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Key value for chemical safety assessment

Additional information

Genetic toxicity

The genetic toxicity of chloroprene, and its metabolites has been extensively investigated over many years in guideline and pre-guideline studies in vitro (using bacterial and mammalian test systems) and in vivo. Both negative and positive mutagenic responses, in the presence and absence of metabolic activation have been reported in mutagencity tests using chloroprene in bacterial. Although chloroprene has given positive results in some bacterial mutagenesis assays, it has been propsed that the mutagenic effects seen in these studies may arise from reactive metabolites formed by microsomal mixed function oxidases or from the breakdown products of aged chloroprene. The primary metabolite of chloroprene, 1-CEO, was mutagenic to 4 strains of S. typhimurium in a bacterial reverse mutation assay.While a reactive metabolite of chloroprene, 1-CEO may induce mutations in vitro in bacterial strains (Himmelsteinet al. 2001a), neither the administration of chloroprene (Drevon and Kuroki1979) nor this epoxide metabolite (Himmelsteinet al. 2001a) was genotoxic or mutagenic in in vitro mammalian cell gene mutation or micronucleus cell assays, respectively, in Chinese hamster V79 cells.

Chloroprene was not genotoxic when tested in vivo (several pre-guideline and published studies: NTP 1998c,d,e, Willems 1978, Immel 1978a,b,c. These data indicate that the reactive metabolites formed from chloroprene are effectively detoxified in vivo in the concentration ranges studied.

Overall it is concluded that chloroprene is no in vivo mutagen. Recent findings on K-ras proto-oncogen mutations in lung and Herderian gland neoplasms were indicative for mutagenic events involved (Sills 1999) but not conclusive, as K-ras mutations might be associated with other processes (e. g. cell proliferation secondary to cytotoxicity or selection for pre-existing mutations). For these reasons, no classifiaction for genotoxicity or mutagenicity for chloroprene is indicated.


Short description of key information:
The genetic toxicity of chloroprene, and its metabolites has been extensively investigated over many years in guideline and pre-guideline studies in vitro (using bacterial and mammalian test systems) and in vivo. Both negative and positive mutagenic responses, in the presence and absence of metabolic activation have been reported in mutagencity tests using chloroprene in bacterial. Although chloroprene has given positive results in some bacterial mutagenesis assays, it has been propsed that the mutagenic effects seen in these studies may arise from reactive metabolites formed by microsomal mixed function oxidases or from the breakdown products of aged chloroprene. The primary metabolite of chloroprene, 1-CEO, was mutagenic to 4 strains of S. typhimurium in a bacterial reverse mutation assay. While a reactive metabolite of chloroprene, 1-CEO may induce mutations in vitro in bacterial strains (Himmelstein et al. 2001a), neither the administration of chloroprene (Drevon and Kuroki1979) nor this epoxide metabolite (Himmelstein et al. 2001a) was genotoxic or mutagenic in in vitro mammalian cell gene mutation or micronucleus cell assays, respectively, in Chinese hamster V79 cells.

Chloroprene was not genotoxic when tested in vivo (several pre-guideline and published studies: NTP 1998c,d,e, Willems 1978, Immel 1978a,b,c). These data indicate that the reactive metabolites formed from chloroprene are effectively detoxified in vivo in the concentration ranges studied.

Chloroprene is not classified in europe as mutagen.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Chloroprene is not classified for genotoxicity or mutagencity according to EU classification legislation.