Distillates (Fischer-Tropsch), C8-10-branched and linear

Endpoint summary

Additional information

In vitro

The in vitro genotoxicity of a read-across substance (Hydrocarbon, C7 -C9, n-alkanes, isoalkanes, cyclics) has been assessed in different test systems.

A reliable bacterial reverse mutation assay (Ames test) was conducted with this substance following a protocol similar to OECD 471.The pre-incubation procedure was performed with Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100, and Escherichia coli strains WP2 uvr A and WP2.. The strains were exposed to concentrations ranging from 0.31 to 8000 µg/plate for 30 min both with and without metabolic activation prior to plating and further incubation for 48 -72 h.For all strains tested, there was no significant increase in the number of revertants as compared to negative controls. An initial cytotoxicity assay with S. typhimurium TA100 showed that the test substance was extremely cytotoxic, especially in the absence of S9 fraction. Therefore, initial mutation assays were conducted over a low dose range (0.31 -10 µg per mL) with strains TA100 and TA98. Virtually no cytotoxicity was observed at these concentrations, and so more appropriate concentrations were tested for all strains in subsequent assays. Salmonella strains were more sensitive to the cytotoxic effect of the test substance than E. coli strains, and cytotoxicity was greater in the absence of S9-fraction.

In conclusion, the test substance was not mutagenic in this assay (Shell Chemicals, 1983; Brooks et al., 1988).

The potential of hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics to cause chromosomal aberrations in rat liver RL4 cells was tested with a method comparable to OECD 473. Cells were exposed to concentrations of 0, 2.5, 5, and 10 µg/mL of test substance for 22 h, and then examined for chromosomal aberrations including polyploidy, chromatid gaps, and chromatid exchanges. Exposure of RL4 cells to 20 µg/mL test substance resulted in inhibition of cell proliferation by 50%. Therefore 10 µg/mL was chosen as the maximum dose level. No significant increase in the frequency of chromosomal damage was observed. Under the conditions of this study, the test material was not clastogenic (Shell Chemicals, 1983; Brooks et al., 1988).

A gene mutation assay was performed with hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics using yeast cells (similar to OECD 481). Saccharomyces cerevisiae was exposed to concentrations ranging from 0.01 to 5.0 mg/mL both with and without metabolic activation for 18 h and allowed for expression for 3 days. There was no significant increase in the number of revertants or prototrophic colonies as compared to negative controls. Under the conditions of this study the test substance was not mutagenic in either the presence or absence of metabolic activation (Shell Chemicals, 1983; Brooks et al., 1988).

Read across justification is provided in the Read Across Document attached to Section 13.

 

In vivo

A mouse micronucleus assay (comparable to OECD 474) was performed using hydrocarbon, C7 -C9, n-alkanes, isoalkanes, cyclics, administered orally in a single dose of 2000 mg/kg with sampling of bone marrow at 24 and 48 h post-dose. No statistically significant increases in micronucleated polychromatic erythrocytes were observed. The test substance was not clastogenic to mouse bone marrow cells under the conditions of this assay (Fox, 2003).

The in vivo genotoxicity of further structurally similar substances has been tested.

Hydrocarbons, C7-C9, isoalkanes showed no evidence of genotoxicity in a dominant lethal study with rats. Iso-octane did not induce unscheduled DNA synthesis in rat hepatocyte cultures.

Based on this approach, these results from a read-across substance suggest that Distillates (Fischer-Tropsch), C8-C10-branched and linear, are not expected to induce genotoxicity in vivo.

Read across justification is provided in the Read Across Document attached to Section 13.

Justification for selection of genetic toxicity endpoint
The registered substance is negative for genetic toxicity; however, it should be noted that, although the data do not support classification of the registered substance per se for mutagenic potential, there is a regulatory requirement to classify substances containing >0.1% benzene as mutagenic.

Short description of key information:
The available data indicate that Distillates (Fischer-Tropsch), C8-C10-branched and linear, are not genotoxic.
In vitro:
Negative Ames test with S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100, and E. coli WP2 and WP2 uvr A, with and without metabolic activation.
Negative results in mammalian chromosomal aberration test and a mitotic gene conversion assay in yeast, the latter with and without metabolic activation.
In vivo:
Negative in dominant lethal, micronucleus and unscheduled DNA synthesis assays.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on the genotoxic potential of Distillates (Fischer-Tropsch), C8-C10-branched and linear, and structurally related substances are conclusive but not sufficient for classification. However, it should be noted that, although the data do not support classification of the registered substance per se for mutagenic potential, there is a regulatory requirement to classify substances containing >0.1% benzene as mutagenic.