Abstract

Food safety is threatened by numerous contaminants, some of which have endocrine disrupting properties. In addition, natural components in food may also interfere with the endocrine system. The exposure to chemicals via the diet occurs as a mixture rather than as individual compounds. Predicting the risks associated with chemical mixtures is one of the greatest challenges in toxicology today.We have investigated effects of imidazoles, used as pesticides in food production and flavonoids, naturally present in food of plant origin, on steroidogenic pathways in the human adrenocortical cell line H295R. Effects of single chemicals and mixtures were compared to estimated effects from the two prediction models, concentration addition and independent action.The fungicide prochloraz caused an inhibition of cortisol secretion, while the secretion of progesterone, corticosterone and aldosterone was stimulated at low doses and reduced at higher. This was explained by inhibition of CYP17 and CYP21 enzyme activities and by down-regulation of steroidogenic genes. An equimolar mixture of three imidazole compounds resulted in additive effects on cortisol secretion, which could be perfectly predicted by both prediction models. The three flavonoids daidzein, genistein and apigenin individually inhibited the secretion of cortisol, aldosterone and testosterone and caused additive effects as a mixture. Estradiol secretion, however, was significantly inhibited only by apigenin. The additive effects on hormone secretion could be described by the prediction models, except for estradiol. The mixture data and predictions suggest that additive effects should be considered in risk assessment of compounds interacting with the steroid synthesis.

Published in

Toxicology Letters
2012, Volume: 211, number: S, pages: S157

Conference

Eurotox 2012

SLU Authors

• Oskarsson, Agneta

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
UKÄ Subject classification

Environmental Health and Occupational Health


Publication identifier

DOI: https://doi.org/10.1016/j.toxlet.2012.03.571

Permanent link to this page (URI)

https://res.slu.se/id/publ/41379