Exploring the Potential of ToxCast Data in Supporting Read-Across for Evaluation of Food Chemical Safety
Autor: | Paul A Hepburn, Ans Punt, Alan R. Boobis, James W. Firman, Martin F. Wilks, Karma C. Fussell, Anette Thiel, Mark T. D. Cronin |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
RM
Novel Foods & Agrochains BU Toxicologie Team Toxicology Computational biology 010501 environmental sciences Biology Toxicology Novel Foods & Agroketens 01 natural sciences Risk Assessment 03 medical and health sciences QH301 Structure-Activity Relationship Chemical safety Toxicity Tests Life Science Humans QD BU Toxicology Novel Foods & Agrochains 030304 developmental biology 0105 earth and related environmental sciences Pyrans Flavonoids 0303 health sciences Molecular Structure BU Toxicology General Medicine Chemical space High-Throughput Screening Assays BU Toxicologie Novel Foods & Agroketens |
Zdroj: | Chemical Research in Toxicology 34 (2021) 2 Chemical Research in Toxicology, 34(2), 300-312 |
ISSN: | 0893-228X |
DOI: | 10.1021/acs.chemrestox.0c00240 |
Popis: | The intention of this study was to determine the utility of high-throughput screening (HTS) 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-characterized end point - estrogenicity - was selected for evaluation. This was facilitated through the preparation of two exploratory case studies, focusing upon groupings of paraben-gallates and pyranone-type compounds (notably flavonoids). Within both, the HTS data were seen to reflect estrogenic potencies in a manner which broadly corresponded to established structure-activity group relationships, with parabens and flavonoids displaying greater estrogen receptor affinity than benzoate esters and alternative pyranone-containing molecules, respectively. As such, utility in the identification of out-of-domain compounds was demonstrated, indicating potential for application in addressing point (3) as detailed above. |
Databáze: | OpenAIRE |
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