Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

Mutagenic activity of the test item was investigated in Salmonella typhimurium strains TA 1535, TA 97a, TA98 and TA100 as well as Escherichia coli strain WP2 uvrA with (induced rat liver S9 mix) and without metabolic activation at concentrations of 0, 10, 50, 100, 500, 1000, 2500 and 5000 µg/plate using the plate incorporation assay.

The test item did not reveal any mutagenic activity under the conditions tested. The appropriate reference mutagenes showed distinct positive mutagenic effects.

In another guideline study (according to OECD 471) with different strains of Salmonelle typhimurium (TA 1535, TA 97, TA 98, TA 100) different concentrations of test substance were tested for their mutagenic potential (0, 33,100,333,1000,1666 µg/plate, in any case the substance was tested up to at least slightly toxic concentrations; in certain cases 3333 and 6666 µg/plate were tested too). The test item showed no mutagenic activity in a plate incorporation assay with and without metabolic activation.

The test item, suspended in RPMI medium, was assessed for its potential toinduce structural chromosome aberrations in human lymphocytes two independent experiments. The following study design was performed:

 

Without S9 mix

With S9 mix

 

Exp. I

Exp. II

Exp. I

Exp. II

Exposure period

 3 hrs

24 or 48 hrs

 3hrs

 3hrs

fixation time

24 hrs

24 or 48hrs

24 hrs

48 hrs

In the first cytogenetic assay, the test substance was tested up to 992 µg/ml (0.01 M) for a 3 h exposure time with a 24 h fixation time in the absence and presence of 1.8% (v/v) S9- fraction.

In the second cytogenetic assay, the test substance was tested up to 350 µg/ml for a 24 h continuous exposure time with a 24 h fixation time and up to 400 µg/ml for a 48 h continuous exposure time with a 48 h fixation time in the absence of S9-mix. Appropriate toxicity was reached at these dose levels. In the presence of S9-mix the test substance was tested up to 992 µg/ml (0.01 M) for a 3 h exposure time with a 48 h fixation time.

In each experimental group two parallel cultures were set up. At least 1000 metaphases per culture were evaluated for structural chromosome aberrations.

Appropriate mutagens were used as positive controls. They induced statistically significantincreases (p < 0.05) in cells with structural chromosome aberrations.

It was concluded that the test substance is not clastogenic in human lymphocytes under the experimental conditions described in the report.

Short description of key information:

The genotoxic potential of the submission substance has been assessed in three studies,

- including a bacterial reverse mutation assay (Salmonella typhimurium strains TA 1535, TA 97a, TA 98 and TA 100 and Escherichia coli WP2 uvr A; according to OECD test guideline 471; GLP),

- a second bacterial reverse mutation assay (S. tphimurium strains TA 1535, TA 97, TA 98 and TA 100; similar to OECD test guideline 471), and

- a mammalian chromosome aberration test (in vitro peripheral human lymphocytes; according to OECD test guideline 473; GLP).

In all studies negative results were reported in the presence and absence of metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In a reliable set of bacterial mutation assays and an in vitro chromosomal aberration test the test item is considered to be non-mutagenic and is not a clastogenic agent.

Based on the available data no classification according to Regulation (EC) No. 1272/2008 and Council Directive 67/548/EEC on mutagenicity is warranted.