uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: Results from the European Project ACuteTox
Show others and affiliations
2013 (English)In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 27, no 4, 1357-1376 p.Article in journal (Refereed) Published
Abstract [en]

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6 months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD50 > 2000 mg/kg b.w.).

Place, publisher, year, edition, pages
2013. Vol. 27, no 4, 1357-1376 p.
Keyword [en]
Acute oral toxicity, Concentration-response analysis, Classification and regression trees, In vitro, Random Forests, Testing strategy
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-202366DOI: 10.1016/j.tiv.2012.07.013ISI: 000318838000017OAI: oai:DiVA.org:uu-202366DiVA: diva2:631949
Available from: 2013-06-24 Created: 2013-06-24 Last updated: 2013-06-24Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Artursson, PerSvensson, Richard
By organisation
Department of Pharmacy
In the same journal
Toxicology in Vitro
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 167 hits
ReferencesLink to record
Permanent link

Direct link