New Publication: Potential of ToxCast Data in the Safety Assessment of Food Chemicals

The intention of this study was to determine the utility of ToxCast and Tox21 HTS data for application in toxicological read-across for a list of food-relevant chemicals. Key questions were raised as to the extent to which the HTS data could provide assistance enabling 1) the closing of existing toxicological data gaps, 2) the elucidation of underlying bioactivities associated with apical toxicological outcomes and 3) the definition of the boundaries of chemical space across which bioactivity could reliably be extrapolated. Results revealed that uncertainties with regards to the biological relevance of many of the positive hits limit in general the application of HTS for read-across purposes in particular for points 1) and 2) at this current time. As such, the focus was on the comparatively well-characterised endpoint i.e. estrogenicity and the definition of the boundaries of the chemical space across which bioactivity occurs. This was elucidated by two case studies using the chemical groups of parabens-gallates and of pyranone-type structures (notably flavonoids). Differences in the estrogenic activity of pyranone-type structures with flavones and isoflavones being more potent than various non-flavonoid pyranone compounds, illustrated the possibility to identify the out-of-domain compounds in a group based on pure structural relatives and the applicability of HTS to point 3) above.

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