Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the results of the read across in vitro genotoxicity studies, the test substance is not considered to be genotoxic. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Study 1: A study was conducted to determine the mutagenic potential of read across substance, Coco TMAC (33% active in water), according to OECD 471 and EPA OPPTS 870.5265 Guidelines, in compliance with GLP. Using pour-plate assays, the read across substance was examined for mutagenic activity in four strains of Salmonella typhimurium: TA 100, TA 1535, TA 1537 and TA 98 in the absence and in the presence of S9-mix. The test concentrations included 0, 1, 3, 10, 32 and 100 µg/plate (i.e., equivalent to 0, 0.33, 0.99, 3.3, 10.56 and 33 µg/plate). No increase in reversion to prototrophy was obtained with any of the bacterial strain at any concentration level either in the presence or absence of S9-mix. Further, inhibition of growth, observed as thinning of the background lawn of non-revertant cells, occurred in all strains following exposure to the read across substance at 100 µg/plate.Appropriate positive control chemicals (with S-9 mix where required) induced marked increases in revertant colony numbers with all strains, confirming sensitivity of the cultures and activity of the S-9 mix. Under the study conditions, the read across substance was not mutagenic with and without metabolic activation (May, 1989).

Study 2: A study was conducted to determine the clastogenic potential of the read across substance, Coco TMAC (33% active), in cultured human lymphocytes according to OECD Guideline 473, in compliance with GLP. After a concentration range finding test, two independent tests were performed in cultured peripheral human lymphocytes in the presence and absence of a metabolic activation system (S9-mix). With S9-mix cells were exposed for 24 hours. The read across substance produced a reduction in mitotic activity (i.e., approximately 48%) at 10 µg/L in the absence of S9-mix and at 10 (i.e., 20%) and 50 (i.e., 37%) µg/L in the presence of S9-mix. Further, consideration of mean aberrant cell frequencies showed no real increases in culture tested with the read across substance, when compared to control. Statistical analysis confirmed these observations. However, there was an apparent increase in the number of polyploid cells, compared to concurrent control values in all tested cultures, although a marked effect was seen only in activated cultures exposed to 50 µg/mL the author concluded that the read across substance is not clastogenic in human lymphocytes under the experimental conditions. Under the study conditions, the read across substance was not found to be clastrogenic in human lymphocytes (Richardson, 1989).

Study 3: A study was conducted to determine the potential of the read across substance, Coco TMAC (35.5% active in water), to induce mutations at the TK (thymidine kinase) locus in L5178Y mouse lymphoma cells. Study was performed accoding to OECD 476 Guideline, EU Method B.17 and Commission directive 2002/32/EC and U.K Environmental Mutagen Society, in compliance with GLP. After a preliminary toxicity test, 0.625, 1.25, 2.5, 5, 10 and 20 µg/L was selected as the test concentrations for the first experiment. The experiment was repeated to confirm the results of the first experiment. Three hour exposures were used both with and without S9-mix while for the second experiment, the exposure time was increased to 24 h. For the second experiment, the concentration range was 2.5 to 30 µg/L with S9-mix and 0.313 to 5 µg/L without S9-mix. The read across substance did not induce a statistically significant or concentration-related increase in the mutant frequency at any concentration level, either with or without metabolic activation. Adequate levels of toxicity were achieved in all exposure groups. Under the study conditions, the read across substance was not found to show mutagenic activity in mouse lymphoma assay (Nolan, 2002).

Justification for classification or non-classification

Based on the available negative results from read across in vitro genotoxicity assays, the test substance does not warrant a classification for genotoxicity according to EU CLP criteria (Regulation EC 1272/2008).