Department of Preventive Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
Toxicol Sci. 2013 Jan;131(1):279-91. doi: 10.1093/toxsci/kfs286. Epub 2012 Sep 20.
Although the acute toxic effects of trichothecene mycotoxin deoxynivalenol (DON or vomitoxin), a known cause of human food poisoning, have been well characterized in several animal species, much less is known about closely related 8-ketotrichothecenes that similarly occur in cereal grains colonized by toxigenic fusaria. To address this, we compared potencies of DON, 15-acetyldeoxynivalenol (15-ADON), 3-acetyldeoxynivalenol (3-ADON), fusarenon X (FX), and nivalenol (NIV) in the mink emesis model following intraperitoneal (ip) and oral administration. All five congeners dose-dependently induced emesis by both administration methods. With increasing doses, there were marked decreases in latency to emesis with corresponding increases in emesis duration and number of emetic events. The effective doses resulting in emetic events in 50% of the animals for ip exposure to DON, 15-ADON, 3-ADON, FX, and NIV were 80, 170, 180, 70, and 60 µg/kg bw, respectively, and for oral exposure, they were 30, 40, 290, 30, and 250 µg/kg bw, respectively. The emetic potency of DON determined here was comparable to that reported in analogous studies conducted in pigs and dogs, suggesting that the mink is a suitable small animal model for investigating acute trichothecene toxicity. The use of a mouse pica model, based on the consumption of kaolin, was also evaluated as a possible surrogate for studying emesis but was found unsuitable. From a public health perspective, comparative emetic potency data derived from small animal models such as the mink should be useful for establishing toxic equivalency factors for DON and other trichothecenes.
虽然脱氧雪腐镰刀菌烯醇(DON 或呕吐毒素)的急性毒性作用,一种已知的人类食物中毒的原因,已在几种动物物种中得到很好的描述,但对于密切相关的 8-酮型镰刀菌烯醇,它们同样存在于被产毒镰刀菌定殖的谷物中,人们知之甚少。为了解决这个问题,我们比较了 DON、15-乙酰脱氧雪腐镰刀菌烯醇(15-ADON)、3-乙酰脱氧雪腐镰刀菌烯醇(3-ADON)、伏马菌素 X(FX)和雪腐镰刀菌烯醇(NIV)在腹腔内(ip)和口服给药后在水貂呕吐模型中的效力。所有五种同系物都以剂量依赖的方式通过两种给药方式引起呕吐。随着剂量的增加,呕吐潜伏期明显缩短,呕吐持续时间和呕吐次数相应增加。导致 ip 暴露于 DON、15-ADON、3-ADON、FX 和 NIV 的动物中有 50%发生呕吐的有效剂量分别为 80、170、180、70 和 60 µg/kg bw,而口服暴露时,它们分别为 30、40、290、30 和 250 µg/kg bw。这里确定的 DON 呕吐毒性与在猪和狗中进行的类似研究中报道的毒性相当,这表明水貂是一种适合研究急性镰刀菌毒素毒性的小型动物模型。还评估了基于消耗高岭土的小鼠嗜食模型作为研究呕吐的替代方法,但发现不适合。从公共卫生的角度来看,从小动物模型(如水貂)获得的比较呕吐毒性效力数据对于建立 DON 和其他镰刀菌烯醇的毒性等效因子应该是有用的。