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Discriminating toxicant classes by mode of action. 4. Baseline and excess toxicity

: Nendza, M.; Müller, M.; Wenzel, A.


SAR and QSAR in Environmental Research 25 (2014), No.5, pp.393-405
ISSN: 1062-936X
ISSN: 1029-046X
Journal Article
Fraunhofer IME ()
fish toxicity; mode of action; (MOA\) classification; QSAR; reactive substructures; similarity

Functional similarity of chemicals combines toxicological knowledge (which toxicity pathways can happen in which species under which exposure conditions) with chemical expertise (which parts of the chemical structures and physico-chemical properties are involved in which interactions) to discriminate between baseline and excess toxicants. The objective is to identify as many baseline toxicants as possible because their acute fish toxicities can be predicted with sufficient accuracy from their log Kow. Established tools like structural alerts are used to indicate modes of action (MOAs) that are typical causes of excess toxicity. Verhaar classifications are supplemented with additional chemical attributes and physico-chemical property thresholds to cover a larger range of compounds within the baseline toxicity domain. Our approach is precautionary to avoid false negatives with a sensitivity of 96.3%. It classifies 57.1% of the compounds of the EPA Fathead Minnow Acute Toxicity Database (EPAFHM) as baseline toxicants and suggests that more than 50% of acute fish toxicity testing could be replaced by reliable QSAR predictions. Furthermore, functional similarity can support the MOA classification of chemicals in different species. Toxicity profiles with fish, Daphnia and algae reveal specific targets for the compounds and, particularly for chemicals with multiple MOA, identify the most sensitive species.