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3 Genetic Toxicity studies were conducted with and without activation according to the guidelines noted above. In all cases, no evidence of mutagenic activity was seen. Control materials induced the appropriate responses in all tests so the tests are considered valid.

 

 

C4-Acrylate was tested in the Salmonella typhimurium reverse mutation assay with four histidine-requiring strains of S.typhi TA1535, TA1537, TA100 and TA96) and in the Escherichia coli reverse mutation assay with a tryptophan-requiring strain of Escherichia coli Wp2uvrA. The test was performed in two independent experiments in the presence and absence of S9-mix. In the dose range finding test, the test article was tested up to concentrations of 5000 micrograms/plate with and without S9-mix in the trains TA100 and WP2uvrA. The test article precipitated on the plates at dose levels of 3330 and 5000 micrograms/plate in the presence of S9-mix. In tester strain Wp2uvrA, no toxicity was observed at all concentrations tested. In the first and in the second mutation assay, the test article was tested up to concentrations of 3330 micrograms/plate in the absence and presence of S9-mix. The test article precipitated on the plates at this dose level. Toxicity was observed in test strains TA1537 and TA100 in the presence of S9-mix in the second mutation assay at the highest concentration tested. In all other strains tested no toxicity was observed at any of the concentrations tested. The presence of 5 and 10% (v/v) S9 activation did not influence these findings. The test article did not induce a dose related, two-fold increase in the number of revertant Histidine+ colonies in each of the four S.typhi test strains and in the number of revertant (trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in an independently repeated experiment. Based on the results of these studies, the test article is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay. 

 

An in vitro mammalian cell gene mutation test with L5178Y mouse lymphoma cells was conducted on the test article to determine its mutagenic potential. The test was performed in two independent experiments in the absence and presence of S9-mix (rat liver S9-mix induced by a combination of phenobarbital and beta-naphthoflavone) to determine the test article's effect on the induction of forward mutation at the thymidine-kinase locus (TK-locus) of mouse lymphoma cells. In the first experiment the test article was tested up to concentrations of 40 and 500 ug/mL in the absence and presence of 8% (v/v) S9-mix, respectively. The incubation time was 3 hours. The test article was tested up to cytotoxic levels of 92 and 85% in the absence and presence of S9-mix, respectively. The test article precipitated in the culture medium at dose levels of 200 ug/mL and above. In the second experiment the test article was tested up to concentration of 45 and 600 ug/mL in the absence and presence of 12% (v/v) S9-mix, respectively. The incubation times were 24 hours and 3 hours for incubations in the absence and presence of S9-mix, respectively. The test article was tested up to cytotoxic levels of 81 and 76% in the absence and presence of S9-mix, respectively. The test article did not induce a biologically relevant significant increase in the mutation frequency in either experiment conducted. The results were confirmed in an independent repeat experiment with modifications in the duration of treatment time. It is concluded that the test article is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described in this report.

 

Evaluation of the ability of C4 Acrylate to induce chromosome aberrations in cultured peripheral human lymphocytes (with repeat experiment) in the presence and absence of a metabolic activation system (S9-mix) was performed according to OECD Guideline 473. In the first cytogenetic assay the test article was tested up to 100 ug/mL for a 3 hour exposure time with a 24 hour fixation time in the absence and presence of 1.8% (v/v) S9-fraction. The test article precipitated in the culture medium at this dose level. In the second assay the test article was tested up to 100 ug/mL for a 24 hour continuous exposure time with a 24 hour fixation time and up to 140 ug/mL for a 48 hour continuous exposure time with a 48 hour fixation time in the absence of S9-mix. Appropriate toxicity was reached at those dose levels. The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical data range. Positive control chemicals, mitomycin C and cyclophosphamide, both produced a statistically significant increase in the incidence of chromosomal aberrations indicating the test conditions were adequate. The test article did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in the absence and presence of S9-mix in either of the independently repeated experiments. It can be concluded that the test substance does not disturb mitotic processes and cell cycle progression and does not induce numerical chromosome aberrations under the experimental conditions described in this report.


Short description of key information:
Bacterial Reverse Mutation Assay: Non-mutagenic when tested according to OECD 471.

Chromosome Aberration: Negative when tested according to OECD 473

Mammalian Cell Gene Mutation: Negative when tested according to OECD 476

Endpoint Conclusion:

Justification for classification or non-classification

The test results do not meet the criteria for classifying C4 Acrylate as a Germ Cell Mutagen.