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Toxicol Sci. 2020 Apr 1;174(2):326-340. doi: 10.1093/toxsci/kfaa008.

Potential of ToxCast Data in the Safety Assessment of Food Chemicals.

Author information

1
Wageningen Food Safety Research, 6700 AE Wageningen, The Netherlands.
2
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
3
National Heart & Lung Institute, Imperial College London, London W12 0NN, UK.
4
School of Mathematics, University of Leeds, Leeds LS2 9JT, UK.
5
Swiss Centre for Applied Human Toxicology, University of Basel, 4055 Basel, Switzerland.
6
Unilever, Safety & Environmental Assurance Centre, Colworth Science Park, Sharnbrook MK44 1LQ, UK.
7
DSM Nutritional Products, 4303 Kaiseraugst, Switzerland.
8
Nestlé Research, CH-1000 Lausanne, Switzerland.

Abstract

Tox21 and ToxCast are high-throughput in vitro screening programs 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. [Karmaus, A. L., Trautman, T. D., Krishan, M., Filer, D. L., and Fix, L. A. (2017). Curation of food-relevant chemicals in ToxCast. Food Chem. Toxicol. 103, 174-182.], 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-mediated actions of the chemical group containing parabens and structurally related gallates, as well the chemical group containing genistein and daidzein (the latter 2 being particularly active toward estrogen receptor β as a potential health benefit). These group effects, as well as the biological activities of other chemical groups, were evaluated in a series of case studies. Overall, the results of the present study suggest that high-throughput screening data could add to the evidence considered for regulatory risk assessment of 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.

KEYWORDS:

ToxCast; food chemicals; high-throughput in vitro screening; read-across; risk-benefit

PMID:
32040188
DOI:
10.1093/toxsci/kfaa008

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