Title
The OSIRIS Weight of Evidence approach: ITS for the endpoints repeated-dose toxicity (RepDose ITS)
Author
Tluczkiewicz, I.
Batke, M.
Kroese, D.
Buist, H.
Aldenberg, T.
Pauné, E.
Grimm, H.
Kühne, R.
Schüürmann, G.
Mangelsdorf, I.
Escher, S.E.
TNO Kwaliteit van Leven
KvL
Publication year
2013
Abstract
In the FP6 European project OSIRIS, Integrated Testing Strategies (ITSs) for relevant toxicological endpoints were developed to avoid new animal testing and thus to reduce time and costs. The present paper describes the development of an ITS for repeated-dose toxicity called RepDose ITS which evaluates the conditions under which in vivo non-guideline studies are reliable. In a tiered approach three aspects of these "non-guideline" studies are assessed: the documentation of the study (reliability), the quality of the study design (adequacy) and the scope of examination (validity).The reliability is addressed by the method "Knock-out criteria", which consists of four essential criteria for repeated-dose toxicity studies. A second tool, termed QUANTOS (Quality Assessment of Non-guideline Toxicity Studies), evaluates and weights the adequacy of the study by using intra-criterion and inter-criteria weighting. Finally, the Coverage approach calculates a probability that the detected Lowest-Observed-Effect-Level (LOEL) is similar to the LOEL of a guideline study dependent on the examined targets and organs of the non-guideline study. If the validity and adequacy of the non-guideline study are insufficient for risk assessment, the ITS proposes to apply category approach or the Threshold of Toxicological Concern (TTC) concept, and only as a last resort new animal-testing. © 2013 Elsevier Inc.
Subject
Life
QS - Quality & Safety
EELS - Earth, Environmental and Life Sciences
Biomedical Innovation
Biology
Healthy Living
3R principle
Alternative
Integrated Testing Strategy
ITS
Non-testing method
OSIRIS
Repeated-dose
Risk Assessment
TTC
Weighting
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DOI
https://doi.org/10.1016/j.yrtph.2013.02.004
TNO identifier
482960
ISSN
0273-2300
Source
Regulatory Toxicology and Pharmacology, 67 (2), 157-169
Document type
article