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Key value for chemical safety assessment

Additional information

The genotoxic potential of the test substance was assessed in three in vitro studies in bacteria and mammalian cells.

In the bacterial reverse mutation assay (Ames test, OECD 471) the substance was tested with and without metabolic activation in the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 (Wirnitzer, 2005). A plate incorporation test and a pre-incubation test with concentrations up to 5000 µg per plate were performed. The exposure duration was 48 hrs for both methods, with 20 minutes pre-incubation in the latter test. Substance precipitation started at 1581 µg/plate, but an assessment was possible up to and including 5000 µg/plate. The results showed no biologically relevant effects.

The chromosome aberration test (OECD 473) was performed using Chinese hamster lung fibroblasts (V79) exposed to the test substance with and without metabolic activation at various exposure and harvesting times (Thum, 2005). In test 1, cells were exposed to 7, 14 and 28 ug/mL for 4 hrs with and without S9 -mix, and harvested 18 hrs after treatment started. In test 2, 28 ug/mL was used and cells were exposed for 30 hrs with and without S9 -mix and harvested 30 hrs after treatment started. Finally, in test 3, cells were exposed to 7, 14 and 28 ug/mL for 18 hrs without S9 mix, and the harvest time was 18 hrs after treatment started. Without S9-mix cytotoxic effects were observed at 28 ug/mL (18 hours treatment), with S9-mix cytotoxic effects were observed at 28 ug/mL after 4 hours treatment. Precipitation occurred in the medium at the concentration 7 ug/mL and above after 4 hrs treatment without S9 -mix, while with S9-mix precipitation was noted from 14 ug/mL. After 18 hrs treatment precipitation occurred at 7 ug/mL and above. There was no increase in chromosomal aberrations and the test substance is therefore considered not to be clastogenic for mammalian cells in vitro.

In an in vitro mammalian cell gene mutation assay, the incidence of gene mutations on the HPRGT locus in Chinese hamster lung cells (V79) exposed to the test substance was tested with and without metabolic activation by S9-mix (Herbold, 2002). In the preliminary cytotoxicity assay the concentration range 0.1 - 200 ug/mL was tested with and without S9 -mix to establish the optimal tests concentrations. In the main assay the range 2 - 128 ug/mL was used, with and without S9 -mix. Precipitation was noted at concentrations at and above 64 ug/mL, while no cytotoxicity was observed. The test substance did not cause an increased mutation frequency in this study.

Based on the available studies, the test substance is not genotoxic in vitro.


Justification for selection of genetic toxicity endpoint
No study was selected, since all available in vitro genetic toxicity studies were negative.

Short description of key information:
Bacterial reverse mutation assay (OECD 471): negative
Cytogenicity (Chromosomal aberration in mammalian cells OECD 473): negative
Gene mutation in mammalian cells ( HGPRT assay OECD 476): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data are conclusive but not sufficient for classification according to the criteria of DSD (67/548/EEC) and CLP (1272/2008/EC).