 316 µg/plate. Cytotoxicity was recorded for all tester strains in the second experiment (with metabolic activation) at concentrations of 316 and 1000 µg/plate. Precipitation was recorded at the highest concentration of 1000 µg/plate in the first experiment (with and without metabolic activation) and at 316 and 1000 µg/plate in the second experiment (with and without metabolic activation). Appropriate solvent (ethylene glycol dimethylether) and positive controls were included and gave the expected results. No significant increase in the number of revertants was observed in any of the tester strains with and without metabolic activation. Based on the results the test material was considered to be not mutagenic to bacteria under the conditions of the tests.

 

Taking into consideration the above results generated from the structurally analogue substances the target substance Dichlorododecylmethylsilane (CAS 18407-07-3) is not expected to be mutagenic to bacteria. 

Justification for classification or non-classification

Based on the available data on genetic toxicity of the structurally analogue substances the registered substance is not considered to induce genetic toxicity in bacteria. However, no final decision on classification for genetic toxicity according to Regulation (EC) 1272/2008 can be made, as no information on chromosomal aberration and mutagenicity in mammalian cells/in vivo is available.