Toward relevant biomarkers in in vitro developmental toxicity and their extrapolation to the in vivo situation : Reviews

J. Louisse, R.A. Woutersen, B.J. Blaauboer, M. Verwei, I. Rietjens

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)

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. Read More: http://informahealthcare.com/doi/abs/10.1517/17425255.2012.639762
Original languageEnglish
Pages (from-to)11-27
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume8
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • stem-cell test
  • whole-embryo culture
  • gene-expression changes
  • metabolic-activation system
  • embryotoxicity tests
  • alternative methods
  • end-points
  • differentiation system
  • neural differentiation
  • maternal toxicity

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