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The OSIRIS Weight of Evidence approach: ITS mutagenicity and ITS carcinogenicity.

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Author: Buist, H. · Aldenberg, T. · Batke, M. · Escher, S. · Kühne, R. · Marquart, H. · Pauné, E. · Rorije, E. · Schüürmann, G. · Kroese, D.E.
Type:article
Date:2013
Source:Regulatory Toxicology and Pharmacology, 2, 67, 170-181
Identifier: 469900
doi: doi:10.1016/j.yrtph.2013.01.002
Keywords: Health Toxicology Pharmacology · Biomedical Innovation · Healthy Living · Life Triskelion · QS - Quality & Safety CRA - Chemical Risk Analysis · EELS - Earth, Environmental and Life Sciences TNO Bedrijven

Abstract

Risk assessment of chemicals usually implies data evaluation of in vivo tests in rodents to conclude on 31 their hazards. The FP7 European project OSIRIS has developed integrated testing strategies (ITS) for rel- 32 evant toxicological endpoints to avoid unnecessary animal testing and thus to reduce time and costs. This 33 paper describes the implementation of ITS mutagenicity and carcinogenicity in the public OSIRIS web- 34 tool. The data requirements of REACH formed the basis for these ITS. The main goal was to implement 35 procedures to reach a conclusion on the adequacy and validity of available data. 36 For the mutagenicity ITS a quantitative Weight of Evidence approach based on Bayesian statistics was 37 developed and implemented. The approach allows an overall quality assessment of all available data for 38 the five types of mutagenicity data requirements: in vitro bacterial mutagenicity, in vitro and in vivo chro- 39 mosome aberration, in vitro and in vivo mammalian mutagenicity. 40 For the carcinogenicity ITS a tool was developed to evaluate the quality of studies not conforming 41 (entirely) to guidelines. In a tiered approach three quality aspects are assessed: documentation (reliabil- 42 ity), study design (adequacy) and scope of examination (validity). The quality assessment is based on 43 expert and data driven quantitative Weight of Evidence.