Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Key studies were available for in vitro studies including bacterial reverse mutation, mammalian forward mutation and unscheduled DNA synthesis, as well for in vivo micronucleus testing.

A key study for bacterial mutagenicity was performed with hydrogenated terphenyl in an Ames reverse mutation test with 4 Salmonella thyphimurium strains (TA 1535, TA 1537, TA 98 and TA 100) at test concentration of 0.01, 0.04, 0.2, 1.0, 3.0, 10.0 μL/plate with and without metabolic activation (Kulik & Ross, 1978). A toxic screen was run with the test compound at concentrations of 100.0, 30.0, 10.0, 1.0, 0.3 and 0.1 μL per plate using Salmonella tester strain TA100. In the absence and the presence of metabolic activation, a maximum concentration of 100 μL per plate was tolerated by the bacteria without toxic effects. All strains were tested to be negative for mutagenicity. The study was conducted according to OECD 471 guidelines, and was considered to be reliable, adequate and relevant.

A key study was performed with hydrogenated terphenyl for the cell mutation assay in Chinese hamster Ovary (CHO) cells at 25, 50, 75, 100 and 300 μg/mL with and without metabolic activation (Godek et al., 1985). The study was conducted equivalent to OECD 476 on the hypoxanthine-guanine phosphorybosil transferase (HGPRT) target gene according to GLP guidelines, and was considered to be reliable, adequate and relevant. Cytotoxicity was not observed up to 1000 μg/mL, however precipitation of the test article was apparent in the treatment media at all doses above 100 μg/mL. There were no statistically significant increases in the mutation frequencies of the hydrogenated terphenyl treated cultures when compared to the negative controls at the doses and S-9 concentrations tested.

A key study for DNA damage and/or repair was performed with hydrogenated terphenyl in an in vitro UDS study with primary rat hepatocyte cultures at 0.1, 0.5, 1.0, 5.0, 10.0, 50.0, 100.0, 250.0, 500.0 and 1000.0 μg/mL with and without metabolic activation (Steinmetz and Mirsalis, 1985). The study was conducted according to GLP guidelines, and was considered to be reliable, adequate and relevant. Cytotoxicity was not observed up to 5000 μg/ml. The study was negative.

A key study for in vivo chromosome aberration was performed with hydrogenated terphenyl in the micronucleus assay. The study was conducted according to OECD 475 and GLP guidelines, and was considered to be reliable, adequate and relevant. This study assessed the ability of hydrogenated terphenyl administered by intraperitoneal injection to induce chromosomal damage in bone marrow cells of Fischer-344 rats. In the definitive study, rats were given hydrogenated terphenyl at doses of 0, 250, 1250, and 2500 mg/kg body weight. Groups of animals were sacrificed 6, 12, and 24 hr after treatment. The positive control groups received triethylenemelamine (0.2 mg/kg body weight 1 by intraperitoneal injection and were sacrificed 24 hr after treatment. Cells from animals exposed to 0 and 2500 mg/kg and those from animals in the positive control groups were evaluated microscopically for mitotic index and chromosomal abnormalities. On the basis of the results, it was concluded that hydrogenated terphenyl does not induce chromosomal damage in male or female Fischer-344 rats under the conditions used in this study.

Supporting studies (Klimisch 4) were also available for bacterial reverse mutagenicity and DNA damage and/or repair. A study for bacterial mutagenicity was performed with Terphenyl, hydrogenated in an Ames reverse mutation test with 4 Salmonella thyphimurium strains (TA 1535, TA 1537, TA 98 and TA 100) with and without metabolic activation (Clark et al., 1979). All strains were tested to be negative for mutagenicity up to 10.000 µg/plate with and without metabolic activation. There were no signs of cytotoxicity.A study for DNA damage and/or repair was performed with terphenyl, hydrogenated (NBP2087922) in an in vitro UDS study with primary rat hepatocyte cultures (Monsanto, 1982) .The test was negative.


Short description of key information:
Terphenyl, hydrogenated was studied in vitro for bacterial reverse mutation, mammalian forward mutation and unscheduled DNA synthesis, and in vivo for chromosomal aberration. All studies were negative, demonstrating that there were no indications of genotoxicity.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The endpoint does not meet classification criteria according to EU and/orCLPcriteria.