The effect of individual and mixtures of mycotoxins and persistent organochloride pesticides on oestrogen receptor transcriptional activation using in vitro reporter gene assays

Abstract The mycotoxins zearalenone (ZEN) and alpha-zearalenone (α-ZOL), which are common contaminants of agri-food products, are known for their oestrogenic potential. In addition to mycotoxins, food may also contain pesticides with oestrogenic properties such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane ( p,p' -DDT) and 1,1-dichloro-2,2-bis( p -chlorophenyl) ethylene ( p,p' -DDE), raising the question on the potential effects of individual and combinations of these xeno-oestrogens on the action of natural oestrogens. The present study employed a mammalian reporter gene assay to assess the effects individual and binary combinations of these environmental and food-borne contaminants on oestrogen nuclear receptor (ER) transactivation. As expected, α-ZOL and ZEN exhibited the strongest oestrogenic potency (EC 50 : 0.27 ± 0.121 nM and 1.32 ± 0.0956 nM, respectively) whereas p,p' -DDT and p,p' -DDE had weak ER agonistic activity with the maximal response of 28.70 ± 2.97% and 18.65 ± 1.77%, respectively. Concurrent treatment of the mycotoxins and/or pesticides, individually or in binary combination, with 17β-oestradiol (E 2 ) showed either additive, synergistic or antagonistic interactive effects on E 2 -mediated ER response, depending on the combination ratios, the concentration range of xeno-oestrogens, and the concentration of E 2 . This study highlights the importance of assessing the mixture effects of chemical contaminants in risk assessment, especially in the area of reproductive and developmental toxicity.