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Key value for chemical safety assessment

Additional information

Bacterial reverse mutation:

Hargitai J (2010) was selected as the key study for this data requirement as it is the most recent study, performed to up to date guidelines and in compliance with GLP. The study was assigned a reliability score of 1.

Jagannath D.R. (1982) was provided as a supporting study to Hargitai J (2010), the methods employed in the study were similar to the current OECD guidelines, however, the study did not use one of the additional cross linking in recommended by the revised guideline. The study was assigned a reliability score of 2. The results reported in the study were in agreement with those reported in the key study.

 

Mammalian cell in vitro mutagenicity:

Yang LL (1987) was provided as the key study for this data requirement. The study was performed to a method similar to OECD 476 and in compliance with GLP. The study was considered reliable and assigned a reliability score of 1.

Four chromosomal aberration studies, three studies by SanSebastian J.R. (1987) (performed on different batches of the same cell line) and one study by Putman DL (1987). SanSebastian JR (1987) was selected as the key study for this data requirement. Three chromosomal aberration studies (performed on different batches of DBS concurrently) was performed to methods comparable to OECD guideline 473 and in compliance with GLP. One study by Putman DL (1987) also conducted to OECD guideline 473 provided equivocal results.

 

Mammalian cell cytogenicity:

Curren RD (1987) was provided as the key study for this data requirement, the study was performed to methods comparable to the OECD guideline 482 and in compliance with GLP. The study was assigned a reliability score of 1 and considered adequate to fulfil the endpoint.

Justification for selection of genetic toxicity endpoint

No single study was selected as the genetic toxicity of the substance is assessed using different studies that address different modes of action and effects and are therefore not comparable.

Short description of key information:

Mutagenicity:

The test substance Great Lakes DBS was tested for potential mutagenic activity using the Bacterial Reverse Mutation Assay. The experiments were carried out using histidine-requiring auxotroph strains of Salmonella typhimurium (Salmonella typhimurium TA98, TA100, TA1535 and TA1537), and the tryptophan-requiring auxotroph strain of Escherichia coli (Escherichia coli WP2 uvrA) in the presence and absence of a metabolic activation system (S9 fraction). The study included a Preliminary Solubility Test, a Preliminary Range Finding Test (Informatory Toxicity Test), an Initial Mutation Test, a Confirmatory Mutation Test and a Complementary Confirmatory Mutation Test. In the Range Finding Test as well as in the Initial Mutation Test, the plate incorporation method was used. In the Confirmatory Mutation Test and Complementary Confirmatory Mutation Test, the pre-incubation method was used. The test substance was found to be non mutagenic under the test conditions used in the study.

In a gene mutation in mammalian cells test, dibromostyrene was tested in the CHO/HGPRT mutation assay at dose levels of 5, 10, 15, 20 and 25 nL/mL in the absence of S9 metabolic activation, and at 25, 40, 55, 60 and 70 nL/mL in the presence of S9 metabolic activation. The test substance was negative, both in the absence and presence of metabolic activation, in this CHO/HGPRT assay.

Cytogenicity:

In an in-vitro unscheduled DNA synthesis, primary hepatocytes cultures were set up from liver of male Sprague-Dawley rats. The top dose of 0.1 µg/mL had a relative toxicity (RT) of 59% and was toxic upon microscopic examination. This dose could not be further evaluated. At the next lower dose of 0.03 µg/mL had a RT of 14% and was also quite toxic, with nuclei somewhat reduced in size, but could be evaluated for unscheduled DNA synthesis. None of the test substance doses caused a significant increase in the mean net grain counts. Dibromostyrene was negative under the conditions of the study.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to the criteria in directive 67/548/EEC and regulation (EC) No 1272/2008, the substance does not meet the criteria for classification concerning mutagenicity as the substance proved to be negative in all the studies provided.