Evaluation of the toxic effects of food additives, alone or in mixture, in four human cell models

Food additives are present in more than 50% of food products. Several studies have suggested a link between the consumption of certain food additives and an increased risk of developing cancer. This study aimed to evaluate the genotoxicity of 32 additives and six mixtures identified by the NutriNet-Santé cohort as the most widely consumed. Genotoxicity screening was conducted using the γH2AX (for clastogenic compounds) and pH3 (for aneugenic compounds) biomarkers in four human cell models (colon, liver, kidney, and neurons) representing the target organs of food contaminants. The 32 compounds were categorized into five groups based on their toxicological profiles. Eight additives were cytotoxic, four promoted cell proliferation, two were genotoxic with a clastogenic mode of action, and the remaining 19 were neither cytotoxic nor genotoxic at the concentration tested. Among the six mixtures tested, three were neither cytotoxic nor genotoxic, one was cytotoxic, and two were genotoxic at the highest tested concentrations. The observed genotoxicity of the mixtures could not be attributed to the relative concentrations of the individual additives. These findings suggest the possibility of toxic synergies in mixtures and highlight the challenges of studying the combined effects of multiple substances.