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

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Author: Kroese, E.D. · Bosgra, S. · Buist, H.E. · Lewin, G. · Linden, S.C. van der · Man, H.Y. · Piersma, A.H. · Rorije, E. · Schulpen, S.H.W. · Schwarz, M. · Uibel, F. · Vugt-Lussenburg, B.M.A. van · Wolterbeek, A.P.M. · Burg, B. van der
Source:Reproductive Toxicology, 55, 11-19
Identifier: 527795
doi: doi:10.1016/j.reprotox.2014.10.003
Keywords: Biology · Alternative model · CALUX · Developmental toxicity · Embryonic stem cell test · Grouping · Read across · ReProGlo · Zebrafish embryotoxicity assay · 2 ethylhexanoic acid · 2 methylhexanoic acid · Dibutyltin dichloride · monobutyltin trichloride · Monoethylhexyl phthalate · Monomethyl phthalate · Toxic substance · Tributyltin chloride · Unclassified drug · Valproic acid · Analytic method · Animal cell · Assay · CALUX battery · Chemical analysis · Chemical procedures · Chemical structure · Controlled study · Developmental toxicity · Dosimetry · Embryonic stem cell test · Embryotoxicity · Fertilization · In vitro study · Morphology · Mouse · Nonhuman · ReProGlo assay · Toxicokinetics · Zebrafish embryotoxicity test · Animalia · Danio rerio · Biomedical Innovation · Healthy Living · Life · RAPID - Risk Analysis for Products in Development · ELSS - Earth, Life and Social Sciences


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. © 2014 Elsevier Inc.