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.