2-chloropropane

Endpoint summary

Additional information

In the GLP compliant, key bacterial reverse mutation assay (equivalent to OECD guideline 471), IPC was tested at doses of 0, 8, 40, 200, 1000, or 5000 µg/plate in Salmonella typhimurium strains TA 98, TA 100, TA 1535, and TA 1537 both in the absence and presence of exogenous metabolic activation [rat liver S9 (compound used to induce cytochrome P450 enzymes was not reported)] (Creutziger, 1989).  The experiment was conducted in quadruplicate and an independent repeat experiment was performed. Acetone was used as the vehicle and positive controls were included in all incubations. No cytotoxicity was observed at any IPC concentration and no increases in the reverse mutation rate were noted in any strain either in the absence or presence of metabolic activation. Incubation with positive control substances in the absence or presence of metabolic activation resulted in anticipated increases in reverse mutation rates.

 

In a key, GLP compliant mammalian chromosome aberration test (according to OECD guideline 473), IPC was tested at doses of 0, 30, 300, or 800 µg/mL in human peripheral blood lymphocytes in the absence or presence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Heidemann, 1990).  Incubations at each concentration were done in duplicate; however, an independent repeat experiment was not performed.  Dimethyl sulphoxide (DMSO) was used as the vehicle control and ethylmethanesulfonate and cyclophosphamide were used as the positive control compounds in the absence and presence of metabolic activation, respectively. No cytotoxicity was observed and no chromosome damage was noted at any IPC concentration either in the absence or presence of metabolic activation. Incubations with the positive control compound resulted in anticipated increases in chromatid damage.

 

In a key, GLP compliant mammalian gene mutation assay (according to OECD guideline 476), IPC was tested at doses of 0, 80, 200, 400, or 800 µg/mL in the absence or presence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) in Chinese hamster lung fibroblast (V79) cells (Heidemann, 1990).  The experiment was conducted in duplicate and an independent repeat experiment was performed. DMSO was used as the vehicle and ethylmethanesulfonate and 7,12-dimethylbenz[a]anthracene were used as the positive control compounds in the absence and presence of metabolic activation, respectively. Cytotoxicity was not observed and increases in the mutant frequency were not noted at any IPC concentration either in the absence or presence of metabolic activation. Incubation with positive control substances in the absence or presence of metabolic activation resulted in anticipated increases in the mutation frequencies.

 

In a key, GLP compliant in vivo micronucleus assay (according to OECD guideline 474), IPC was administered via intraperitoneal (IP) injection to male and female NMRI mice at a single dose of 2,000 mg/kg body weight (Korn, 1989).  Corn oil was used as the vehicle and cyclophosphamide was administered via IP injection as the positive control compound. Animals were sacrificed 24, 48, or 72 hours after administration of the test article or controls (5 to 15 mice/sex/dose). No deaths were reported; however, sedation and piloerection were observed following test article administration. Statistically significant increases in the number of micronucleated polychromatic erythrocytes were not noted following IPC administration. The positive control compound caused anticipated increases in micronucleated polychromatic erythrocytes. 

 

In a GLP compliant in vivo unscheduled DNA synthesis assay (equivalent to OECD guideline 486), IPC was orally administered to male Wistar rats at doses of 0, 100, 330, or 1000 mg/kg body weight (5 males/dose) (Fautz, 1990).  Polyethylene glycol 400 was used as the vehicle and orally administered 2-acetylaminofluorene was used as the positive control compound. Following a post-exposure period of 12 to 14 hours, 1 rat receiving 1000 mg/kg body weight died; however, no clinical signs of toxicity were noted. In addition, no increases in the average nuclear grain count were observed at any IPC concentration.  Administration of the positive control compound resulted in an anticipated increase in the average nuclear grain count.

Short description of key information:

The genetic toxicity of isopropyl chloride (IPC) has been assessed in 3 in vitro studies (including a bacterial reverse mutation assay) as well as in 2 in vivo studies (a micronucleus assay and an unscheduled DNA synthesis assay).  Negative results were reported in all studies.  

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The submission substance produced negative results in both in vitro and in vivo genetic toxicity studies. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.5.