Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Adequate and reliable data is available for mutagenicity in vitro and in vivo. Testing was performed according or similar to OECD testing guidelines and mostly followed the principles of GLP.
Absence of mutagenicity in bacteria was reported for strains TA 100, TA 98, TA 1535, TA 1537 and TA 1538 in valid studies (MHLW 1996, ETAD, 1999) or from a reliable secondary source with little experimental detail (Seyfried 2006). In one study (Ciba 1986), a 2.9fold increase in mutant frequency was observed in strain TA 98 in the presence of metabolic activation at the highest dose of 5 mg per plate. This effect was confirmed in the repeat experiment and also found in a non-standard test performed with the same batch (Ciba 1986x). The same batch was used for testing of unscheduled DNA synthesis in primary hepatocytes, for testing of mutagenicity in the hprt test and for testing of clastogenicity in primary human lymphocytes. No genotoxic effects were observed in these studies.
The design and the metabolic activation of the varioustests is comparable, so that the singular effect is considered to be caused by a mutagenic impurity. This is supported by the fact that the effect is very weak.  
The batch that gave the weak mutagenic reponse in bacteria was not genotoxic in mammalian cells.
Overall the substance is not considered to be genotoxic in vitro.

Short description of key information:
The substance was not mutagenic in the Ames test (MHLW 1996, ETAD, 1999 and Seyfried 2006). It did not cause unscheduled DNA in primary hepatocytes (Ciba 1985 and Yoshimi 1988), was not mutagenic in mammalian cells in vitro (Ciba 1986) and not clastogenic in vitro (MHLW 1996 and Ciba 1986). No genotoxicity was observed in the micronucleus test in vivo (ETAD 1988).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for genotoxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for genotoxicity under Regulation (EC) No. 1272/2008.