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dc.contributor.authorPRIETO PERAITA MARIA DEL PILARen_GB
dc.contributor.authorGRAEPEL RABEAen_GB
dc.contributor.authorGERLOFF KIRSTEN BRITTAen_GB
dc.contributor.authorLAMON LARAen_GB
dc.contributor.authorSACHANA MAGDALINIen_GB
dc.contributor.authorPISTOLLATO FRANCESCAen_GB
dc.contributor.authorGRIBALDO LAURAen_GB
dc.contributor.authorPRICE ANNAen_GB
dc.contributor.authorWORTH ANDREWen_GB
dc.date.accessioned2018-09-26T00:18:43Z-
dc.date.available2018-09-24en_GB
dc.date.available2018-09-26T00:18:43Z-
dc.date.created2018-07-25en_GB
dc.date.issued2018en_GB
dc.date.submitted2018-04-20en_GB
dc.identifier.citationALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION p. 1-24en_GB
dc.identifier.issn1868-596Xen_GB
dc.identifier.urihttps://doi.org/10.14573/altex.1805181en_GB
dc.identifier.urihttp://publications.jrc.ec.europa.eu/repository/handle/JRC111713-
dc.description.abstractThe replacement of animals in acute systemic toxicity testing remains a considerable challenge. Only animal data are currently accepted by regulators, including data generated by reduction and refinement methods. The development of Integrated Approaches to Testing and Assessment (IATA) is hampered by an insufficient understanding of the numerous toxicity pathways that lead to acute systemic toxicity. Therefore, central to our work has been the collection and evaluation of the mechanistic information on eight organs identified as relevant for acute systemic toxicity (nervous system, cardiovascular system, liver, kidney, lung, blood, gastrointestinal system and immune system). While the nervous and cardiovascular systems are the most frequent targets, no clear relationship emerged between specific mechanisms of target organ toxicity and the level (category) of toxicity. From a list of 114 chemicals with acute oral in vivo and in vitro data, 97 were identified with target organ specific effects, of which 94% (91/97) were predicted as acutely toxic by the 3T3 neutral red uptake cytotoxicity assay and 6% (6/97) as non-toxic. Although specific target organ mechanisms of toxicity could in some cases explain the false negative prediction obtained with the cytotoxicity assay, in general it is difficult to explain in vitro misclassifications only on the basis of mechanistic information. This analysis will help to prioritise the development of adverse outcome pathways for acute oral toxicity, which will support the assessment of chemicals using mechanistically informed IATA.en_GB
dc.description.sponsorshipJRC.F.3-Chemicals Safety and Alternative Methodsen_GB
dc.format.mediumPrinteden_GB
dc.languageENGen_GB
dc.publisherSPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBHen_GB
dc.relation.ispartofseriesJRC111713en_GB
dc.titleInvestigating cell type specific mechanisms contributing to acute oral toxicityen_GB
dc.typeArticles in periodicals and booksen_GB
dc.identifier.doi10.14573/altex.1805181en_GB
JRC Directorate:Health, Consumers and Reference Materials

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