Distillates (Fischer-Tropsch), heavy, C18-50-branched, cyclic and linear

Endpoint summary

Additional information

The UVCB substance has been tested in a bacterial mutagenicity study according to OECD 471 and under GLP using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and Escherichia coli WP2uvrA. The test material was dissolved in tetrahydrofuran at concentrations up to 5000 µg/plate. Appropriate solvent and positive controls were included and gave expected results. No toxicity to bacterial cells was observed. No significant increase in the number of revertants was observed at any concentration with and without metabolic activation in any of the strains tested. The results were confirmed in a repeat experiment; both experiments used the direct plate incorporation method.An in vitro micronucleus study has been conducted using GTL Base Oil Distillates following OECD draft guideline 487 and conducted under GLP conditions. No increase in the incidence of micronuclei was observed in duplicate cultures of human lymphocytes at any concentration in either the initial experiment (4 hour exposure, 16 hour expression, with and without metabolic activation) or the repeat experiment (20 hour exposure without metabolic activation; 4 hour exposure, 16 hour expression, with metabolic activation). No test material induced toxicity was observed. The test material was dissolved in acetone, and the maximum concentration tested was 2500 µg/plate; higher concentrations could not be tested due to difficulties in formulating the test material in the vehicle. The vehicle controls had frequencies of cells with micronuclei within the range expected for normal human lymphocytes, and appropriate positive controls were concluded and induced significant increases in the number of cells with micronuclei. It was concluded that the test material is non-clastogenic and non-aneugenic to human lymphocytesin vitro.

Further evidence of the lack of effects on chromosomesin vitrowas obtained when the substance was tested according to OECD 473 and under GLP. No statistically significant increase in the frequency of cells with chromosome aberrations was observed in either the initial or the repeat experiment when tested with and without metabolic activation up to a dose level that was limited by the onset of precipitate. Appropriate solvent and positive controls were included and gave expected results.

Moreover, in vivo data is available from an in vivo chromosome aberration study on the substance, conducted according to OECD 475 and under GLP:

The test was conducted using the oral route in groups of seven rats at the maximum recommended dose (MRD) 2000 mg/kg for the 24-hour and 48-hour time points, with 1000 and 500 mg/kg as the lower dose levels. Animals were killed 24 or 48 hours later, the bone marrow was extracted, processed and slide preparations made and stained. Bone marrow cells were scored for the presence of chromosome aberrations.

There were no premature deaths seen in any of the test item dose groups. No clinical signs were observed in animals dosed with the test item at any dose level.No marked decreases in the mitotic index mean value were observed in any of the test item dose groups when compared to the vehicle control group.

There was no evidence of a statistically significant increase in the incidence of cells with chromosome aberrations excluding gaps in animals dosed with the test item, when the dose groups were compared to the vehicle control group. 

The test item did not induce any statistically significant increases in the numbers of polyploid cells at any dose level in any of the exposure groups and it did not induce any significant or dose-related increases in the frequency of chromosome aberrations. The test item was considered to be non-clastogenic to rat bone marrow cells in vivo.

Short description of key information:
In vitro:
- Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains (TA 98, 100, 1535, 1537) and Escherichia coli WP2uvrA (OECD 471).
- Cytogenicity in mammalian cells: negative with and without activation in human lymphocytes (OECD Draft Guideline 487).
- Cytogenicity in mammalian cells: negative with and without activation in human lymphocytes (OECD 473).

In vivo:
Cytogenicity: negative in Mammalian Bone Marrow Chromosome Aberration Test (OECD 474/EU B.11)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo data the substance is not genotoxic and does not require classification according to Regulation 1272/2008/EC.