In silico and in vitro prediction of the toxicological effects of individual and combined mycotoxins

3-Acetyldeoxynivalenol (3-AcDON) and 15-acetyldeoxynivalenol (15-AcDON) are converted to deoxynivalenol (DON) in vivo and their simultaneous presence may increase DON intake. Mixtures of DON and its derivatives are a public health concern. In this study DON, 3-AcDON and 15-AcDON were evaluated in vitro and in silico. The in vitro cytotoxicity of DON and its derivatives individually and combined was determined by the Neutral Red (NR) assay in human hepatocarcinoma (HepG2) cells. The concentrations tested were from 1.25 to 15 mu M (DON) and from 0.937 to 7.5 mu M (DON derivatives). The IC50 values were from > 15 to 2.55 mu M (DON), from 1.77 to 1.02 mu M (3-AcDON), and from 4.05 to 1.68 mu M (15-AcDON). 3-AcDON was the most cytotoxic molecule in HepG2 cells. The concentrations tested in combinations ranged from 0.5625 to 4.5 mu M (DON), and from 0.094 to 0.75 mu M (DON derivatives), with ratios of 1:6 (DON + 3-AcDON and DON + 15-AcDON), 1:1 (3-AcDON + 15-AcDON) and 1:6:6 (DON + 3-AcDON + 15-AcDON). The DON + 15-AcDON mixture exhibited additive effects, while the rest showed synergistic effects. In silico methods assess individual mycotoxins. Absorption, Distribution, Metabolism, Excretion and Toxicity of mycotoxins were predicted using in silico SwissADME tools. Absorption, Distribution, Metabolism and Excretion profile prediction shows high gastrointestinal absorption and CYP3A4 mediated metabolism.