Print Email Facebook Twitter Relative developmental toxicity of glycol ether alkoxy acid metabolites in the embryonic stem cell test as compared with the in vivo potency of their parent compounds Title Relative developmental toxicity of glycol ether alkoxy acid metabolites in the embryonic stem cell test as compared with the in vivo potency of their parent compounds Author de Jong, E. Louisse, J. Verwei, M. Blaauboer, B.J. van de Sandt, J.J.M. Woutersen, R.A. Rietjens, I.M.C.M. Piersma, A.H. TNO Kwaliteit van Leven Publication year 2009 Abstract The embryonic stem cell test (EST) has been proposed as an in vitro assay that might reduce animal experimentation in regulatory developmental toxicology. So far, evaluation of the EST was not performed using compounds within distinct chemical classes. Evaluation within a distinct class of chemically related compounds can define the usefulness of the assay for the chemical class tested. The aim of the present study was to evaluate the relative sensitivity of the EST for a selected series of homologous compounds and to compare the data to the relative developmental toxicity of the compounds in vivo. To this end a series of proximate developmentally toxic glycol ether alkoxy acid metabolites was tested in the EST. All glycol ether alkoxy acid metabolites tested showed a concentration-dependent inhibition of cardiomyocyte differentiation at noncytotoxic concentrations, with methoxyacetic acid as the most potent compound followed by ethoxyacetic acid, butoxyacetic acid, and phenoxyacetic acid, respectively. The potency ranking of the compounds in the EST corresponds with the available in vivo data. The relative differences between the potencies of the compounds appeared more pronounced in the in vivo studies than in the EST. A possible explanation for this discrepancy could be the difference in the kinetics of the compounds in vivo as compared with their in vitro kinetics. This study illustrates that the EST can be used to set priorities for developmental toxicity testing within classes of related compounds. © The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. Subject ChemistryToxicology and Applied PharmacologyAlternatives to animal testingDevelopmental toxicologyEmbryonic stem cellsGlycol ethersbutoxyacetic acidethoxyacetic acidglycol ether alkoxy acid metabolitemethoxyacetic acidphenoxyacetic acidtoxinunclassified druganimal cellarticlecell differentiationchemical analysischemical structureconcentration responsecontrolled studycytotoxicity testdevelopmental disorderdevelopmental toxicityembryonic stem cellembryonic stem cell testembryotoxicityheart muscle cellin vivo studymousenonhumansensitivity analysistoxicokineticsAnimal Testing AlternativesAnimalsBiotransformationCell DifferentiationCell SurvivalDose-Response Relationship, DrugEmbryonic DevelopmentEmbryonic Stem CellsGlycolsKineticsMiceModels, StatisticalMyocytes, CardiacPredictive Value of TestsReference StandardsStructure-Activity RelationshipTeratogensAnimalia To reference this document use: http://resolver.tudelft.nl/uuid:12305f7e-d8b0-425c-8146-39f77bdf1b82 DOI https://doi.org/10.1093/toxsci/kfp083 TNO identifier 241606 ISSN 1096-6080 Source Toxicological Sciences, 110 (1), 117-124 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.