Reaction products of 2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-hydroxyphenol with ((C10-16, rich in C12-13 alkyloxy)methyl)oxyrane

Endpoint summary

Additional information

Performance and observations

There are three reliable, GLP-conform in vitro studies available to assess the potential of the end product for gene mutations in bacteria and clastogenicity in mammalian cells.

The first study was performed to investigate the potential of the test item to induce gene mutations according to the plate incorporation test using the S. typhimurium strains TA1535, TA 1537, TA 98, and TA 100, and the E. coli strain WP2 uvrA (Ciba 1991g). The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the controls, was tested in triplicate. The test item was tested at five concentrations in the range of 312.5 and 5000 µg/plate. No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment at any dose level, neither in the presence nor absence of metabolic activation (S9 mix).

In the second study, test item, dissolved in acetone, was assessed for its potential to induce structural chromosome aberrations in CHO cells in four independent experiments (Ciba 1991h). The experiments differed in test concentration, exposure duration and metabolic activation. 200 metaphases from cultures of two falcon flasks in the vehicle control, in the test groups and 100 metaphases in the positive controls were examined. No clear toxic effects indicated by reduced mitotic indices or reduced cell numbers were observed after treatment with the test item. In all experiments, no biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item. No relevant increase in the frequencies of polyploid metaphases was found after treatment with the test item as compared to the frequencies of the controls.

In the course of the third study, clastogenicity of the test article in cells from Chinese hamster lung (CHL) was determined (Ciba 1994). The test substance, dissolved in acetone, was added at concentrations of 313, 625, 1250, 2500 and 5000 µg/ml for continuous and pulse treatment with and without metabolic activation to the cultures. Mitosis was arrested by adding colcemid (final concentration: 0.2 µg/ml) two hours before the cells harvest. 200 metaphase cells per dose level (100 metaphase cells per slide) were evaluated for assessment of chromosome aberrations. The test substance did not increase the frequency of structural chromosome aberrations and polyploids in both continuous and pulse treatments.

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A structural analogue was tested for mutagenicityin vitroin mammalian cells. Both substances share high similarity in structure, are poorly soluble in water and have a comparable toxicity profile. Moreover, the analogue has a lower molecular weight which gives an additional safety margin.

The mutagenicity assay in mammalien cells (V79) was performed at the following concentrations: 18.52, 55.56, 166.67 and 500 µg/ml in four independent experiments (two with and without metabolic activation). No growth inhibition was found both after treatment and expression. N-Nitrosodimethylamine (DMN, 1.0 µl/ml, without S9 -mix) and ethylmethanesulfonate (EMS, 0.3 µl/ml, with metabolic activation) were used as positive controls. In all experiments comparison of the number of mutant colonies in the controls and in the cultures treated with the various concentrations of the test substance revealed no relevant increase of the mutant frequencies as determined by the screening with 6-Thioguanine (6 -TG). Precipitates of the test substance in the culture medium were visible at the two higher concentrations.

Discussion

In conclusion, it can be stated that under the conditions of the Ames test, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Furthermore, it can be stated that under the experimental conditions reported, the test item did not induce structural chromosome aberrations as determined by the chromosome aberration test in vitro. Incubation of V79 cells with a structural analogue in presence and absence of S9-mix did not induce an increase in mutant frequencies.

Thus, the test substance is not mutagenic and not clastogenic.

Short description of key information:
An Ames test and a chromosome aberration test in V79 and CHL cells was performed according OECD guideline 471 and 473 to evaluate the mutagenic potential of the test substance. The test item did not induce mutations or chromosome aberrations in vitro. An analogue substance was negative for mutagenicity in mammalian cells (OECD 476). Therefore, the substance is considered as non-mutagenic under the conditions of these tests.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for genotoxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for genotoxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).