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Administrative data

Key value for chemical safety assessment

Additional information

Genetic toxicity in vitro

A Salmonella/microsome plate incorporation test was performed according to the OECD TG 471 (Bayer, 2007). Reverse mutations were assessed in the Salmonella typhimurium strains tester TA 1535, TA 100, TA 1537, TA 98 and TA 102. Initially, doses up to and including 5000 µg per plate were tested, but due to the observed cytotoxicity, an independent repeat was performed as preincubation assay using doses up to and including 128 µg/plate. Both assays were performed in absence and in presence of metabolic activation (S9 -mix). No evidence of mutagenic activity of the test substance was seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed. In contrast and as expected, the positive controls had a marked mutagenic effect. Thus, Hexamethylene diisocyanate, oligomers (biuret) was not mutagenic in this Ames Test.

 

This result is consistent with another independent OECD Guideline 471 Bacterial Reverse Mutation Assay (Bushy RCC, 1991). The test concentrations for the main mutagenicity test were chosen from data obtained in a preliminary cytotoxicity study with strain TA100. Following test concentrations were chosen: 0.001, 0.003, 0.01, 0.03, 0.1 mg/plate without S9 mix and 0.01, 0.03, 0.1, 0.3, 1 mg/plate with S9 mix. Repetitive test performance revealed no mutagenic activity of the test substance in the absence or in the presence of S9 mix in all tested strains (S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100). No E.coli or S. typhimurium TA 102 was included in the assay. Thus the test item is not considered mutagenic in bacteria under the test conditions used.

 

Hexamethylene diisocyanate, oligomers (biuret) was evaluated for cell gene mutation in the HGPRT forward mutation assay in CHO cells (Bushy RCC, 1992). Test performance was in principle similar to the OECD TG 476. Based on the results of preliminary cytotoxicity studies, CHO ce1ls were treated in the main assay with five concentrations ranging from 0.003 to 0.10 mg/mL in the absence of S9 mix and from 0.01 to 0.30 mg/mL in the presence of S9 mix. No biologically significant indication for a mutagenic potential of the test substance was identified, and the test item was not considered mutagenic to CHO cells either in the absence or in the presence of S9 mix under the test conditions used.

 

An in vitro chromosomal aberration assay was performed with Chinese Hamster Ovary cells (Bushy RCC, 1992). Test performance was in agreement to the OECD TG 473. Based on the results of preliminary cytotoxicity studies, CHO ce1ls were treated in the main assay with five concentrations ranging from 0.00003; 0.0001; 0.0003; 0.001; 0.003 mg/mL in absence of S9 mix and 0.003; 0.01; 0.03; 0.05; 0.1 mg/mL in presence of S9 mix. A treatment of cultured CHO cells with the test item for 4h did not result in statistically significant or dose-related increases in the frequencies of chromosomal aberrations in the absence or in the presence of S9 mix. Therefore, the test item indicated no genotoxic (clastogenic) properties with the defined test conditions.


Short description of key information:
2 negative in vitro gene mutation assays in bacteria (Ames assays).
Negative in vitro cytogenicity assay in mammalian cells (chromosomal aberration/CHO).
Negative in vitro gene-mutation assay in mammalian cells (HPRT/CHO).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Dangerous substance Directive (67/548/EEC)

Based on the criteria of Directive 67/548/EEC, as amended for the 28thtime in Directive 2001/59/EC classification for genetic toxicity is not warranted.

 

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

Based on the criteria laid down in Regulation (EC) No. 1272/2008, as amended for the 2ndtime in Directive EC 286/2011, classification for genetic toxicity is not warranted.