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.

Keywords:

• QSAR
• ecotoxicity prediction
• knowledge base system
• structural alerts
• log P
• validation

Acknowledgements

This research was funded initially as part of a project sponsored by Defra through the Sustainable Arable LINK Programme. The authors would like to thank Rob Toy and Rich Williams (Lhasa Limited) for their invaluable work on software development and knowledge base reviewing and editing.

Notes

Presented at the 15th International Workshop on Quantitative Structure--Activity Relationships in Environmental and Health Sciences (QSAR2012), 18 -22 June 2012, Tallinn, Estonia.