Print Email Facebook Twitter Interpreting in vitro developmental toxicity test battery results: The consideration of toxicokinetics Title Interpreting in vitro developmental toxicity test battery results: The consideration of toxicokinetics Author Bosgra, S. Westerhout, J. Publication year 2015 Abstract In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and observations of developmental toxicity in vivo. This modeling strategy is based on (1) the definition of relevant observations of toxicity in vivo, (2) simulation of the corresponding systemic concentrations in vivo by toxicokinetic modeling, and (3) correction for differences in protein binding and lipid partitioning between plasma and in vitro test media. The test results of a feasibility study with a number of known reproductive toxicants has been described previously (Piersma et al. ). In the present paper, we take a more detailed look at the toxicokinetics of these compounds, and add the analysis of some compounds from subsequent studies. We discuss how the consideration of toxicokinetics allowed comparison between test systems with differing test medium composition, has helped to interpret the in vitro findings in light of in vivo observations, and to gain confidence in the predictive value of the test battery outcomes. The same toxicokinetic modeling strategy, in reverse order, can now be used for risk assessment purposes to predict toxic doses in vivo from effective concentrations in vitro. © 2014 Elsevier Inc.. Subject LifeRAPID - Risk Analysis for Products in DevelopmentELSS - Earth, Life and Social SciencesBiomedical InnovationToxicologyHealthy LivingIn vitro test batteryIn vitro-in vivo extrapolationProtein bindingTK modelingToxicokinetics2 ethylhexanoic acidAmmonium derivativeCyclosporin ADiethylstilbestrolEndosulfanGluphosinate ammoniumHexanoic acid derivativeMethoxyacetic acidMethylhexanoic acidMethylmercuric chloridePhthalic acid 2 ethylhexyl monoesterRetinoic acidUnclassified drugValproic acidAnimal experimentClinical observationControlled studyDevelopmental toxicityIn vitro studyIn vivo studyMouseMouse defense test batteryNonhumanPredictive valueProtein bindingQuantitative analysisRatReproductive toxicityRisk assessmentSimulationToxicokinetics To reference this document use: http://resolver.tudelft.nl/uuid:b61ff211-30b2-4ec3-845b-af3fe492ad43 DOI https://doi.org/10.1016/j.reprotox.2014.11.001 TNO identifier 527797 ISSN 0890-6238 Source Reproductive Toxicology, 55, 73-80 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.