Acetone

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Genotoxicity in vitro:

No genotoxicity activity of acetone was evident in vitro in the following three key studies:

The genotoxic potential of acetone was investigated in Salmonella typhimurium strains TA 1535, TA 1537, TA 97, TA 98 and TA 100 with and without metabolic activation with a test protocol comparable to OECD guideline 471. Test results were negative except for a questionable result with the strain TA 97 occurring only after metabolic activation with 30 % rat liver S-9 but not in the presence hamster liver S-9 or 10 % rat liver S-9. In summary, there was no evidence of a genotoxic potential of acetone in the Salmonella typhimurium reverse mutation assay with and without metabolic activation up to a concentration of 10 mg/plate (NTP, 1986; Zeiger et al., 1992). In an in vitro chromosome aberration test in CHO cells with and without metabolic activation according to a test protocol similar to OECD Guideline no increased incidence of structural aberrations was found up to concentrations of 5 mg acetone/mL (Loveday et al., 1990; NTP, 1986). The absence of a mutagenic potential of acetone was indicated in the mouse lymphoma mutagenicity assay performed only in the absence of a metabolic activation system with a test protocol similar to OECD Guideline 476 (Amacher et al., 1980).

Weight of evidence further confirms the absence of genotoxic activity from further genotoxicity assays (For this compilation the reliability of the individual studies was not checked or the reliability may be 3 or 4). There were no indications of a genotoxic potential in the following test systems:

- reverse mutation assay in S. typhimurium

- SOS chromotests in S. typhimurium and E. coli

- assays on prophage induction or DNA binding in E. coli

- recombination assay in B. subtilis

- chromosomal malsegregation, point mutations and mitotic recombination in S. cerevisiae

- forward mutation in S. pombe

- mutagenicity assay in mouse lymphoma cells and Chinese hamster lung fibroblasts

- chromosomal aberration in CHO cells and human lymphocytes

- sister chromatid exchange in CHO cells and human lymphocytes

- unscheduled DNA synthesis in human skin cells and bovine lymphocytes

- DNA strandbreaks in rat hepatocytes

Genotoxicity in vivo:

No genotoxic activity of acetone was evident in vivo based on a weight of evidence approach:

Groups of 10 B6C3F1 mice, that had continuously been exposed to 0, 0.5, 1 or 2 % acetone in drinking water for 13 weeks, were scored for induction of micronuclei in normochromatic erythrocytes in peripheral blood. Based on actual water consumption these concentrations correspond to dosages of 1,569, 3,023, and 5,481 mg/kg bw/d in male mice and dosages of 2,007, 4,156, and 5,945 mg/kg bw/d in female mice (values reported in NTP, 1991). No indication of a clastogenic activity of acetone was found (NTP, 1993).

A dose of 865 mg acetone/kg bw (2/3 of the LD50) was intraperitoneally administered to Chinese hamsters (5 males and 5 females per timepoint) and the percentage of polychromatic bone marrow erythrocytes with micronuclei was investigated at sampling timepoints of 12, 24, 48, and 72 hours. There was no increase of the rate of micronuclei at any timepoint (Basler, 1986).

Short description of key information:
Bacterial mutagenicity assay: Salmonella typhimurium strains TA 1535, TA 1537, TA 97, TA 98 and TA 100 with and without metabolic activation (OECD Guideline 471): negative (Key study: NTP, 1986)
Mammalian cell mutagenicity assay in vitro: mouse lymphoma cells without metabolic activation (OECD Guideline 476): negative (Key study: Amacher et al., 1980)
Mammalian cell clastogenicity assay in vitro: chromosome aberration test in CHO cells with and without metabolic activation (OECD Guideline 473): negative (Key study: NTP, 1986)
In vivo micronucleus test in peripheral blood erythrocytes: mouse, 0, 0.5, 1 or 2 % acetone in drinking water for 13 weeks: negative (Weight of evidence: NTP, 1993)
In vivo micronucleus test in bone marrow erythrocytes: Chinese hamster, 865 mg acetone/kg bw i.p.: negative (Weight of evidence: Basler, 1986)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

There is no classification for genetic toxicity based on negative test results in in vitro and in vivo test systems.