title: Evaluation of an alternative in vitro test battery for detecting reproductive toxicants in a grouping context.
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.
authors.affiliation: TNO, Zeist, The Netherlands. Electronic address: dinant.kroese@tno.nl.
authors.forename: E Dinant
authors.initials: ED
authors.lastname: Kroese
authors.affiliation: TNO, Zeist, The Netherlands.
authors.forename: Sieto
authors.initials: S
authors.lastname: Bosgra
authors.affiliation: TNO, Zeist, The Netherlands.
authors.forename: Harrie E
authors.initials: HE
authors.lastname: Buist
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: Geertje
authors.initials: G
authors.lastname: Lewin
authors.affiliation: BioDetection Systems BV, Amsterdam, The Netherlands.
authors.forename: Sander C
authors.initials: SC
authors.lastname: van der Linden
authors.affiliation: BioDetection Systems BV, Amsterdam, The Netherlands.
authors.forename: Hai-yen
authors.initials: HY
authors.lastname: Man
authors.affiliation: Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
authors.affiliation: Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Emiel
authors.initials: E
authors.lastname: Rorije
authors.affiliation: Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Sjors H W
authors.initials: SH
authors.lastname: Schulpen
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tübingen, Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tübingen, Tübingen, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Uibel
authors.affiliation: BioDetection Systems BV, Amsterdam, The Netherlands.
authors.forename: Barbara M A
authors.initials: BM
authors.lastname: van Vugt-Lussenburg
authors.affiliation: TNO, Zeist, The Netherlands.
authors.forename: Andre P M
authors.initials: AP
authors.lastname: Wolterbeek
authors.affiliation: BioDetection Systems BV, Amsterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: van der Burg
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D011960:Receptors, Estrogen / Q000378:metabolism; D012098:Reproduction; D013723:Teratogens / Q000145:classification / Q000493:pharmacokinetics / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*; D066007:Toxicokinetics; D015027:Zebrafish / Q000196:embryology
chemical_list: D011960:Receptors, Estrogen; D013723:Teratogens
keywords: Alternative model; CALUX; Developmental toxicity; Embryonic stem cell test; Grouping; ReProGlo; Read across; Zebrafish embryotoxicity assay