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Towards new computational tools for predicting toxicity
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.ORCID iD: 0000-0003-4158-4148
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The toxicological screening of the numerous chemicals that we are exposed to requires significant cost and the use of animals. Accordingly, more efficient methods for the evaluation of toxicity are required to reduce cost and the number of animals used. Computational strategies have the potential to reduce both the cost and the use of animal testing in toxicity screening. The ultimate goal of this thesis is to develop computational models for the prediction of toxicological endpoints that can serve as an alternative to animal testing. In Paper I, an attempt was made to construct a global quantitative structure-activity relationship (QSAR)model for the acute toxicity endpoint (LD50 values) using the Munro database that represents a broad chemical landscape. Such a model could be used for acute toxicity screening of chemicals of diverse structures. Paper II focuses on the use of acute toxicity data to support the prediction of chronic toxicity. The results of this study suggest that for related chemicals having acute toxicities within a similar range, their lowest observed effect levels (LOELs) can be used in read-across strategies to fill gaps in chronic toxicity data. In Paper III a k-nearest neighbor (k-NN) classification model was developed to predict human ether-a-go-go related gene (hERG)-derived toxicity. The results suggest that the model has potential for use in identifying compounds with hERG-liabilities, e.g. in drug development.

Place, publisher, year, edition, pages
Växjö: Linnaeus University Press, 2016. , 68 p.
Linnaeus University Dissertations, 243/2016
Keyword [en]
Acute toxicity, chronic toxicity, hERG, k-NN, LD50, LOEL, Munro database, QSAR, read-across, toxicity
National Category
Bioinformatics and Systems Biology
Research subject
Chemistry, Medical Chemistry
URN: urn:nbn:se:lnu:diva-51336ISBN: 978-91-88357-04-5OAI: diva2:914669
Public defence
2016-04-15, N2007, Norra vägen 49, Kalmar, 09:30 (English)
Available from: 2016-03-29 Created: 2016-03-24 Last updated: 2016-03-29Bibliographically approved

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Chavan, Swapnil
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