Propylene carbonate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

One reliable AMES test was available (Klimisch 2), covering bacterial reverse mutation assay. One reliable study was available (Klimisch 1) for DNA damage and repair assay and unscheduled DNA synthesis in mammalian cells in vitro was available (Klimisch 2). None of the available genotoxicity studies (Two in vitro ( Ames test and DNA damage and repair assay)) indicated any genotoxic or mutagenic effects.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

One reliable micronucleus test was available (Klimisch 2). The erythrocyte micronucleus test indicated no genotoxic or mutagenic effects.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Genetic toxicity in vitro:

Bacterial reverse mutation assay:

Huntsman performed an AMES (liquid pre-incubation) test with S typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 with and without metabolic activation (Pharmakon Research International, 1985).

Following test concentrations were applied: 50, 167, 500, 1667 and 5000 µg/plate (in duplicate). Solvent control and positive controls were run in triplicate. There were no observed increases in mutation frequency with and without metabolic activation at the tested dose levels. All solvent and positive controls used induced mutant frequency values which were within the acceptable limits of mean historical data. Cytotoxicity was not determined in this study.

DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro:

Barfknecht (1985) studied the gene mutation potential in rat hepatocytes (adult male F344 rats) without metabolic activation. Following doses were evaluated in triplicate: 40, 133, 400, 1333 and 4000 µg/well. A negative control (WME medium), vehicle control (water) and a positive control (1E-05 molar 2 -acetamidofluorene) were scored as well. Under the conditions of this study, the test substance was not genotoxic in the hepatocyte primary culture/DNA repair test. This conclusion is based upon the finding of the inability of the test substance to produce a mean nuclear grain count of 5 or greater than the vehicle control mean net nuclear grain count at any level of concentration.

Cytogenicity test:

An in vitro cytogenicity study in mammalian cells does not usually need to be conducted if adequate data from an in vivo cytogenicity test are available. Sorg (1986) performed an in vivo micronucleus test on CD1 mice (IUCLID section 7.6.2). Therefore, it is not necessary to perform an in vitro cytogenicity test for propylene carbonate.

Mammalian cell gene mutation assay:

An in vitro UDS and in-vivo micronucleus test were performed which gave negative results in mammalian cells.Therefore, no mammalian cell gene mutation assay was performed with propylene carbonate.

Genetic toxicity in vivo:

In vivo micronucleus test:

Sorg (1986) performed an in vivo micronucleus test in male and female CD1 -mice via single intraperitoneal administration of 1666 mg/kg propylene carbonate (nominal concentration). Concurrent vehicle (distilled water) was used as a control. Triethylenemelamine (0.5 mg/kg) was used as a positive control substance. 5 animals per sex and per dose were tested. Bone marrow of the femur was evaluated. Results in the initial micronucleus test indicated a statistically significant increase in the incidence of micronuclei in animals administered 1666 mg/kg bw and sacrificed at 72 hours. The results of an additional re-test with 10 males and 10 females (with concurrent controls) were negative in the micronucleus test at a dose level of 1666 mg/kg at all of the time intervals evaluated. The findings are based on the inability of the test article to give a reproducible statistically significant increase in the incidence of micronuclei per 1000 polychromatic erythrocytes per animal in the treated group versus the negative control group under the conditions of this assay. Based on the overall results, the test article was negative in the micronucleus test at a dose level of 1666 mg/kg administered in single intraperitoneal doses with sacrifice times of 30, 48 and 72 hours.

Justification for classification or non-classification

Based on the available data and according to the criteria of the CLP Regulation (EC) 1272/2008, propylene carbonate should not be classified for mutagenicity.