Mixtures health effects: mycotoxins in food

Abstract

In recent years, the risk assessment paradigm has shifted from the single-exposure and single-chemical adverse effect scenario to the one of multiple exposures and combined adverse effects. The present work describes the in vitro combined toxicity of mycotoxins at the renal level, as a case study. Mycotoxins are often present in food and feed, as secondary metabolites of contaminating fungi and human co-exposure mainly occurs though diet. Even though predictions about the toxic effects of mycotoxins mixtures can be based on their individual toxicities, experimental data is still limited to allow a reliable hazard assessment. This study aimed at characterizing the combined cytotoxic and genotoxic effects of ochratoxin A (OTA) and fumonisin B1 (FB1), in a kidney human cell line. The toxicity of several combinations of OTA and FB1 was compared with their individual toxicities (MTT assay) and interactions were ascertained using the reference models of concentration addition and independent action. A synergistic pattern for combinations of FB1 with the lower doses of OTA was detected, shifting to antagonism at higher dose levels, irrespectively of the reference model applied. Neither OTA nor FB1, individually or in combination, were genotoxic. In conclusion, this study revealed that, OTA and FB1 exert a synergistic toxic effect at the lowest dose levels, which are the most realistic ones in terms of human co-exposure. This finding emphasizes the relevance of assessing the combined toxicity of mycotoxins to allow the development of qualitative/semi-quantitative or probabilistic models for the hazard assessment of combined human exposure to these food contaminants.