title: Ecotoxicity prediction using mechanism- and non-mechanism-based QSARs: a preliminary study.
abstract: In ecotoxicology, mechanism-based quantitative structure-activity relationships (QSARs) are usually developed with higher quality than QSARs without regard to toxicity mechanism. Correctly determining the mechanism of a compound, which is not always easy, is required to use mechanism-based QSARs for toxicity prediction. The mechanism determination step may introduce extra errors in addition to the intrinsic prediction errors of mechanism-based QSARs, thus compromising these QSARs' performance compared with QSARs regardless of mechanism. In this study, the mechanism identification-toxicity prediction (MI-TP) approach was compared with the direct toxicity prediction (DTP) approach using a data set containing phenol toxicity to Tetrahymena pyriformis. A statistical mechanism classification model for mechanism prediction, four mechanism-based QSARs and a single QSAR without discriminating between mechanisms were developed for toxicity prediction. Toxicity of phenols in an external data set was predicted following the MI-TP and DTP approaches. Results indicated that the mechanisms of several phenols in the external test set were incorrectly predicted which led to significant over- or under-estimation of their toxicity. Overall, the MI-TP approach did not yield more accurate toxicity prediction than the DTP approach.
mesh_terms: D000818:Animals; D015233:Models, Statistical; D019800:Phenol / Q000145:classification / Q000633:toxicity*; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D013769:Tetrahymena pyriformis / Q000502:physiology*; D014116:Toxicology / Q000379:methods*
chemical_list: D019800:Phenol