Benzene, C15-16-alkyl derivs.

Endpoint summary

Additional information

In cases where no data were available on the target substance, Benzene, C15-16-alkyl derivs., data were read across from a structurally related material (the test substance).

In vitro studies:

There are four key studies that examine the potential for mutagenicity of read-across source substances for Benzene, C15-16-alkyl derivs., using several in vitro methods. In the first key study (Robinson and Nair 1992), Salmonella typhimurium strains TA 1535, TA 100, TA 1537, and TA 98 were exposed to test substance concentrations of 10, 40, 200, 1000, 3000 and 10,000 µg/plate. DMSO was used as a solvent. The positive controls used were 9-aminoacridine, sodium nitrite, benzo(a)pyrene, 2-acetylaminofluorene, and 2-nitrofluorene. No reproducible, dose-response related positive results were seen in the treatment groups and therefore the results were considered negative both with and without activation. A significant increase in revertants per plate was seen in the positive controls, demonstrating the validity of the test. Therefore, the test substance is not mutagenic.

The second key study (Robinson and Nair 1992) determined the mutagenicity of the test substance. Salmonella typhimurium strains TA 1535, TA 100, TA 1537, and TA 98 were exposed to concentrations of 3, 12, 60, 300, 1000, and 3000 µg/plate of test substance. DMSO was used as a solvent. The positive controls used were 2-acetylaminofluorene, 9-aminoacridine, 4-nitroquinoline-N-oxide, sodium nitrite, and benzo(a)pyrene. No positive results were seen in the treatment groups. The results were considered negative with and without activation. The expected increase in revertants per plate was seen in the positive controls. The test substance is not mutagenic.

The third key study (Robinson and Nair 1992a) examined the potential of the test substance to cause mutations in mammalian cells. Chinese hamster ovary cells were exposed to 11 concentrations ranging from 100 to 2000 µL/mL of test substance both in the presence and absence of metabolic activation. Ethanol was used as a vehicle. Ethylmethanesulfonate, benzo(a)pyrene, and dimethylnitrosamine were used as positive controls. Cytotoxicity was seen at concentrations of 1000 µg/mL and above with metabolic activation and 250 µg/mL and above without metabolic activation. No significant increase in mutation frequencies was seen in treatment groups. The test substance is not mutagenic to mammalian cells.

The fourth key study (Robinson and Nair 1992b) examined the potential of the test substance to cause mutations in mammalian cells. Again, Chinese hamster ovary cells were exposed to 11 concentrations ranging from 100 to 2000 µL/mL of test substance both in the presence and absence of metabolic activation. Ethanol was used as a vehicle. Ethylmethanesulfonate, benzo(a)pyrene, and dimethylnitrosamine were used as positive controls. Cytotoxicity was seen at concentrations of 500 µL/mL and above both with and without metabolic activation. No significant increase in mutation frequencies was seen in treatment groups. The test substance is not mutagenic to mammalian cells.

In vivo studies:

The first key study (Robinson and Nair 1992a) examined the potential of the test substance to cause chromosome aberrations in vivo. Groups of 18-24 male and female rats were given doses of 2000, 6000, or 12,700 mg/kg of test substance. Negative control animals were given corn oil (vehicle) only. Positive control animals were given 40 mg/kg cyclophosphamide. Animals were sacrificed at 6, 12, 24, and 48 hrs after exposure. The bone marrow cells were then removed and examined for chromosome aberrations. There was significant mean body weight loss in animals treated with 12,700 mg/kg bw in both males and females. Males in the 6000 mg/kg dose level also showed weight loss. However, no significant increase in chromosomal aberrations was seen in any treatment group. Therefore, the test substance is not clastogenic.

The second key study (Robinson and Nair 1992b) examined the potential of the test substance to cause chromosome aberrations in vivo. Groups of 18-24 male and female rats were given doses of 1200, 4000, or 12,700 mg/kg of test substance. Negative control animals were given corn oil (vehicle) only. Positive control animals were given 40 mg/kg cyclophosphamide. Animals were sacrificed at 6, 12, 24, and 48 hrs after exposure. The bone marrow cells were then removed and examined for chromosome aberrations. Significant mean body weight loss occurred only at the 12,700 mg/kg dose in both males and females. No significant increase in chromosomal aberrations was seen in any treatment group. The test substance is not clastogenic .

In the third of three key studies (Kuhnert 1989), groups of 15 female and 15 male mice were given a single dose of the test substance to determine the effect on bone marrow erythrocyte production. Five animals of each sex were sacrificed at 24, 48, and 72 hrs after exposure. Similar groups were exposed to cyclophosphamide (positive control), and water (negative control). All animals in the positive control group were sacrificed at 24 hours. Animals in the treatment group exhibited diarrhea and diuresis during the treatment period. There was a significant increase in the polychromatid erythrocytes/normochromatid erythrocytes ratio and PCE cells with micronucleus in the positive control group. There was no significant increase in either of these parameters in the treatment group. Analysis of the bone marrow showed no significant increase in either micronucleus or PCE in the treatment group as compared to negative controls. Therefore, the test substance is not clastogenic.

Short description of key information:
Four in vitro and three in vivo studies of read-across source substances for Benzene, C15-16-alkyl derivs. support the conclusion that the registered substance is neither mutagenic nor clastogenic.

Endpoint Conclusion: No adverse effect observed (negative)