1,4:5,8-Dimethanonaphthalene, 2-ethylidene-1,2,3,4,4a,5,8,8a-octahydro-

Endpoint summary

Additional information

A bacterial reverse mutation test was conducted (Kashima Laboratory, Mitsubishi-Kasei Institute of Toxicological and Environmental Sciences, 1989) according to official Japanese test guidelines, and in compliance with GLP. Strains of Salmonella Typhimurium (TA98, TA100, TA1535, and TA1537) and E. Coli (WP2 uvrA) were treated with increasing concentrations of ETD by the preincubation method, with and without metabolic activation (S9 Mix). The S. Typhimurium strains were tested up to the point of cytoxicity, and the E. Coli strain up to the point of precipitation. Treatment with the test material did not induce any increase in the number of revertant colonies relative to the concurrent solvent controls, and no the test material was concluded not to have shown any mutagenic potential in this test.

 

A chromosomal aberration study was conducted (Kashima Laboratory, Mitsubishi-Kasei Institute of Toxicological and Environmental Sciences, 1989) according to official Japanese test guidelines, and in compliance with GLP. Chinese hamster lung fibroblast cells were treated with ETD with and without metabolic activation (S9 Mix), and then the subsequent incidence of chromosomal aberrations was determined and compared against concurrent solvent control samples. The incidence of cells with aberrant chromosomes did not increase significantly in any of the treatment groups relative to the controls, and therefore the test was concluded to have been negative; ETD did not display mutagenic potential in this test.

 

An In-vivo Mammalian Cell Gene mutation study was conducted (RCC Cytotest Cell Research GMBH, 1999) according to OECD test guideline 476 and EEC directive 87/302, and in compliance with GLP. Mouse Lymphoma L5178Y cells were treated with ETD a increasing concentrations, with and without metabolic activation. Under the experimental conditions, the test item induced mutations in the mouse lymphoma thimidine kinase locus assay using the cell line L5178Y at highly toxic concentrations following continuous treatment for 24 hours.

Short description of key information:
Bacterial reverse mutation (S Typhimurium TA98, TA100, TA1535, and TA1537, and E Coli WP2 uvrA); no mutagenic activity, with and without metabolic activation.

Chromosome aberration, Chinese Hamster Lung Fibroblasts: No mutagenic potential, with or without metabolic activation.

Mammalian cell gene mutation: Mouse lymphoma L5178Y cells assay: Mutations seen at highly toxic concentrations.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

No mutagenic activity was observed in either a bacterial reverse muation (Ames) test or the chromosomal aberration test conducted in mammalian cells in vitro, however an in-vitro gene mutation study in mammalian cells (Mouse lymphoma L5178Y cells) did present mutagenic activity when tested at cytotoxic concentrations. Whilst it may be reasonable to propose that the mutagenic activity seen in the gene mutation test is a result of the cytotoxic activity, the mutagenic potential of ETD cannot be discounted without additional, higher-tier testing (typically in-vivo testing), and so ETD must be considered mutagenic.

According to EC Regulation 1272/2008, ETD is classified as Mutagenic, category 2; the associated Hazard phrase is "H341: Suspected of causing genetic defects". The corresponding classification under the Dangerous Substances Directive (67/548/EEC) is: Mutagen category 3, "R68, Possible risk of irreversible effects".