Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Based on Read-Across with 2,2-Bis(chloromethyl)trimethylene bis[bis(2-chloroethyl)phophate


Evidence from bacterial mutagenicity studies shows that 2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] is not a bacterial cell mutagen. The test substance was also non-mutagenic in mammalian cell mutagenesis assays. In vitro, in human lymphocytes, the test substance caused a statistically significant increase in the frequency of cells with chromosome aberrations including gaps at the mid dose evaluated (312.5μg/ml) in the presence of metabolic activation only. When gap-type aberration were excluded from the analysis, the increase, while not statistically significant, was greater than the historical maximum seen in the test laboratory. The findings were, however, non-reproducible and in the absence of a dose-response effect, were not considered to be toxicologically relevant. In vivo, the test substance was not clastogenic in a mouse micronucleus test. Table 7.6. Summary of mutagenicity data









































Test



Result



Reference



In vitro plate incorporation assay, bacteria (Ames)



Non-mutagenic



CIT, 2001



In vitro plate incorporation assay, bacteria (Ames)



Non-mutagenic



Safepharm Labs Ltd. 1993



Mammalian cell gene mutation (L5178Y TK+/-cells)



Non-mutagenic



Mobil Environ. & Health Sci. Lab. 1983



Mammalian cell gene mutation (L5178Y TK+/-cells)



Non-clastogenic



Mobil Environ. & Health Sci. Lab. 1983



Induction of chromosome aberrations (Human lymphocytes)



Non-mutagenic



Safepharm Labs Ltd. 1994



In vivo Mouse Micronucleus assay



Non-clastogenic



CIT, 2002



 


Short description of key information:


The substance was not genotoxic in standard in vitro genotoxicity studies in bacterial (S. typhimurium TA1535, TA1537, TA98, TA100, TA102) and mammalian cells (mouse lymphoma L15178Y TK+/- cells, a chromosomal aberration study in mammalian cells (human lymphocytes)) with and without metabolic activation. In an in vivo mouse micronucleus test the substance was not clastogenic.


 


Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In vitro and in vivo genotoxicity tests performed with the test substance did all not indicate a possible mutagenic or genotoxic effect. Therefore the substance should not be classified for mutagenicity according to regulation (EC) 1272/2008 and EC Dir. 67/548 and adaptations.

Reference:

European Union Risk Assessment Report "2,2-Bis(chloromethyl)trimethylene bis[bis(2-chloroethyl)phophate]" (V6), CAS 38051-10-4, May 2008