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Key value for chemical safety assessment

Additional information

In vitro, acetophenone was found not to induce gene mutations in a Salmonella typhimurium reverse mutation assay (Key study/guideline study: Sokolowski, 2006) and in a mouse lymphoma cell mutagenicity assay at the thymidine kinase locus (Key study/guideline study: Wollny et al., 2007) when tested up to cytotoxic concentrations. The absence of a mutagenic activity in bacteria is supported by further data from Salmonella typhimurium reverse mutation studies (Commoner, 1976; Elliger et al., 1984; Florin et al., 1980), from a mutagenicity assay with Escherichia coli strains being deficient and proficient in DNA repair (DNA polymerase activity) (Fluck et al., 1976), and from a DNA repair assay in Salmonella typhimurium TA 1535/pSK1002 (umu test) (Ono et al., 1991).

A clastogenic potential was indicated in an in vitro chromosome aberration test in V79 cells, only in the presence of metabolic activation and at test concentrations of at least 900 µg/mL (Key study/guideline study: Höpker, 2007). In contrast, there was no indication of a clastogenic activity in an in vivo micronucleus assay in peripheral blood erythrocytes after application up to the MTD (515 mg/kg bw by intraperitoneal injection) (Key study/guideline study: Hofman-Hüther, 2008).

There exists some weight of evidence from in vitro studies with artificial test conditions that acetophenone principally has the capacity to be activated in the presence of UV radiation (photosensitising effect) or oxidative agents to induce modifications in DNA or nucleotides or in repair deficient strains of E. coli (Demidov et al., 1991; Epe et al., 1993; Adam et al., 2001, 2002; Mennigmann, 1972.; Fix and Bockrath, 1983; Midorikawa et al., 2004). All data come from test systems that are not validated for assessment of a mutagenic potential under biologically relevant conditions. Up to now, there are no data to assess if mechanisms of photosensitization and photooxidation play any role in mammalian cells in vitro or in vivo.

Short description of key information:
In vitro assays:
Absence of gene mutation without and with metabolic activation: S. typhimurium reverse mutation assay (Key study: Sokolowski, 2006), mouse lymphoma mutagenicity assay (Key study: Wollny, 2007)
Clastogenic effect in the presence of metabolic activation: Chromosomal aberration test in V79 cells (Key study: Höpker, 2007)
In vivo assays:
Absence of clastogenic effect in micronucleus test in mouse peripheral blood erythrocytes (Key study: Hofman-Hüther, 2008)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to CLP and EC regulation 1272/2008 no classification of acetophenone for germ cell mutagenicity results. Based on the available key studies, there is no mutagenic potential in vitro. There is no evidence of a clastogenic effect in somatic cells in vivo in a guideline study, so that the indication of a possible clastogenic effect from an vitro study in the presence of metabolic activation is not supported in the in vivo condition.