Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

OECD TG 471, 2016 - The study was performed to the requirements of OECD Guideline 471, EU Method B13/14, US EPA OCSPP 870.5100 and Japanese guidelines for bacterial mutagenicity testing under GLP, to evaluate the potential mutagenicity of the test substance in a bacterial reverse mutation assay using S.typhimurium strains TA98, TA100, TA1535, TA1537 and E.coli strain WP2uvrA- in both the presence and absence of S-9 mix. The test strains were treated with the test item at eight dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolizing system (10% liver S9 in standard co-factors). Since the test item had unknown volatility all testing was performed using the pre-incubation modification. The experiment was repeated on a separate day using fresh cultures of the bacterial strains and fresh test item formulations. The vehicle (dimethyl sulphoxide) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. The maximum dose level of the test item in the first experiment was selected as the maximum recommended dose level of 5000 μg/plate. There were no toxicologically significant increases in the frequency of revertant colonies recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation in Experiment 1. Small, statistically significant increase in TA1535 revertant colony frequency were noted in the absence of S9-mix at 150 μg/plate and to TA98 at 500 μg/plate in the presence of S9-mix. These increases were considered to have no biological relevance because weakened bacterial background lawns were also noted at the same concentrations. Similarly, no toxicologically significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 2. A small, statistically significant increase in TA1535 revertant colony frequency was also observed in the absence of S9-mix at 15 μg/plate in this test. This increase was considered to be of no biological relevance because there was no evidence of a dose-response relationship or reproducibility. the individual revertant colony counts at 15 μg/plate were within the in-house historical untreated/vehicle control range for the tester strain and the fold increase was only 1.6 times the concurrent vehicle control. Under the conditions of this study, the test substance was considered non-mutagenic.


Justification for selection of genetic toxicity endpoint
Study selected is an in vitro study (Klimisch 1)

Short description of key information:
negative, in vitro bacterial reverse mutation (with and without S-9 activation), OECD TG 471, Envigo Research Limited 2016

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for mutagenicity