The in vivo genotoxicity studies on nivalenol and deoxynivalenol

Nivalenol (NIV) and deoxynivalenol (DON) are struct rally related mycotoxins produced by Fusarium fung i. These fungi typically infest cereal crops such as w heat, maize, barley, oats and rye, and NIV and DON are regularly found in cereal grains, food and feed. Re cent risk assessments identified possible data gaps for both DON and NIV in particular with respect to genotoxic ity and carcinogenicity. The overall objective of t he project was to assess the genotoxicity of DON and NIV, incl uding the identification of potential modes of acti on. A battery of in vivo genotoxicity tests was performed in mice: Comet as say with and without fpg in seven organs (duodenum, colon, blood, liver, spleen, kidney, bon e marrow), micronucleus assay in bone marrow and co lon, and Pig-a assay in peripheral blood. In addition, to clarify the genotoxic mode of action of both mycotoxins, w e performed in vitro Comet assay studies in TK6 cells to investigate po t ntial genotoxic oxidative stress induced by mycotoxins. The response in all the genotoxicity assays with NIV after three oral doses at 5, 10 an d 20 mg/kg, were uniformly negative. In the case of D ON, we found that DON failed to induce micronuclei formation in bone marrow and colon and failed to in duce DNA damage in all organs observed by the Comet assay with and without fpg at 4, 8 and 16 mg/kg. Th e Pig-a assay with DON after three oral gavage doses at 2, 4 and 8 mg/kg, did not show any mutagenic effect at d ay 28 and 45 after the last dose. In vitro studies indicated that both mycotoxins did not induce DNA damage in t he Comet assay with or without fpg in TK6 cells eve n after GSH depletion. It was concluded that NIV and DON could be considered as devoid of genotoxic pote ntial and pose no genotoxic or mutagenic risk. © ANSES and Institut Pasteur de Lille, 2014