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Key value for chemical safety assessment

Genetic toxicity in vitro

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No data are available for for Tetraethylhexyl titanate itself. Rapid hydrolyses into 2 -Ethyl hexanol and Titanium dioxide is expected after ingestion into the body.

2-Ethyl hexanol is rapidly and extensively absorbed via the gastrointestinal tract in rats and rabbit.

2 -Ethylhexanol was evaluated in OECD SID Programme in 1995. Only short summary of the conclusions and reccomendations is available:

2EH was negative in Salmonella mutagenicity tests and chromosomal aberration tests (in vitro and in vivo). Other studies indicate that 2EH does not have genotoxic activity and carcinogenic potential was not demonstrated in studies in rats and mice. NOAELrat = 50mg/kg.

In an Ames test [OECD TG 471] with multiple strains of Salmonella typhimurium, and one strain of Escherichia coli, titanium dioxide did not induce gene mutations in vitro with and without metabolic activation. In a mammalian cell gene mutation assay [OECD TG 476] with mouse lymphoma L5178Y TK +/- cells, titanium dioxide was not mutagenic both with and without metabolic activation. Titanium dioxide did not induce chromosomal aberrations [OECD TG 473] in in vitro Chinese Hamster Ovary (CHO) cells and human lymphocytes with and without metabolic activation. In in vitro sister chromatid exchange (SCE) assays, titanium dioxide induced increasing SCE frequencies in CHO-K1 cells and human lymphocytes but did not induce any effects of SCE in CHO cells. In CHO-K5 cells, titanium dioxide did not induce micronucluses but induced it in CHO-K1 cells and human lymphocytes.

In a recombination assay with Bacillus subtilis H17 (rec+) and M45 (rec-), titanium dioxide showed a negative result.

In an in vivo study [no guideline followed], titanium dioxide did not induce chromosome aberrations in mouse bone marrow cells and did not significantly elevate levels of micronuclei in the bone marrow cells of mice. However, it is not clear whether there was any exposure of the target tissues. In an in vivo sex-linked recessive lethal (SLRL) test with Drosophila melanogaster, it was suggested that titanium dioxide showed a negative result. In a non-standard hprt gene mutation assay, the hprt mutation frequency was significantly increased in alveolar type II cells of rats after in vivo exposure to titanium dioxide. Based on the results from mutagenicity studies in vitro, the majority of the studies were negative (Ames, chromosome aberration and mammalian cell gene mutation tests).

Positive results with titanium dioxide were observed in two micronucleus studies and two Sister Chromatid Exchange assays in vitro and were thought to be a consequence of oxidative stress mediated DNA damage. In vivo the results of somatic cell studies were negative, however it is not possible to conclude on the in vivo genotoxic potential of titanium dioxide due to a positive result observed in a non-standard in vivo site of contact study in alveolar cells.

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