Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA98, TA100, TA 102, TA1535 and TA1537 (OECD TG 471) (Donath, C., 2012).
Cytogenicity in mammalian cells: positive in Chinese hamster V79 cells with metabolic activation in repeat assay only (OECD TG 473) (Zeller, J., 2013).
Mutagenicity in mammalian cells: not required as a positive result was obtained from the in vitro cytogenicity assay.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available (further information necessary)

Additional information

Data are available from reliable in vitro studies on 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane for mutagenicity to bacterial and mammalian cells, and for cytogenicity to mammalian cells.

2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane has been tested in a reliable bacterial mutagenicity study conducted according to OECD TG 471 and in compliance with GLP (Donath, C., 2012). No test-substance related increase in the number of revertants was observed when Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 were exposed with and without metabolic activation up to limit concentrations. 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.

2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane has been tested according to OECD 474 and in compliance with GLP, using Chinese hamster V79 cells (Zeller, J., 2013). No evidence for induction of numerical chromosome aberrations was observed in either the initial or the repeat assay. Without metabolic activation, no biologically relevant increase in the proportion of cells with structural aberrations was observed in either of the two experiments. With metabolic activation, the negative result obtained in the first experiment was not reproduced in the second experiment. Replicate slides were counted in each experiment, but only single cultures were exposed to the controls and to each concentration the test item. It is noted that there is considerable variation between the replicate slides (for example, high dose metabolic activation group replicates providing results of 0 and 8 in experiment I; mid-dose replicates in experiment II results 4 and 1 without MA, 5 and 10 with MA). It is assumed that this lack of reproducibility was the reason that extra cells were counted. Appropriate positive, solvent and medium controls were included and gave results within the range of the historical controls. It was concluded by the authors of the draft report that the test substance is positive for the induction of structural chromosome aberrations under the conditions of the test. The reviewer notes that the differences between replicate slides; the lack of dose response in experiment 1; the unexplained differences between the solvent and medium controls; the different results in experiments 1 and 2 all call into question the biological relevance of the results. In addition, the differences between replicates mean that the absence of duplicate cultures may have had an impact on the results.

Mutagenicity in mammalian cells: testing is not required as a positive result was obtained from the in vitro cytogenicity assay.

An in vivo micronucleus assay is proposed to investigate the potiential for clastogenicity observed in the in vitro assay.

Justification for classification or non-classification

There is insufficient information to reach a conclusion on classification.