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Exploring the Potential of ToxCast Data in Supporting Read-across for Evaluation of Food Chemical Safety

Firman, JW, Punt, A, Cronin, MTD, Boobis, AR, Wilks, MF, Hepburn, PA, Thief, A and Fussell, KC (2020) Exploring the Potential of ToxCast Data in Supporting Read-across for Evaluation of Food Chemical Safety. Chemical Research in Toxicology, 34 (2). pp. 300-312. ISSN 0893-228X

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The intention of this study was to determine the utility of high throughput (HTS) screening data, as exemplified by ToxCast and Tox21, for application in toxicological read-across in food-relevant chemicals. Key questions were addressed on the extent to which the HTS data could provide information enabling 1) the elucidation of underlying bioactivities associated with apical toxicological outcomes, 2) the closing of existing toxicological data gaps, and 3) the definition of the boundaries of chemical space across which bioactivity could reliably be extrapolated. Results revealed that many biological targets apparently activated within the chemical groupings lack at this time validated toxicity pathway associations. Therefore, as means of providing proof-of-principle, a comparatively well-characterised endpoint – oestrogenicity – was selected for evaluation. This was facilitated through preparation of two exploratory case studies, focusing upon groupings of paraben-gallates and pyranone-type compounds(notably flavonoids). Within both, HTS data was seen to reflect oestrogenic potencies in a manner which broadly corresponded to established structure-activity group relationships – parabens and flavonoids displaying greater oestrogen receptor affinity than benzoate esters and alternative pyranone-containing molecules respectively. As such, utility in identification of out-of-domain compounds was demonstrated, indicating potential for application in addressing point 3) as detailed above.

Item Type: Article
Uncontrolled Keywords: 0302 Inorganic Chemistry, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: American Chemical Society
Date Deposited: 12 Nov 2020 10:00
Last Modified: 11 Jan 2022 13:15
DOI or ID number: 10.1021/acs.chemrestox.0c00240
URI: https://researchonline.ljmu.ac.uk/id/eprint/13991
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