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Potential of ToxCast data in the safety assessment of food chemicals

Punt, A, Firman, J, Boobis, A, Cronin, MTD, Gosling, JP, Wilks, MF, Hepburn, PA, Thiel, A and Fussell, K (2020) Potential of ToxCast data in the safety assessment of food chemicals. Toxicological Sciences. ISSN 1096-6080

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Abstract

Tox21 and ToxCast are high-throughput in vitro screening (HTS) programmes coordinated by the U.S. National Toxicology Program and the U.S. Environmental Protection Agency, respectively, with the goal of forecasting biological effects in vivo based on bioactivity profiling. The present study investigated whether mechanistic insights in the biological targets of food-relevant chemicals can be obtained from ToxCast results, when the chemicals are grouped according to structural similarity. Starting from the 556 direct additives that have been identified in the ToxCast database by Karmaus et al. (2017), the results showed that, despite the limited number of assays in which the chemical groups have been tested, sufficient results are available within so-called “DNA binding” and “nuclear receptor” target families to profile the biological activities of the defined chemical groups for these targets. The most obvious activity identified was the estrogen receptor (ER)-mediated actions of the chemical group containing parabens and structurally related gallates, as well the chemical group containing genistein and daidzein (the latter particularly towards ERβ as potential health beneficial target). These group effects, as well as the biological activities of other chemical groups, was evaluated in a series of case studies. Overall, the results of the present study suggest HTS data could add to the evidence considered for regulatory risk assessments for food chemicals and to the evaluation of desirable effects of nutrients and phytonutrients. The data will be particularly useful for providing mechanistic information and to fill data gaps with read-across.

Item Type: Article
Uncontrolled Keywords: 1115 Pharmacology and Pharmaceutical Sciences
Subjects: T Technology > TX Home economics > TX341 Nutrition. Foods and food supply
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Oxford University Press (OUP)
Date Deposited: 18 Feb 2020 11:21
Last Modified: 18 Feb 2020 11:30
DOI or Identification number: 10.1093/toxsci/kfaa008
URI: http://researchonline.ljmu.ac.uk/id/eprint/12270

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