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

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


Reproductive toxicology 55 (2015), pp.11-19
ISSN: 0890-6238
ISSN: 1873-1708
Journal Article
Fraunhofer ITEM ()
alternative model; CALUX; developmental toxicity; embryonic stem cell test; grouping; ReProGlo; read across; zebrafish embryotoxicity assay

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 (Piersma et al., 2013 [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.