Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data

Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P.; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data

Dateien

Luechtefeld_0-365916.pdfGröße: 1.53 MBDownloads: 301

Datum

2016

Autor:innen

Luechtefeld, Thomas

Maertens, Alexandra

Russo, Daniel P.

Rovida, Costanza

Zhu, Hao

Hartung, Thomas

Angaben zur Forschungsförderung

European Union (EU): 681002

Projekt

EUToxRisk21

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Alternatives to Animal Experimentation : ALTEX. 2016, 33(2), pp. 123-134. ISSN 0946-7785. eISSN 1868-8551. Available under: doi: 10.14573/altex.1510053

Zusammenfassung

Public data from ECHA online dossiers on 9,801 substances encompassing 326,749 experimental key studies and additional information on classification and labeling were made computable. Eye irritation hazard, for which the rabbit Draize eye test still represents the reference method, was analyzed. Dossiers contained 9,782 Draize eye studies on 3,420 unique substances, indicating frequent retesting of substances. This allowed assessment of the test's reproducibility test based on all substances tested more than once. There was a 10% chance of a non-irritant evaluation given after a prior severe-irritant result as given by UN GHS classification criteria. The most reproducible outcomes were the results negative (94% reproducible) and severe eye irritant (73% reproducible). To evaluate whether other GHS categorizations predict eye irritation we built a dataset of 5,629 substances (1,931 'irritant' and 3,698 'non-irritant'). The two best decision trees with up to three other GHS classifications resulted in balanced accuracies of 68% and 73%, i.e., in the rank order of the Draize rabbit eye test itself, but both use inhalation toxicity data ("May cause respiratory irritation"), which is not typically available. Next, a dataset of 929 substances with at least one Draize study was mapped to PubChem to compute chemical similarity using 2D conformational fingerprints and Tanimoto similarity. Using a minimum similarity of 0.7 and simple classification by the closest chemical neighbor resulted in balanced accuracy from 73% over 737 substances to 100% at a threshold of 0.975 over 41 substances. This represents a strong support of read-across and (Q)SAR approaches in this area.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

LUECHTEFELD, Thomas, Alexandra MAERTENS, Daniel P. RUSSO, Costanza ROVIDA, Hao ZHU, Thomas HARTUNG, 2016. Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data. In: Alternatives to Animal Experimentation : ALTEX. 2016, 33(2), pp. 123-134. ISSN 0946-7785. eISSN 1868-8551. Available under: doi: 10.14573/altex.1510053

BibTex

@article{Luechtefeld2016Analy-35554,
  year={2016},
  doi={10.14573/altex.1510053},
  title={Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data},
  number={2},
  volume={33},
  issn={0946-7785},
  journal={Alternatives to Animal Experimentation : ALTEX},
  pages={123--134},
  author={Luechtefeld, Thomas and Maertens, Alexandra and Russo, Daniel P. and Rovida, Costanza and Zhu, Hao and Hartung, Thomas}
}

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