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

Negative. The substance is not mutagenic for bacteria

In vitro mammalian cells Micronucleus test, OECD487

Negative. The substance is not mutagenic for mouse lymphoma.

In vitro mammalian cell gene mutation assay, OECD476

Negative. The substance is not mutagenic for mammalian cells.

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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

For substances covered by Annex VIII to REACH genetic toxicity on bacteria and two tests on in vitro mammalian cells are required.

The tests required to fulfil the ANNEX VIII were performed on a similar substance 01 (read-across from supporting substance -structural analogue or surrogate).

Based on the read-across principle, this evaluated conclusion can be considered valid for the genetic toxicity assessment of the registered substance. Justification for Read Across is detailed in the report attached to the IUCLID section 13.

Studies on bacteria (AMES)

TodeschiniQSAR mutagenicity AMES test (v. 2.0)prediction on the Constituent 1 resulted negative.

The mutagenicity on bacteria was performed following the OECD 471 on Similar substance 01. Both test resulted negative for bacteria.

Studies on in vitro

The Similar substance 01 did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation OECD476, in GLP.

preliminary toxicity tests didn’t show cytotoxicity, toxicity was detected at 6000 µg/mL in the second experiment after 24 hours of exposure with metabolic activation. The experiments resulted on negative results (no adverse effect observed).

Therefore, the substance is considered to be non-mutagenic in this mouse lymphoma assay.

The Similar substance 01 did not induce mutation in the in vitro Micronucleus Test in Chinese Hamster V79 cells (met. act.: with and without) (OECD Guideline 487 and GLP). Preliminary toxicity tests showed cytotoxicity at 1470.5 µg/mL and above. The result of the study is that the substance is considered to be non-mutagenic in this in vitro test system, when tested up to the highest evaluable and/or precipitating concentrations.

The substance is considered to be non-mutagenic in this in vitro test system micronucleus assay, when tested up to the highest evaluable and/or precipitating concentrations.

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

The Similar substance 01 did not induced gene mutations in the strains in the Salmonella typhimurium reverse mutation assay.

However, additional studies are available for the mutagenicity in vitro on mammalial cells (OECD476 and OECD487), resulted negative.

Based on the read-across principle, the available results are considered for the genetic toxicity assessment of the substance.

As conclusion, according to the CLP Regulation n.1272/2008 and the ECHA Guidance R.7a, the substance is not classified as mutagenic.