Benzoic acid, 2-hydroxy-, reaction products with formaldehyde, coupled with diazotized 5-amino-8-[[4-[(4-nitro-2-sulfophenyl)amino]phenyl]azo]-2-naphthalenesulfonic acid disodium salt

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro gene mutation study in bacteria: Positive

In vitro cytogenicity / micronucleus study: Negative

In vitro gene mutation study in mammalian cells: Negative

Additional information

The chemical structures of the organic components of the substance, assumed from the starting materials used in the manufacturing process and consequently the indicative structure, show the presence of several nitroaromatic (NO2-Ar) groups. It is well known that Salmonella typhimurium and Escherichia coli tester strains, used in the Bacterial Mutation Assay (OECD 471), are very efficient at nitroreduction, resulting in mutagenic effects mainly due to the formation of hydroxylamine moiety adducts through esterification with guanine (Roldan et al., 2008).

The mutagenic effect related to this moiety is mainly true for components without sulfonic acid groups (-SO3H) since these groups counteract the reactivity of the molecule and/or its metabolite (Benigni and Bossa, 2008).

On the other hand, mammalian cells, which also possess nitroreductases, are not efficient at nitroreduction due to the presence of oxygen under normal mammalian cell culture conditions, or in normal oxygenated tissues in vivo, thus determining an inefficient or lacking nitroreduction. Hence, a positive Ames result with nitroaromatic compounds may not be predictive of genotoxicity in mammalian systems (Kirkland et al., 2007) and the related metabolic pathway is unlikely to be relevant for humans (Kirkland et al., 2014).

Since in the Ames test the presence of NO2-Ar groups would have represented a confounding factor to investigate genotoxic effects related to potential different mechanisms of action, including those related to the presence of aromatic diazo moieties, the positive result of the Bacterial Mutation Assay (OECD 471), required for REACH Annex VII, is not considered as representative of the toxicological behaviur of the susbtance.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 1272/2008, for the purpose of the classification for germ cell mutagenicity, substances are allocated in one of two categories in consideration of the fact that they are:

- 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 or

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

 

Based on the results of mutagenicity, no classification for mutagenetic toxicity is warranted under the CLP Regulation (EC) No 1272/2008.