External validation of acute-to-chronic models for estimation of reproductive toxicity to Daphnia magna

We evaluated the predictivity and applicability of previously proposed models for the reproductive toxicity of chemicals to Daphnia magna [SAR QSAR Environ. Res. 27:10, 833–850] by using external data from the United States Environmental Protection Agency database ECOTOX. These models were based on quantitative structure–activity–activity relationships (QSAARs) and a quantitative activity–activity relationship (QAAR): the models can be categorized as acute-to-chronic models with (QSAAR) and without (QAAR) structural and physicochemical (e.g. distribution coefficients, log D) descriptors. We found that the QSAAR models were suitable for chemicals with an ‘–NH2 attached to aromatic carbon’ sub-structure, whereas the QAAR model was better for multicomponent compounds, coordination complexes, tin compounds and straight-chain primary amines. For chemicals with a known specific mode of action (e.g. pesticides and antibacterial agents and their derivatives), toxicity estimation within the acute-to-chronic framework requires special attention. We evaluated the applicability of the models on the basis of the descriptors in the models. We recommend that chemicals be pre-screened before their toxicities are estimated with these models: pre-screening enabled the estimation of the toxicities of some chemicals within the applicability domains of the models.