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

E. Dinant Kroese*, Sieto Bosgra, Harrie E. Buist, Geertje Lewin, Sander C. van der Linden, Hai-yen Man, Aldert H. Piersma, Emiel Rorije, Sjors H. W. Schulpen, Michael Schwarz, Frederik Uibel, Barbara M. A. van Vugt-Lussenburg, Andre P. M. Wolterbeek, Bart van der Burg

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    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. (C) 2014 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)11-19
    Number of pages9
    JournalReproductive Toxicology
    Volume55
    DOIs
    Publication statusPublished - 1 Aug 2015

    Funding

    This work was partially financed by the Commission of the European Communities, the collaborative project ChemScreen (GA244236).

    Keywords

    • Alternative model
    • Developmental toxicity
    • Read across
    • Grouping
    • CALUX
    • Embryonic stem cell test
    • Zebrafish embryotoxicity assay
    • ReProGlo
    • BUTYL BENZYL PHTHALATE
    • VALPROIC ACID VPA
    • DEVELOPMENTAL TOXICITY
    • AROMATASE-ACTIVITY
    • CELL-LINE
    • RATS
    • EMBRYOTOXICITY
    • CHEMICALS
    • DIFFERENTIATION
    • TERATOGENICITY

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