(chloromethyl)vinylbenzene

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The compound vinylbenzyl chloride was considered to be not mutagenic with five Salmonella typhimurium strains (TA98, TA100, TA1535, TA1537, TA1538), both in the presence and in the absence of a metabolic activation system, when tested up to a toxic concentration (KS_in vitro_Bacterial reverse mutation assay_1976). This result is in line with another study, showing negative results for vinylbenzyl chloride with Salmonella strains TA-1530 and G-46 (SS_in vitro_Bacterial reverse mutation assay_Salmonella_1973).

In Saccharomyces cerevisiae D3, the substance vinylbenzyl chloride at a concentration of 5% (w/v) only slightly increased the number of recombinants (3-fold), whereas the positive control ethylmethanesulfonate caused a 36.2-fold increase under similar test conditions. Therefore, the mutagenic response induced by vinylbenzyl chloride in the in vitro Saccharomyces D3 test was considered as an equivocal reponse (SS_in vitro_Miotic Recombination Assay_Saacharomyces cerevisiae_1973). This is supported by results reported by Simmons (SS_in vitro_Mitotic recombination assay_Saccharomyces cerevisiae_1976). In this study, the test substance vinylbenzyl chloride caused a slight and non-reproducible increase in mitotic recombination in D3 (with and without metabolic activation) at a compound concentration of 0.01%, whereas 0.02% yielded a slighly increased reponse (4 -12 fold) in one experiment, accompagnied by a clearly increased cytotoxicity. Concentrations above 0.02% were toxic and could thus not be analyzed.

Obtained results for test concentrations of 0.01 and 0.02% do not allow for a clear derivation of a positive result and are thus considered as equivocal and questionable. In addition, as this assay in this yeast strain is not a standard approach to in vitro genotoxicity testing, final conclusions on a genotoxicity potential of vinylbenzyl chloride cannot be derived from these data.

Considering the negative results obtained for vinylbenzyl chloride in in vivo studies on chromosomal aberrations in rats after oral (KS_in vivo_Mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration_feeding study_rats_1972) and inhalative (SS_in vivo_Mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration_inhalation_rats_1973) exposure, the negative result on the mutagenic potential after oral exposure of mice reported by Sibinovic (SS_in vivo_Subacute host-mediated assay for mutagenic activity_oral_mice_1973), and the negative result in the carcinogenicity study in rats (KS_Carcinogenicity_Two-year inhalation study_rats_1976), the substance vinylbenzyl chloride is considered as not genotoxic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

In a cytogenetics study in rats, doses of 0.63, 6.3, and 63 mg/kg bw/day of vinylbenzyl chloride were orally administered on 5 consecutive days (5 animals per treatment group, 3 animals in the negative control group, 5 animals in the positive control group administered triethylene melamine). No abnormal signs or pathology were noted in the animals at the dose levels employed, and no detectable significant aberrations of the bone marrow metaphase chromosomes of rats were observed (KS_in vivo_Mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration_feeding study_rats_1972).

Groups of male Sprague-Dawley rats were exposed to atmospheres of 0.1 or 1.0 ppm vinylbenzyl chloride in air for six months (6 hous per day, 5 days per week). On day 5 of the post-exposure period 4 rats from each group were submitted for cytogenetic evaluation of bone marrow cells which was performed after intraperitoneal injection of 4 mg/kg bw colchicine four hours prior to sacrifice. No dose relationship with breaks or gaps was noted. The only severe chromosomal aberration found was a dicentric in a control animal. In conclusion, these data are considered as a negative test result. However, no positive control was included in this study (SS_in vivo_Mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration_inhalation_rats_1973).

In addition, in a subacute in vivo host-mediated assay for mutagenic activity, mutagenic potential of vinylbenzyl chloride following oral exposure of mice was analysed using Salmonella strains TA1530 and G-46, and Saccharomyces D-3. Results obtained for the test substance vinylbenzyl chloride were considered as negative (SS_in vivo_Subacute host-mediated assay for mutagenic activity_oral_mice_1973).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

Based on negative test results in the bacterial reverse mutation assay and rodent bone marrow chromosome aberration tests after sub-acute oral and chronic inhalation exposure, the substance is not classified for mutagenicity in accordance to Regulation (EC) No 1272/2008 (CLP Regulation).