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Analysis of publically available skin sensitization data from REACH registrations 2008-2014

Analysis of publically available skin sensitization data from REACH registrations 2008-2014

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Prüfsumme: MD5:322d851ae4d218f5424b8b9b7537b627

LUECHTEFELD, Thomas, Alexandra MAERTENS, Daniel P. RUSSO, Costanza ROVIDA, Hao ZHU, Thomas HARTUNG, 2016. Analysis of publically available skin sensitization data from REACH registrations 2008-2014. In: Alternatives to Animal Experimentation : ALTEX. 33(2), pp. 135-148. ISSN 0946-7785. eISSN 1868-8551

@article{Luechtefeld2016Analy-35666, title={Analysis of publically available skin sensitization data from REACH registrations 2008-2014}, year={2016}, doi={10.14573/altex.1510055}, number={2}, volume={33}, issn={0946-7785}, journal={Alternatives to Animal Experimentation : ALTEX}, pages={135--148}, author={Luechtefeld, Thomas and Maertens, Alexandra and Russo, Daniel P. and Rovida, Costanza and Zhu, Hao and Hartung, Thomas} }

2016 Maertens, Alexandra Zhu, Hao Rovida, Costanza Hartung, Thomas Rovida, Costanza Analysis of publically available skin sensitization data from REACH registrations 2008-2014 Luechtefeld, Thomas Russo, Daniel P. 2016-10-18T08:23:40Z Luechtefeld, Thomas Maertens, Alexandra eng Zhu, Hao The public data on skin sensitization from REACH registrations already included 19,111 studies on skin sensitization in December 2014, making it the largest repository of such data so far (1,470 substances with mouse LLNA, 2,787 with GPMT, 762 with both in vivo and in vitro and 139 with only in vitro data). 21% were classified as sensitizers. The extracted skin sensitization data was analyzed to identify relationships in skin sensitization guidelines, visualize structural relationships of sensitizers, and build models to predict sensitization. A chemical with molecular weight > 500 Da is generally considered non-sensitizing owing to low bioavailability, but 49 sensitizing chemicals with a molecular weight > 500 Da were found. A chemical similarity map was produced using PubChem's 2D Tanimoto similarity metric and Gephi force layout visualization. Nine clusters of chemicals were identified by Blondel's module recognition algorithm revealing wide module-dependent variation. Approximately 31% of mapped chemicals are Michaell's acceptors but alone this does not imply skin sensitization. A simple sensitization model using molecular weight and five ToxTree structural alerts showed a balanced accuracy of 65.8% (specificity 80.4%, sensitivity 51.4%), demonstrating that structural alerts have information value. A simple variant of k-nearest neighbors outperformed the ToxTree approach even at 75% similarity threshold (82% balanced accuracy at 0.95 threshold). At higher thresholds, the balanced accuracy increased. Lower similarity thresholds decrease sensitivity faster than specificity. This analysis scopes the landscape of chemical skin sensitization, demonstrating the value of large public datasets for health hazard prediction. Russo, Daniel P. 2016-10-18T08:23:40Z Hartung, Thomas

Dateiabrufe seit 18.10.2016 (Informationen über die Zugriffsstatistik)

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