Title
Evaluation of an alternative in vitro test battery for detecting reproductive toxicants
Author
Piersma, A.H.
Bosgra, S.
van Duursen, M.B.M.
Hermsen, S.A.B.
Jonker, L.R.A.
Kroese, E.D.
van der Linden, S.C.
Man, H.
Roelofs, M.J.E.
Schulpen, S.H.W.
Schwarz, M.
Uibel, F.
van Vugt-Lussenburg, B.M.A.
Westerhout, J.
Wolterbeek, A.P.M.
van der Burg, B.
Publication year
2013
Abstract
The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays. © 2013.
Subject
Life
QS - Quality & Safety RAPID - Risk Analysis for Products in Development
EELS - Earth, Environmental and Life Sciences
Biomedical Innovation
Biology
Healthy Living
Alternative assay
Aromatase
CALUX
Embryonic stem cell test
ReProGlo
Test battery
Toxicokinetics
Zebrafish embryotoxicity assay
To reference this document use:
http://resolver.tudelft.nl/uuid:57b03d9c-0908-400a-a5e9-3fe6868ea773
DOI
https://doi.org/10.1016/j.reprotox.2013.03.002
TNO identifier
471992
ISSN
0890-6238
Source
Reproductive Toxicology, 38, 53-64
Document type
article