Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

AMES plate incorporation: negative

AMES pre-incubation: negative

Hprt: negative

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

Genetic toxicity in vivo

Description of key information

micronucleus test: negative

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

Additional information

IN VITRO BACTERIAL CELL REVERSE MUTATION ASSAY

The potential of the test item to induce point mutations by base pair changes or frameshifts was evaluated in two experimental studies according to the OECD Guideline 471 (1983) and the EU Method B.14 (1984): one according to the plate incorporation method and the other according to the pre-incubation method, a method specific for azo dyes such as this test item.

IN VITRO MAMMALIAN CELL GENE MUTATION ASSAY

The potential for mutagenic activity of the test item was assessed in an experimental study according to the OECD Guideline 476 (2016).

IN VIVO MAMMALIAN CELL MICRONUCLEUS ASSAY

Potential to induce micronuclei in polychromatic erythrocytes in the femoral bone marrow of the mouse was evaluated in an in vivo experimental study according to the OECD Guideline 474 (1983).

Justification for classification or non-classification

According to the CLP Regulation (EC) no. 1272/2008, the term ‘mutation’ refers a permanent change in the amount or structure of the genetic material in a cell, both to heritable genetic changes that may be manifestedat the phenotypic level and to the underlying DNA modifications when known (including specific base pair changes and chromosomal translocations). The terms ‘mutagenic’ and ‘mutagen’ are used for agents giving rise to an increased occurrence of mutations in populations of cells and/or organisms. For the purpose of the classification for germ cell mutagenicity, substances may be allocated to one of two categories:

-Category 1: substances known to induce heritable mutations or to be regarded as if they induce heritable mutations in the germ cells of humans or substances known to induce heritable mutations in the germ cells of humans. Further sub-classification can be made into the following:

-Sub-category 1A: in the presence of positive evidence from human epidemiological studies; or

-Sub-category 1B: in the presence of positive result(s) from (i) in vivo heritable germ cell mutagenicity tests in mammals; (ii) in vivo somatic cell mutagenicity tests in mammals, in combination with some evidence that the substance has the potentialto cause germ cells mutations (derived from mutagenicity/genotoxicity tests in germ cells in vivo, or by demonstrating the ability of the substance or its metabolite(s) to interact with the genetic material of germ cells); or (iii)tests showing mutagenic effects in the germ cells of humans, without demonstration of transmission to progeny; for example, an increase in the frequency of aneuploidy in sperm cells of exposed people.

-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 in Category 2 is based on positive evidence obtained from experiments in mammals and/or in some cases from in vitro experiments, obtained from either (i) somatic cell mutagenicitytests in vivo, in mammals; or (ii) other in vivo somatic cell genotoxicity tests which are supported by positive results from in vitro mutagenicity assays.

Regarding the present test item, negative results for bacterial mutagenicity (AMES test) were found using both plate incorporation method and pre-incubation method. Morever, in vitro mammalian cell gene mutation test using the Hprt and xprt genes and an in vivo mammalian erythrocyte micronucleus test demonstrated no concern for mutagenicity. The test item is therefore not considered mutagenic according to the CLP Regulation (EC) no. 1272/2008 and no further testing is warranted.