C12-16-(even numbered)-alkyl-dimethylammonium lactate

Endpoint summary

Additional information

There is no experimental data on genetic toxicity for the registration substance N,N-dimethyl-C12-16-(even numbered)-alkyl-1-amines, lactates. The genetic toxicity of the registration substance is derived from the available data of dimethyl alkylamines (DMAs) with comparable length of alkyl chain (source substances). The source substances were tested for mutagenic potential using bacterial reverse mutation assay (Ames test), in-vitro chromosome aberration test, and in-vitro mammalian cell gene mutation tests (TK and HPRT). The results indicated that all the source substances are not mutagenic. The registration substance is assessed using the rule based expert system DEREK Nexus based on its chemical structures. The substance is predicted as negative for mutagenicity in bacteria. No toxicity potential or structure alert is identified. Based hereupon it was concluded the registration substance N,N-dimethyl-C12-16-(even numbered)-alkyl-1-amines, lactates is not mutagenic.

The analogue approach using dimethyl alkylamines (DMAs) with comparable length of alkyl chain as source chemicals is justified:

The target chemical Amines, C12-16-alkyldimethyl, lactates is an ionic compound that results from the neutralization reaction of the compounds of lactic acid and C12-16-DMA. In aqueous solution or in a biological fluid, it could be dissociate as lactic acid and C12-16-DMA. Therefore, the toxicity toxicological profile of the target chemical should be comparable to that of C12-16-DMA and lactic acid. Lactic acid is a natural, functional metabolite in mammals, and serves as mammalian fuel. From previous investigations, it is concluded that lactic acid does not present a hazard for the human health based on its low hazard profile. Based on the basic concept of “chain length category”, the use of toxicity data of other dimethyl alkylamines with comparable length of alkyl chain for read-across purpose to C12-16-DMA and the target chemical is justified. The dissociated product of the target chemical – C12-16-DMA and the source chemicals of C12-DMA, C14-DMA, C16-DMA, C18-DMA, C12-14-DMA, C12-16-DMA, C12-18-DMA and C16-18-DMA belong to the homologues series of fatty amines and form a “chain length category”, where there is an incremental increase in the number of CH2 units. Therefore, it can be reasonably assumed that C12-16-DMA and other dimethyl alkylamines (C12-DMA, C14-DMA, C16-DMA, C18-DMA, C12-14-DMA, C12-16-DMA, C12-18-DMA and C16-18-DMA) share the same toxic mode of action.

The major available physic-chemical properties of target and source chemicals are in a comparable range and support hypothesis that the source and the target chemicals behave similarly or as a function of carbon chain length.

All the chemicals are assessed using the rule based expert system DEREK Nexus based on their chemical structures. The assessment results are identical for the target chemical and source chemicals: all the chemicals are predicted as negative for mutagenicity in bacteria. No toxicity potential or structure alert is identified.

With regard to the endpoint of skin irritation/corrosion, corrosive effect was identified for the source chemicals of C12-DMA, C16-DMA, C12-14-DMA, C12-18-DMA and C16-18-DMA. The target chemical is considered as corrosive to skin (Cat 1B) based on the analogue approach. For this endpoint, the analogue approach is also justified considering the “worst case” scenario.

Based on these similarities in structural, functional and metabolic behavior of DMAs and DMA lactates, it is therefore reasonable and scientifically justified to use analogue DMAs as source molecules to inform endpoint related data gaps for the target molecule under discussion.

 

Short description of key information:
Genetic toxicity:
- Ames test (C12DMA, key): negative
- Ames test (C12DMA, non key): negative
- Ames test (C14DMA, non key): negative
- Ames test (C16DMA, non key): negative
- Ames test (C12-14DMA, non key): negative
- in-vitro chromosome aberration test (C12-18DMA, key): negative
- in-vitro mammalian cell gene mutation test (TK, C12-18DMA, key): negative
- in-vitro mammalian cell gene mutation test (HPRT, C12-18DMA, key): negative
- Ames test (C18DMA, key): negative
-(Q)SAR analysis using Derek Nexus (C12-16-DMA lactate): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available information, no genotoxic potential is derived for the registration subatance, and therefore classification for this end point is not warranted according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).