L-Valine, N-[(1,1-dimethylethoxy)carbonyl]-, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester

Endpoint summary

Additional information

Different in silico approaches were applied, including the read-across and QSAR models. In addition, different QSAR tools were used, when possible, in order to apply a consensus approach to enhance the reliability of the predictions. In fact, when multiple models and multiple approaches are combined in a consensus analysis, more accurate predictions can be achieved. In general, the consensus approach was performed according to the precautionary principle and weighting QSAR results more than the read-across results, since they are considered more reliable and scientifically robust.

Short description of key information:
The conclusions were derived based on the read across study and the QSAR predictions.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Mutagenicity (Ames test).

Despite the QSAR Toolbox identified in the target chemical a potentially genotoxic functional group, i.e. carbamate group, which is not present in the source chemical, the read across approach could be applied because it was noted that the target carbamate is more precisely a tert-butyl carbamate, known to be very stable towards most nucleophiles and bases, very little reactive and thus not likely to play an important role on the genotoxicity of the target chemical. Thus, the experimental test result of the source chemical was read-across to L-Valine, N-[(1,1-dimethylethoxy)carbonyl]-, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester, concluding that L-Valine, N-[(1,1 - dimethylethoxy)carbonyl]-, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester is NOT MUTAGEN.

This conclusion was further confirmed by the QSAR predictions: the L-Valine, N-[(1,1-dimethylethoxy)carbonyl]-, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester, was in fact, predicted negative on Ames test and negative for chromosome aberrations on rat. The prediction for micronucleous test on rodent resulted positive, but the prediction was considered borderline. Finally the only identified potentially alert for genotoxic carcinogenicity was the alkyl carbamate, already commented for not being likely to cause genotoxic activity because of the presence of the protective tert-butyl group. Thus, it is finally concluded that L-Valine, N-[(1,1-dimethylethoxy)carbonyl]-, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester is NOT GENOTOXIC.