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The substance under registration CAS 67786-25-8 is part of the Stilbene Fluorescent Whitening Agents category: within the whole category ten over fourteen registered substances (see data matrix in the Category Justification Report) were tested for bacteria reverse mutation and chromosomal aberration and none of the existing tests arisen any concern for mutagenicity or genotoxicity.

All substances of the category were modelled with the OECD Toolbox and the provisional results about mutagenicity alerts were calculated for all members and their metabolites. The same alert was reported based on the Hacceptor-path3-Hacceptor. This alert explores the possibility that a chemical interacts with DNA and/or proteins via non-covalent binding, such as DNA intercalation or groove-binding (Snyder et al. 2006). Among the descriptors potentially accounting for non-covalent interactions, the present molecular framework representing two bonded atoms connecting two H bond acceptors (calculated with software Leadscope Enteprise 2.4.15-6) resulted in an increased sensitivity/specificity for what concerns the Micronucleus training set. Experimental tests both in vivo and in vitro demonstrate that this alert is not expressed in none of the substances of the group. Based on all those considerations the available studies on the analogous substances are representative for the also that can then be considered not genotoxic (further details are given in the Category Justification Report, Section 13).

Mutagenicity in bacterial reverse mutation assays (Ames test) was investigated in two studies on the similar substance CAS 16470-24-9 (CCR Cytotest cell research GmbH, 1987 and Guenard J., 1982) with negative results.

The substance under registration was assayed for the mutagenicity by the In Vitro Mammalian Cell Gene Mutation Test. V79 hamster fibroblast were used for testing and experiments were performed without as well as with of metabolic activation using the supernatant of rat liver and a mixture of cofactors. The experiment gives no evidence of the mutagenicity of test substance, thus the test substance resulted non-mutagenic for V79 cells without as well as with metabolic activation (Täublová, 2014).

An in vivo study on the chromosomal aberration, dominant lethal assay, was performed on the substance under registration CAS 67786-25-8. The compound was administered orally in single doses to mice (NMRI) which were then mated to untreated females. 5000 mg/kg bw were given by oral gavage; pre- and post implant losses were examined. All treated animals survived. The fertility of the male animals was not influenced by the test substance. No substance related post implantation losses were recorded and no influence on rates of implants, alive and dead implants per female was found; no significant changes between control and treated groups were recorded (Bayer AG., 1977).

Furthermore, the chromosome aberration potential was investigated also for the analogous CAS 16470-24-9, both in vivo ad in vitro and the results were used as supporting studies: no indication of a mutagenic effect were recorded in the in vitro test (CCR- Cytotest Cell Research GmbH & Co. KG, 1991) and in the in vivo dominant lethal assay (Bayer AG, 1995); furthermore the substance did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse (CCR - Cytotest Cell Research GmbH & Co KG, 1991).

REFERENCES

Snyder, R. D., Ewing, D. and Hendry, L. B. 2006. DNA intercalative potential of marketed drugs testing positive in in vitro cytogenetics assays.



Justification for selection of genetic toxicity endpoint
Evaluation of the endpoint has been performed with the integrated evaluation of the following studies: in vitro Ames test (CCR Cytotest cell research GmbH 1987, Guenard J., 1982), in vitro gene mutation on mammalian cells (Täublová, 2014), in vivo chromosomal aberration (Bayer AG., 1977). The in vivo study is supported by a further dominant lethal assay, by an in vivo micronucleus assy in Bone Marrow and by an in vitro chromosome aberration assay in Chinese hamster, performed on a similar substance of the Stileben Fluorescent Whitening Agents.
Detailed justification for Read Across is indicated within any endpoint and in the Category Justification Report attached to the Section 13.

Short description of key information:
Non genotoxic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to the CLP Regulation (EC 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.

On the basis of the results of the available studies, the substance can be considered as not having mutagenic or genotoxic properties.

In conclusion, the available experimental data are adequate for classification and labelling and the substance is not classified for genetic toxicity according to the CLP Regulation (EC 1272/2008).