Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro Gene Mutation study in Bacteria AMES OECD471:

Negative in the absence and presence of S9 metabolism.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Studies on bacteria (AMES)

The study was performed to investigate the potential of test item to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, and TA 100 on the Similar substance 01.

No toxic effects, evident as a reduction in the number of revertants, occurred in the test groups with and without metabolic activation. The plates incubated with the test article showed normal background growth up to 5000 μg/plate with and without S9 mix in all strains used. No relevant increase in revertant colony numbers of any of the four 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 conclusion, under the experimental conditions reported, the test article did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.

Therefore, test item is considered to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.

Based on the read-across principle(read-across from supporting substance -structural analogue or surrogate), this result can be considered for the genetic toxicity assessment of the registered substance.

Justification for read-across is detailed in the report attached to the IUCLID section 13.

Justification for classification or non-classification

This hazard class is primarily concerned with substances that may cause mutations in the germ cells of humans that can be transmitted to the progeny.

Substance that are mutagenic in somatic cells may produce heritable effects if they, or their active metabolites, have the ability to interact with the genetic material of germ cells. Conversely, substances that do not induce mutations in somatic cell in vivo would not be expected to be germ cell mutagens.

However, the results from mutagenicity or genotoxicity tests in vitro and in mammalian somatic and germ cells in vivo are also considered in classifying substances and mixtures within this hazard class.

Category 1: substances known to induce heritable mutations or to be regarded as if they induce heritable mutations in the germ cells of humans. Substances known to induce heritable mutations in the germ cells of humans.

Category 2: substances which cause concern for humans owing to the possibility that they may induce heritable mutations in the germ cells of humans.

Classification for heritable effects in human germ cells is made on the basis of well conducted, sufficiently validated tests as In vitro mutagenicity tests such as these indicated in 3.5.2.3.8:

- in vitro mammalian chromosome aberration test;

- in vitro mammalian cell gene mutation test;

- bacterial reverse mutation tests

Under the experimental conditions reported, the test article did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.

As conclusion, according to the CLP Regulation n.1272/2008 and the ECHA Guidance R.7a, the substance should be considered non mutagenic, and not classified for the genetic toxicity.