Food Saf (Tokyo). 2020 Dec 25;8(4):115-117. doi: 10.14252/foodsafetyfscj.D-20-00031. eCollection 2020 Dec.
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 . 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 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.
日本厚生劳动省（MHLW）要求日本食品安全委员会（FSCJ）对脱氧雪腐镰刀菌烯醇（DON）进行风险评估，以确定食品中DON的最大限量。此前，FSCJ曾在2010年自行开展了对DON和雪腐镰刀菌烯醇（NIV）的风险评估。在当前的第二版中，仅对DON的评估进行了修订。受DON污染的谷物可能同时被其衍生物污染，即3-乙酰脱氧雪腐镰刀菌烯醇（3-Ac-DON）、15-乙酰脱氧雪腐镰刀菌烯醇（15-Ac-DON）和脱氧雪腐镰刀菌烯醇-3-葡萄糖苷（DON-3-葡萄糖苷）。然而，这些经口服摄入的物质会迅速生物转化为DON。因此，FSCJ确定应评估总DON（DON及其衍生物的总和）。基于吸收-分布-代谢-排泄（ADME）、急性毒性、亚急性毒性、慢性毒性、致癌性、生殖/发育毒性、遗传毒性和免疫毒性的数据，对DON的毒性进行了评估。DON被认为没有显著的遗传毒性活性。基于小鼠的两年慢性毒性研究，未观察到有害作用水平（NOAEL）设定为0.1 mg DON/kg体重/天。通过应用100的不确定性系数（UF），确定DON的每日耐受摄入量（TDI）为1 μg/kg体重/天。通过蒙特卡洛方法，全人群和1-6岁组中总DON的平均估计暴露水平分别为0.09 μg/kg体重/天和0.22 μg/kg体重/天。因此，尽管根据饮食习惯和DON污染情况，1-6岁组仍有可能超过TDI，但日本的平均暴露水平被判定低于TDI。对于NIV，由于实验数据有限，无法评估其遗传毒性特性。在小鼠的两年慢性毒性研究中未观察到致癌作用，国际癌症研究机构（IARC）也将包括NIV在内的 spp毒素归类为3类。因此，FSCJ判定可以为NIV设定TDI。基于各种毒性研究，考虑到大鼠90天口服给药亚急性毒性研究中的最低观察到有害作用水平（LOAEL）为0.4 mg NIV/kg体重/天以及1000的UF，确定NIV的TDI为0.4 μg/kg体重/天。据估计，日本NIV的暴露水平低于TDI。FSCJ判定，一般人群摄入NIV不太可能导致健康不良影响。
