Tris(p-isocyanatophenyl) thiophosphate

Endpoint summary

Additional information

Tris(p-isocyanatophenyl) thiophosphate is marketed and handled as solution in ethyl acetate containing approximately 27% of tris(p-isocyanatophenyl) thiophosphate. Removal of the solvent from a solution of 27% of tris(p-isocyanatophenyl) thiophosphate in ethyl acetate does invariably lead to generation of higher molecular weight species. This is due to the inherent reactivity of the isocyanate moieties and the process can thus be monitored via the decrease of the isocyanate content (see IUCLID section 1.4: analytical material balances before/after solvent removal). Therefore, a solution of 27% of tris(p-isocyanatophenyl) thiophosphate in ethyl acetate was employed as test substance for all toxicological tests as this was believed to best represent the substance to be registered.

Desmodur RFE was evaluated in an Ames Test on Salmonella typhimurium strains TA 1535, TA 100, TA, 1537, TA 98, and TA 102, performed according to OECD TG 471 up to concentrations of 5000 µg per plate (Herbold, 2002). No biologically relevant increase in the mutant count, in comparison with nevative controls, was observed. Concentrations up to the limit dose did not cause bacteriotoxic effects but the highest tested concentration led to precipitation of the test substance. Thus, the neat tris(p-isocyanatophenyl)thiophosphate was considered to be non-mutagenic without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.

Desmodur RFE was tested in an in vitro gene mutation assay in V79 cells (HPRT) according to OECD TG 476 in concentrations of up to 10 µl/mL with and without metabolic activation (Wollny, 2012).The negative control and appropriate positive controls with known mutagens demonstrated the suitability and sensitivity of the test system. The test item showed no biologically relevant increase in the frequency of mutations in the absence or in the presence of S9 mix. Since up to precipitating concentrations were tested, the neat tris(p-isocyanatophenyl) thiophosphate is considered to be non-mutagenic in the in vitro gene mutation assay.

Desmodur RFE was examined for mutagenic activity (chromsome breakage and misdistribution of chromosomes) in the in vitro micronucleus test using Chinese hamster V79 cells in accordance to OECD TG 487 (Sutter, 2012). The negative control and appropriate positive controls with known mutagens demonstrated the suitability and sensitivity of the test system. The test item showed no biologically relevant increase in the frequency of micronucleus containing V79 cells in the absence (both pulse and continuous treatment) or in the presence of S9 mix (pulse treatment). Since up to precipitating concentrations were tested, the neat tris(p-isocyanatophenyl) thiophosphate is considered to be non-mutagenic in the in vitro micronucleus assay.

In conclusion, tris(p-isocyanatophenyl)thiophosphate did not show mutagenic effects in bacteria and mammalian cells.

Justification for selection of genetic toxicity endpoint
No study was selected since all three in vitro mutagenicity studies were negative.

Short description of key information:
Clearly negative in vitro studies (Ames Test, HPRT Test, Micronucleus Test) performed with and without metabolic activation and tested up to precipitating concentrations.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available study results (negative in Ames test, HPRT test and in vitro Micronucleus test) a classification according to Regulation (EC) No 1272/2008 is not warranted.