title: Prediction of acute aquatic toxicity in Tetrahymena pyriformis--'Eco-Derek', a knowledge-based system approach.
abstract: A 'proof-of-concept' version of a software tool for making transparent predictions of acute aquatic toxicity has been developed. It is primarily limited to semi-quantitative predictions in one species, the ciliated protozoan, Tetrahymena pyriformis. A freely available system, 'Eco-Derek', was derived by adapting a well-established, knowledge-based structure-activity and reasoning platform (Derek for Windows, Lhasa Limited). The Derek reasoning code was modified to express potency rather than confidence. Structure-activity relationship (SAR) development utilised a curated version of a published dataset, supplemented with the CADASTER Challenge datasets. Forty-five structural alerts were produced. The dependence on log P was examined for each alert and entered into the system as qualitative reasoning rules specifying the predicted potency as Very Low, Low, Moderate, High or Very High. Evaluation studies showed: (a) moderate accuracy for the training set but low accuracy for an external test set; (b) non-linearity in the toxicity-log P relationship for chemicals without identified structural alerts; (c) insufficient differentiation of substituent effects in some of the reactivity-based structural alerts resulting in too few chemicals predicted with Very High toxicity; and (d) the need for additional structural alerts covering polar narcosis and less common reactive or metabolically activated chemical functionality.
authors.affiliation: Lhasa Limited, Leeds, UK. martin.payne@lhasalimited.org
authors.forename: M P
authors.initials: MP
authors.lastname: Payne
authors.forename: W G
authors.initials: WG
authors.lastname: Button
mesh_terms: D003198:Computer Simulation; D013329:Structure-Activity Relationship; D013769:Tetrahymena pyriformis / Q000187:drug effects* / Q000502:physiology; D014116:Toxicology / Q000379:methods*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical