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Additional information

In a GLP compliant mammalian gene mutation assay (equivalent to OECD guideline 476), the ability of IPA to increase mutation frequencies was investigated in Chinese Hamster Ovary (CHO) cells in the absence and presence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Young, 1990).  Twelve plates were used per dose and 3 or 2 independent experiments were conducted in the absence or presence of metabolic activation, respectively. The doses used in each experiment were as follows:

1.      0, 0.5, 1.0, 2.0, 3.0, 4.0, or 5.0 mg/mL in the absence and presence of metabolic activation (Trial 1);

2.      0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, or 5.0 mg/mL and 0, 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5, or 5.0 mg/mL in the absence and presence of metabolic activation, respectively (Trial 2);

3.      0, 1.0, 2.0, 3.0, 4.0, 4.5, or 5.0 mg/mL in the absence of metabolic activation (Trial 3).

Sterile, deionized water was used as the vehicle and 5-bromo-2-deoxyuridine and 3-methylcholanthrene were used as the positive control compounds in the absence and presence of metabolic activation, respectively. No cytotoxicity and no increase in the mutant frequency were observed at any IPA concentration either in the absence or presence of metabolic activation. Additionally, incubation with the positive control substances in the absence or presence of metabolic activation resulted in anticipated increases in the mutation frequencies.

In a non-GLP bacterial reverse mutation assay (equivalent to OECD guideline 471), IPA was tested at doses of 0; 100; 333; 1,000; 3,333 or 10,000 µg/plate in Salmonella typhimurium strains TA 97, TA 98, TA 100, TA 1535, and TA 1537 both in the presence and absence of exogenous metabolic activation (Aroclor 1254-induced rat and hamster liver S9) (Zeigeret al., 1992).  The incubations were conducted in triplicate and an independent repeated experiment was performed. Distilled water was used as the vehicle and positive controls were included in all incubations. No cytotoxicity was observed and no increase in the reverse mutation rate was observedat at any IPA concentration either in the presence or absence of metabolic activation. Incubation with positive control substances in the presence or absence of metabolic activation did not always result in anticipated increases in reverse mutation rates. As a result this study is considered reliable with restrictions.

In a GLP compliant micronucleus assay (equivalent to OECD guideline 474), IPA was administered via intraperitoneal (IP) injection to male and female ICR mice at doses of 350; 1,173; 2,500, or 3,500 mg/kg body weight (Ivett, 1991).  Sodium chloride was used as the vehicle and oral (gavage) cyclophosphamide was administered as the positive control compound. Mice were sacrificed at 24, 48, or 72 hours after dosing (5 mice/sex/time point). Twenty-two hours following dosing, most of the mice receiving 3,500 mg IPA/kg body weight died. Due to this toxicity, the 3,500 mg/kg body weight dose level was eliminated from the study. Deaths and clinical signs also were noted in mice receiving 2,500 mg/kg body weight; however, findings in the groups receiving 350 or 1,173 mg IPA/kg body weight were not reported. No statistically significant increases in the number of micronucleated polychromatic erythrocytes were noted at any dose level at any time point. The evaluation of 1,000 polychromatic erythrocytes per animal instead of 2,000 rendered this study reliable with restrictions.


Short description of key information:
The genetic toxicity of isopropanol (IPA) has been assessed in 2 in vitro studies and an in vivo assay. Negative results were reported in all studies.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.