Testing food-related endocrine disruptors in silico

tx-2013-00383p_0015Foodstuff should never be considered as fully safe, a priori. For example they could be a vector for naturally occurring and/or unwanted dangerous substances that can act as endocrine disruptors either as they are or after their bioactivation. The scientific community agrees that the metabolic activity of chemicals should be taken into account for proper risk assessment. Unfortunately, the in vitro evaluation of a metabolic panel and analytical/biochemical detection in food-safety assessment are very expensive and challenging because of the abundance of data to analyze.

In this context, properly validated computational protocols could be a useful tool for making metabolic and binding/activity predictions. We have applied this strategy to thioxanthone photoinitiators (TX) used in printing and identified as food contaminants after being detected in babies milk and other infant formulas, as reported by the European Food Safety Authority in 2005. Their lipophilicity suggests rapid hepatic metabolism, but the currently available data only concern 2-ITX. We have predicted phase I metabolites for the TX class of compounds and defined their binding affinity for the androgen receptor ligand-binding pocket using a local model based on available information about metabolism and androgen receptors activity. Some metabolites should undergo further in vitro or/and in vivo toxicological evaluations because they have proved to be suitable as ligands for androgen receptors.

The paper has been recently published in Chemical Research in Toxicology

Ginex, T., Dall’Asta, C., & Cozzini, P. (2014). Preliminary hazard evaluation of androgen receptor-mediated endocrine-disrupting effects of thioxanthone metabolites through structure-based molecular docking. Chemical Research in Toxicology, 27(2), 279-289.

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