1-Propanol, 2-methyl-3-[(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)oxy]-

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

- Gene Mutation in Bacteria (Bacterial Reverse Mutation Assay/Ames): negative with and without metabolic activation (OECD TG 471)

- In vitro chromosomal aberration test: negative with and without metabolic activation (OECD TG 473)

- In vitro mouse lymphoma assay: negative with and without metabolic activation (OECD TG 476)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Ames test:

In the Ames test performed according to OECD 471 histidine dependent auxotrophic mutants of Salmonella typhimurium (strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100) and a tryptophan dependent mutant of Escherichia coli (WP2uvrA) were exposed to the test material, diluted in dimethyl sulphoxide which was also used as a negative control. Two independent mutation tests were performed, in the presence and absence of liver preparations from Aroclor 1254-induced rats. In the preliminary dose range finding study with dose levels of up to 5000 µg/plate toxicity was observed towards all the tester strains at the top dose level. A top dose level of 5000 µg/plate was chosen for the subsequent mutation study. To ensure that sufficient non-toxic dose levels were tested other dose levels used in the first mutation assay were: 2500, 1250, 625, 312.5, 156.25, 78.125 and 39.0625 µg/plate. In the first mutation assay some toxicity was observed down to 312.5 µg/plate so an additional lower dose level of 19.53125 µg/plate was included in the second mutation assay. Results: No evidence of mutagenic activity was seen at any dose level of Bornafix in either mutation test. The concurrent positive control compounds demonstrated the sensitivity of the assay and the metabolising activity of the liver preparations. It is concluded that, when tested in dimethyl sulphoxide, Bornafix was not mutagenic in this bacterial system.

In vitro chromosomal aberration test:

A study was performed to assess the ability of Bornafix to induce chromosomal aberrations in human lymphocytes cultured in vitro. Cultured human lymphocytes, stimulated to divide by addition of phytohaemaglutinin, were exposed to the test substance both in the presence and absence of S-9 mix derived from rat livers. Solvent and positive control cultures were also prepared. Cells were harvested 18 and 32 hours after initiation of treatment. Prior to the harvest cell division was arrested in metaphase using colchicine. The cells were then treated with a hypotonic solution, fixed and stained, so that metaphase figures could be examined for chromosomal damage. In order to assess the toxicity of Bornafix to cultured human lymphocytes the mitotic index of all cultures treated with the test substance and the solvent control was calculated. On the basis of these data the dose levels were selected for the metaphase analysis. In the absence of S-9 mix, 31.3, 15. 6 and 3.9 µg/ml of Bornafix were chosen for the 18 hour harvest and 15. 6, 7.8 and 20 µg/ml for the 32 hour harvest. In the presence of S-9 mix, the dose levels chosen for the earlier harvest were 60, 30 and 10 µg/ml and for the later harvest were 25, 15 and 3.8 µg/ml. Results: In both the absence and presence of S-9 mix, at 18 and 32 hour sampling times, Bornafix caused no substantial increases in the proportion of metaphase figures containing chromosomal aberrations at any dose level when compared with the solvent control. Although there were statistically significant increases observed in the presence of S-9 mix, 18 and 32 hour harvests, the increases lie well within the historical control range. In addition, the mean frequencies of aberrant cells in the solvent control cultures were relatively low when compared with the mean historical control values. Both positive control compounds caused large statistically significant increases in the number of aberrant cells. It is concluded that Bornafix has shown no evidence of clastogenic activity in this in vitro cytogenetic test system.

In vitro mouse lymphoma assay:

The effects of Bornafix on the induction of forward mutations at the thymidine-kinase locus (TK-locus) in L5178Y mouse lymphoma cells were studied in a test according to OECD 476. The test was performed in two independent experiments in the absence and presence of S9-mix (rat liver S9-mix induced by a combination of phenobarbital and ß-naphthoflavone). Results: The spontaneous mutation frequencies in the solvent-treated control cultures were between the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay, except the response in the presence of S9-mix (first experiment) and in the absence of S9-mix (second experiment). However, since these mutation frequencies were just below the lower limit of the range and clear negative results were obtained, the validity of the test was considered to be not affected. Mutation frequencies in cultures treated with positive control chemicals were increased by 10-fold for MMS in the absence of S9-mix, and by 23- and 13-fold for CP in the presence of S9-mix. It was therefore concluded that the test conditions, both in the absence and presence of S9-mix, were appropriate and that the metabolic activation system (S9-mix) functioned properly. In the absence of S9-mix, Bornafix did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the duration of treatment time. In the presence of S9-mix, Bornafix did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the concentration of the S9 for metabolic activation. In conclusion, Bornafix is not mutagenic in the TK mutation test system under the experimental conditions of the test.

Justification for classification or non-classification

Based on the available information, the substance is not genotoxic and therefore does not have to be classified for genotoxicity in accordance with EU CLP (EC no. 1272/2008 and its amendments).