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dc.contributor.authorMEEK M. E.en_GB
dc.contributor.authorBOOBIS Alanen_GB
dc.contributor.authorCOTE Ilaen_GB
dc.contributor.authorDELLARCO Vickien_GB
dc.contributor.authorFOTAKIS Georgeen_GB
dc.contributor.authorMUNN SHARONen_GB
dc.contributor.authorSEED Jenniferen_GB
dc.contributor.authorVICKERS Carolynen_GB
dc.identifier.citationJOURNAL OF APPLIED TOXICOLOGY vol. 34 no. 1 p. 1-18en_GB
dc.description.abstractThe World Health Organization/International Programme on Chemical Safety mode of action/human relevance framework has been updated to reflect experience acquired in its application and extend its utility to emerging areas in toxicity testing and non-testing methods. The underlying principles have not changed, but the framework’s scope has been extended to enable integration of information at different levels of biological organization and reflect evolving experience in a much broader range of potential applications. Mode of action/species concordance analysis can also inform hypothesis-based data generation and research priorities in support of risk assessment. The modified framework is incorporated within a roadmap, with feedback loops encouraging continuous refinement of fit-for-purpose testing strategies and risk assessment. Important in this construct is consideration of dose–response relationships and species concordance analysis in weight of evidence. The modified Bradford Hill considerations have been updated and additionally articulated to reflect increasing experience in application for cases where the toxicological outcome of chemical exposure is known. The modified framework can be used as originally intended, where the toxicological effects of chemical exposure are known, or in hypothesizing effects resulting from chemical exposure, using information on putative key events in established modes of action from appropriate in vitro or in silico systems and other lines of evidence. This modified mode of action framework and accompanying roadmap and case examples are expected to contribute to improving transparency in explicitly addressing weight of evidence considerations in mode of action/species concordance analysis based on both conventional data sources and evolving methods.en_GB
dc.description.sponsorshipJRC.I.5-Systems Toxicologyen_GB
dc.titleNew developments in the evolution and application of the WHO/IPCS framework on mode of action/species concordance analysisen_GB
dc.typeArticles in periodicals and booksen_GB
JRC Directorate:Institute for Health and Consumer Protection Historical Collection

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