Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Read-across justification

Genetic toxicity in vitro data on v516690 (IUPAC name 4-[2-[(E)-2-[(3E)-2-chloro-3-[(2E)-2-[1,1-dimethyl-3-(4-sulfobutyl)benzo[e]indol-2-ylidene]ethylidene]inden-1-yl]vinyl]-1,1-dimethyl-benzo[e]indol-3-ium-3-yl]butane-1-sulfonate) is a data requirement for REACH dossiers 1-10 tonnes/year. Since information on this endpoint is lacking for this substance, read-across to the structurally similar substance infrazam (EC number: 700-626-0; CAS number: 1073607-50-7) is suggested. RAAF scenario 2 is applicable since the hypothesis is based on a different compound having the same type of effect. 

The target substance has an additional aromatic group in comparison to infrazam.

Based on the OECD QSAR toolbox profiling application, both substances have a similar profile: both are not considered estrogen receptor binders, are not expected to bind to proteins (OASIS v1.1 and OECD) and fall within the same Cramer class (Class III) (possible significant toxicity).

Regarding in vitro mutagenicity (Ames alerts by ISS) no alert was found for both substances.

However, both substances have a H-acceptor-path3-H-acceptor alert (in vivo mutagenicity alerts by ISS). This alert explores the possibility that a chemical could potentially interact with DNA and/or proteins via non-covalent binding (Snyder et al. 2006[1]).

The only difference between the source and target substance in OECD QSAR toolbox is a structural alert for genotoxic carcinogenicity, only for v516690 based on alkenylbenzene presence. However the alkenyl-group should be available to react which is not the case, since the alkenyl group is part of a ring. This difference can therefore be refuted and is not considered relevant.

 

Biotransformation of both substances can be expected. OECD QSAR toolbox did not find any observed metabolites, but renders only simulated metabolites. The mechanism of biotransformation is expected to be very similar and not trigger any additional toxicity.

 

A genetic in vitro study is available for infrazam in which the read-across substance is not considered as genetic toxic. Since the read-across substance is structurally very similar and no additional alerts have been found in OECD QSAR toolbox, it can be concluded that v516690 is not genetic toxic as well.  

 

[1]Snyder, R. D., Ewing, D. and Hendry, L. B. 2006. DNA intercalative potential of marketed drugs testing positive inin vitrocytogenetics assays.Mutat. Res.609, 47-59.


Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification