Title
Toward in vitro biomarkers for developmental toxicity and their extrapolation to the in vivo situation
Author
Louisse, J.
Verwei, M.
Woutersen, R.A.
Blaauboer, B.J.
Rietjens, I.M.C.M.
Publication year
2012
Abstract
Introduction: Reliable in vitro and in silico assays as alternatives for in vivo developmental toxicity studies are urgently needed, for the replacement, reduction and refinement (3Rs) of animal use in toxicological research. Therefore, relevant biomarkers for in vivo developmental toxicity in in vitro assays are needed. Areas covered: The present review gives an overview of alternative assays, as described in literature, for in vivo developmental toxicity, including the effects (readouts) assessed in these assays. The authors discuss how these data may be used to obtain relevant biomarkers for in vivo developmental toxicity, and how in vitro effect data can be translated to the in vivo situation using physiologically based kinetic (PBK) modeling. Expert opinion: Relevance of readouts in in vitro developmental toxicity assays as predictive biomarkers for in vivo developmental toxicity should be evaluated by comparing the obtained in vitro effect concentrations with in vivo internal concentrations at dose levels causing developmental toxicity. Extrapolation of the in vitro effect concentrations to in vivo dose levels using PBK modeling (i.e., reverse dosimetry) is promising in its use to derive points of departure for risk assessment, enabling the use of in vitro toxicity data in the safety assessment of compounds.
Subject
Life
PHS - Pharmacokinetics & Human Studies RAPID - Risk Analysis for Products in Development
EELS - Earth, Environmental and Life Sciences
Biomedical Innovation
Biology
Healthy Living Healthy Living
3Rs
Biomarkers
Developmental toxicity
Embryotoxicity
in vitro
Kinetic modeling
To reference this document use:
http://resolver.tudelft.nl/uuid:5c241f08-8845-467d-887d-611200090959
DOI
https://doi.org/10.1517/17425255.2012.63976
TNO identifier
445686
ISSN
1742-5255
Source
Expert Opinion on Drug Metabolism and Toxicology, 8 (1), 11-27
Document type
article