Deoxynivalenol and Nivalenol (2nd edition) [Assuring the Maximum Level of Deoxynivalenol in Wheat] (Natural Toxins and Mycotoxins).

Food Safety Commission of Japan (FSCJ) was requested by the Ministry of Health, Labour and Welfare (MHLW) to conduct a risk assessment of deoxynivalenol (DON) to assure the maximal level for DON in foods. Previously, FSCJ had conducted a self-tasking risk assessment of DON and nivalenol (NIV) in 2010. In the current 2nd edition, only the assessment of DON has been revised. Grains contaminated with DON may be also contaminated with its derivatives, namely, 3-acetyldeoxynivalenol (3-Ac-DON), 15-acetyldeoxynivalenol (15-Ac-DON) and deoxynivalenol-3-glucoside (DON-3-glucoside). However, these substances orally ingested are rapidly biotransformed into DON. Therefore, FSCJ identified the total DON (sum of DON and its derivatives) to be assessed. The toxicity of DON was assessed based on the data of absorption-distribution-metabolism-excretion (ADME), acute toxicity, sub-acute toxicity, chronic toxicity, carcinogenicity, reproductive/developmental toxicity, genotoxicity, and immunotoxicity. DON was considered to have no significant genotoxic activity in vivo. The no-observed-adverse-effect level (NOAEL), based on the two-year chronic toxicity study in mice, was set at 0.1 mg DON/kg bw/day. By applying an uncertainty factor (UF) of 100, the TDI for DON was determined as 1 µg /kg bw/day. The average estimated exposure levels of total DON were 0.09 µg /kg bw/day and 0.22 µg/kg bw/day in the whole population and the 1-6 years group, respectively, by the Monte-Carlo method. The average exposure level in Japan was thus judged to be below the TDI, although a chance to exceed the TDI remains possible in the 1-6 years group depending on eating habits and DON contamination. For NIV, the genotoxic property was not able to be assessed due to the limited availability of the experimental data. No carcinogenic effect was observed in a two-year chronic toxicity study in mice, and the International Agency for Research on Cancer (IARC) also classifies Fusarium spp toxins including NIV to be in group 3. FSCJ thus judged that TDI can be set for NIV. Based on various toxicity studies, the TDI of NIV was determined at 0.4 µg/kg bw/day by taking into account of LOAEL 0.4 mg NIV/kg bw/day in a subacute toxicity study in rats with 90-day oral administration and UF of 1,000. The exposure level of NIV in Japan was estimated to be below the TDI. FSCJ judged it's unlikely that NIV intake leads to adverse health effects in general population.