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Key value for chemical safety assessment

Additional information

In vitro studies:

Ames test - In this key study for in vitro genetic toxicity (Machado et al, 1989) there was no guideline specified, however it was considered to be comparable to OECD Guideline 471 (Bacterial Reverse Mutation Assay). The study was conducted in line with GLP. A reliability rating of 1 according to the criteria of Klimisch, 1997.

Mammalian Cell Gene Mutation Test - In this key study for in vitro genetic toxicity (Condray, 1987) there was no guideline specified, however it was considered to be comparable to OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test).

The study is considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997 as the information was obtained from the 2006 SIDS dossier due to the original report being unavailable.

Supporting infomation:

The supporting study (Schörberl, 1992, ames study) is also avaiable for this endpoint. The study is considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997 as the information was obtained from the 2006 SIDS dossier due to the original report being unavailable.

Under the conditions of this study, the test material was not mutagenic.

The supporting study (Condray, 1987, ames study) is also avaiable for this endpoint. The study is considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997 as the information was obtained from the 2006 SIDS dossier due to the original report being unavailable.

No statistically significant increases in mutation frequency were observed at dose levels of 1.0 to 1000 μg/plate in all strains with and without an S-9 metabolic activation system.

In vivo:

The key study for in vivo genetic toxicity (Condray, 1987) was considered to be comparable to OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test).

The study is considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997 as the information was obtained from the 2006 SIDS dossier due to the original report being unavailable.


Short description of key information:
Ames test:
The test material was diluted with 25% Pluronic F127 (w/w in ethanol) and tested in the histidine-deficient strains of Salmonella typhimurium TA98, TA100, TA1535, and TA1537 at dose levels of 0.1 to 10 mg/plate with and without metabolic activation provided by Aroclor-induced rat liver S-9. The test material appeared to form a stable emulsion with Pluronic F127 and the dilutions were well dispersed in the top agar; however, after incubation, test material was observed on the surface of the top agar at 10 mg/plate. The test material was cytotoxic at 10 mg/plate to TA100 with and without S-9 and at > 3.3 mg/plate to TA1535 with S-9.
No statistically significant increases in mutant frequency were observed in any strain. Under the conditions tested, the test material was not mutagenic to strain TA98, TA100, TA1535, or TA1537 with or without metabolic activation.

Mammalian Cell Gene Mutation Test:
In this study the test material was not mutagenic when tested in the CHO/HGPRT forward mutation assay at concentrations up to 10 μg/ml in the presence of metabolic activation system and up to 0.1 μg/ml in the absence of metabolic activation system.

In vivo:
Mortality was observed at the high dose, and reduced body weight gain was observed in the mid- and high-dose groups. There was no evidence of chromosome damage as measured by increases in chromosome aberrations, altered mitotic index, or chromosome number when compared to the concurrent control group. In the cyclophosphamide-treated positive control group, a significant increase in the average number of aberrations, percent of cells with aberrations, and decreased mitotic index was observed confirming the sensitivity of the assay. Under the conditions of this study the test material is not clastogenic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The results for the key parameters chosen for genetic toxicity were negative and so the criteria set out in Directive 67/548/EEC and also Regulation (EC) no 1272/2008 do not apply, therefore classification for genetic toxicity was not considered to be necessary.