The problem of how to deal with species sensitivity differences to toxic substances has been addressed successfully with the species sensitivity distribution (SSD), yet this has not increased understanding about the underlying mechanisms of sensitivity. Other researchers have identified the mode of action of chemicals and also biological traits of species as determinants for sensitivity, yet no systematic approach combines these factors. To achieve this, first existing data on organophosphate, carbamate, and pyrethroid toxicity and mode of action and also species trait information were mined. Second, we linked taxon sensitivity to their traits at the family level to generate empirical and mechanistic hypotheses about sensitivity–trait relationships. In this way, a mode-specific sensitivity (MSS) ranking method was developed, and tested at the taxonomic level of family and genus. The application of several quality criteria indicated overall confidence in rankings, but confidence in exact taxon rank was less certain, due to data insufficiency for certain groups. The MSS rankings were found to be applicable for trait-based approaches and were successfully linked to existing trait data to identify traits with predictive potential. Although this empirical analysis cannot test causality relationships between traits and sensitivity, testable hypotheses were generated, for further experimental investigation. Single traits as well as combinations of traits can be used to predict laboratory sensitivity to the substances tested, although associations were not as strong as in previous studies. We conclude that existing trait data are not suitable for every trait-based research question and that important traits remain to be identified and quantified in relation to the processes of toxicity, i.e., the toxicokinetics and toxicodynamics. Environ. Toxicol. Chem. 2010;29:476–487. © 2009 SETAC
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