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dc.contributor.authorLuijten, Mirjam
dc.contributor.authorWackers, Paul F K
dc.contributor.authorRorije, Emiel
dc.contributor.authorPennings, Jeroen L A
dc.contributor.authorHeusinkveld, Harm J
dc.date.accessioned2021-01-10T13:49:00Z
dc.date.available2021-01-10T13:49:00Z
dc.date.issued2020-12-30
dc.identifier.pmid33378166
dc.identifier.doi10.1021/acs.chemrestox.0c00313
dc.identifier.urihttp://hdl.handle.net/10029/624627
dc.description.abstractRecently, we reported an in vitro toxicogenomics comparison approach to categorize chemical substances according to similarities in their proposed toxicological modes of action. Use of such an approach for regulatory purposes requires, among others, insight into the extent of biological concordance between in vitro and in vivo findings. To that end, we applied the comparison approach to transcriptomics data from the Open TG-GATEs database for 137 substances with diverging modes of action and evaluated the outcomes obtained for rat primary hepatocytes and for rat liver. The results showed that a relatively small number of matches observed in vitro were also observed in vivo, whereas quite a large number of matches between substances were found to be relevant solely in vivo or in vitro. The latter could not be explained by physicochemical properties, leading to insufficient bioavailability or poor water solubility. Nevertheless, pathway analyses indicated that for relevant matches the mechanisms perturbed in vitro are consistent with those perturbed in vivo. These findings support the utility of the comparison approach as tool in mechanism-based risk assessment.en_US
dc.language.isoenen_US
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.titleRelevance of Transcriptomics for Mode of Action Assessment.en_US
dc.typeArticleen_US
dc.identifier.eissn1520-5010
dc.identifier.journalChem Res Toxicol 2021; 34:(2):452-9en_US
dc.source.journaltitleChemical research in toxicology
dc.source.countryUnited States


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