Evaluation of an alternative in vitro test battery for detecting reproductive toxicants in a grouping context

Previously we showed a battery consisting of CALUX transcriptional activation assays, the ReProGlo assay, and the embryonic stem cell test, and zebrafish embryotoxicity assay as ‘apical’ tests to correctly predict developmental toxicity for 11 out of 12 compounds, and to explain the one false negati...

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Bibliographic Details
Published in:Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2015-08, Vol.55, p.11-19
Main Authors: Kroese, E. Dinant, Bosgra, Sieto, Buist, Harrie E., Lewin, Geertje, van der Linden, Sander C., Man, Hai-yen, Piersma, Aldert H., Rorije, Emiel, Schulpen, Sjors H.W., Schwarz, Michael, Uibel, Frederik, van Vugt-Lussenburg, Barbara M.A., Wolterbeek, Andre P.M., van der Burg, Bart
Format: Article
Language:English
Subjects:
Alternative model
Animal Testing Alternatives
Animals
CALUX
Cell Line
Cells, Cultured
Danio rerio
Developmental toxicity
Embryo, Nonmammalian - drug effects
Embryonic stem cell test
Embryonic Stem Cells - drug effects
Genes, Reporter
Grouping
Humans
Mice
Read across
Receptors, Estrogen - metabolism
Reproduction
ReProGlo
Teratogens - classification
Teratogens - pharmacokinetics
Teratogens - toxicity
Toxicity Tests - methods
Toxicokinetics
Zebrafish - embryology
Zebrafish embryotoxicity assay
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Summary:Previously we showed a battery consisting of CALUX transcriptional activation assays, the ReProGlo assay, and the embryonic stem cell test, and zebrafish embryotoxicity assay as ‘apical’ tests to correctly predict developmental toxicity for 11 out of 12 compounds, and to explain the one false negative [7]. Here we report on applying this battery within the context of grouping and read across, put forward as a potential tool to fill data gaps and avoid animal testing, to distinguish in vivo non- or weak developmental toxicants from potent developmental toxicants within groups of structural analogs. The battery correctly distinguished 2-methylhexanoic acid, monomethyl phthalate, and monobutyltin trichloride as non- or weak developmental toxicants from structurally related developmental toxicants valproic acid, mono-ethylhexyl phthalate, and tributyltin chloride, respectively, and, therefore, holds promise as a biological verification model in grouping and read across approaches. The relevance of toxicokinetic information is indicated.
ISSN:0890-6238
1873-1708
DOI:10.1016/j.reprotox.2014.10.003