4-hydroxymethyl-1,3-dioxolan-2-one

Endpoint summary

Additional information

Genetic toxicity: in vitro

Three in vitro studies were selected as key studies: a bacterial reverse mutation assay (Ames test), an in vitro chromosome aberration test and a gene mutation test.

 

Bacterial reverse mutation assay:

An Ames-test was performed according to a method equivalent to OECD Guideline 471 and in compliance with the principles of GLP with the following Salmonella typhimurium strains: TA 1535, TA 1537, TA 98, TA 100 and Escherichia Coli strain WP2uvrA (BioReliance, 2007).

Glycerine carbonate was tested with and without a metabolic activation system, according to the plate incorporation method. Bacteria were exposed to glycerine carbonate at five dose-levels selected from a preliminary toxicity test: 50, 150, 500, 1500 and 5000 μg/plate. After 48 to 72 hours of incubation at 37°C, the revertant colonies were scored. No positive mutagenic responses were observed with any of the tester strains in either the presence or absence of S9 activation. Neither precipitate nor appreciable toxicity was observed.

 

In vitro mammalian chromosome aberration test:

An in vitro chromosome aberration test with the read-across substance glycerol was conducted according to a method equivalent to OECD Guideline 473 (Doolittle, 1988).

The test material was evaluated in the Chinese hamster ovary assay with and without metabolic activation, at the following dose levels: 100, 200, 400, 600, 800 and 1000 µg/mL.

According to the conditions of the experiment, the test item did not induce a statistically significant increase in the frequency of cells with chromosome aberrations in either the absence or presence of a metabolic activation system. No cytotoxicity has been observed.

Mammalian cell gene mutation test:

A mammalian cell gene mutation test with the read-across substance glycerol was conducted according to a method equivalent to OECD Guideline 476 (Doolittle, 1988).

The test material was evaluated in the Chinese hamster ovary assay with and without metabolic activation, at the following dose levels: 100, 200, 400, 600, 800 and 1000 µg/mL.

The results this cell gene mutation test indicate that, under the conditions of this study, glycerine carbonate was concluded to be negative with and without metabolic activation. No cytotoxicity has been observed at 1000 µg/plate, the highest concentration tested.

Genetic toxicity: in vivo

No in vivo genetic toxicity study has been conducted with glycerine carbonate. However, no positive result was obtained in the in vitro genotoxicity tests with this substance and the read-across substance glycerol. Therefore, it is not necessary to perform an in vivo genetic toxicity test with glycerine carbonate (column 2 adaptation, Annex IX, section 8.4).

 

Justification for selection of genetic toxicity endpoint
Studies performed in accordance with OECD guidelines and relevant regarding REACH process.

Short description of key information:
Genetic toxicity in vitro:
Three in vitro key studies have been identified: one bacterial reverse mutation test (K1, Bioreliance, 2007) performed with the substance glycerine carbonate, one in vitro mammalian chromosome aberration test (K2, Doolittle, 1988) performed with the read-across substance glycerol and one gene mutation test (K2, Doolittle, 1988).

The bacterial reverse mutation assay was performed according to a method equivalent to OECD Guideline 471 in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and E. coli strain WP2 uvrA. According to the results of the study, glycerine carbonate is not mutagenic in the Ames test with and without metabolic activation.

No chromosome aberration test is available for glycerine carbonate but data are available from the read-across substance glycerol. The test was performed with and without metabolic activation according to a method equivalent to OECD Guideline 473. According to the results of the study, glycerol is not mutagenic in the chromosome aberration test with and without metabolic activation.

No gene mutation test is available for glycerine carbonate but data are available from the read-across substance glycerol. The test was performed with and without metabolic activation according to a method equivalent to OECD Guideline 476. According to the results of the study, glycerol is not mutagenic in the gene mutation test with and without metabolic activation.

Genetic toxicity in vivo:
No in vivo genetic toxicity study has been conducted with glycerine carbonate. However, no positive result was obtained in the in vitro genotoxicity tests with this substance and the read-across substance glycerol. Therefore, it is not necessary to perform an in vivo genetic toxicity test with glycerine carbonate (column 2 adaptation, Annex IX, section 8.4)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data on glycerine carbonate and the read-across substance glycerol and the criteria of the DSD and CLP Regulation, glycerine carbonate should not be classified as a mutagenic agent.