1-isoctyloxycarbonyl ethylated 2,4,6 tris (2,4- hydroxyphenyl) -1,3,5 triazine derivatives

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 cytogenicity in mammalian cells.

The first study (CIBA 2002d) was performed to investigate the potential of the test item to induce gene mutations according to the plate incorporation test (experiment I) and the preincubation test (experiment II) using the S. typhimurium strains TA1535, TA 1537, TA 98, and TA 100, and the E. coli strain WP2 uvrA. 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 the following concentrations: 33; 100; 333; 1000; 2500; and 5000 µg/plate. Minor toxic effects (below the factor of 0.5), evident as a reduction in the number of revertants, were observed in strain TA 1535 at 1000 and 5000 µg/plate with metabolic activation and in strain TA 1537 at 2500 and 5000 pg/plate with and without metabolic activation in experiment I. In experiment II, a minor toxic effect was also observed in strain TA 98 at 5000 µg/plate with metabolic activation. 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). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

 

In the second study (CIBA 2002), test item, dissolved in acetone, was assessed for its potential to induce structural chromosome aberrations in V79 cells of the Chinese hamster in vitro in two independent experiments. In each experimental group two parallel cultures were set up. Per culture 100 metaphase plates were scored for structural chromosome aberrations. The highest applied concentration in the pre-test on toxicity (5000 µg/ml) was chosen with respect to the current OECD Guideline 473. Since no relevant toxicity was observed in the pre-test on toxicity, the test item was tested up to a concentration exhibiting clear test item precipitation as recommended in the OECD Guideline 473. No clear toxic effects indicated by reduced mitotic indices or reduced cell numbers were observed after treatment with the test item. In both independent 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.

At last, an HPRT assay in V79 cells was conducted to to investigate the potential of the test item to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster. The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours.The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation.

The highest concentration of the pre-experiment and the main experiments (3600 µg/mL) was limited by the solubility properties of the test item. The test item was dissolved in acetone. No substantial and reproducible dose dependent increase of the mutation frequency was observed up to the maximum concentration with and without metabolic activation.

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 V79 cells in vitro. At last, it can be stated that the test item did not induce gene mutations at the HPRT locus in V79 cells. Thus, the test substance is not mutagenic and not clastogenic.

Short description of key information:
An Ames test, an HPRT assay and a chromosome aberration test in V79 cells was performed according OECD guideline 471, 476 and 473 to evaluate the genotoxic potential of the test substance. The test item did not induce mutations or chromosome aberrations in vitro. Therefore, the substance is considered as non-genotoxic 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 30th time in Directive 2008/58/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).