麻痹性贝类中毒是由麻痹性贝类毒素污染的贝类引起的世界性问题。为了保护人类健康,许多国家已经采用了贝类中这些毒素的监管限制。在最近的一项研究中,每天给小鼠服用毒素和河豚毒素混合物,持续28天,在低浓度下显示毒性,这似乎与其他工作不一致。为了进一步研究这种报道的毒性,我们每天给小鼠组服用沙鼠毒素和河豚毒素混合物,共21天。与之前的研究相比,对小鼠体重没有影响,食物消费,心率,血压,握力,观察血液化学或血液学。此外,在本试验中,没有组织学发现与给药相关.本研究的剂量率分别为2.6、3.8和4.9倍,分别,比之前研究的最高剂量。由于在先前的研究中观察到五分之三的小鼠快速死亡,死亡可能是由于使用的方法,而不是贝类毒素。要将动物数据转换为人类风险评估中使用的数据,100倍的安全系数是必需的。应用此安全系数后,当前研究中使用的剂量率是3.5、5.0和6.5倍,分别,而不是欧盟设定的每种毒素类型的急性参考剂量。此外,以前有人建议将河豚毒素包括在麻痹性贝类中毒毒素套件中。如果这样做了,本研究中使用的最高剂量率是急性参考剂量的13倍.这项研究表明,先前的28天试验存在缺陷,并且目前的麻痹性贝类毒素监管限制符合目的。一项额外的研究,给小鼠喂食比当前实验更高浓度的测试化合物的饮食,将被要求评论是否应修改当前的麻痹性贝类毒素监管限制。
Paralytic shellfish poisoning is a worldwide problem induced by shellfish contaminated with paralytic shellfish toxins. To protect human health, a regulatory limit for these toxins in shellfish flesh has been adopted by many countries. In a recent
study, mice were dosed with
saxitoxin and tetrodotoxin mixtures daily for 28 days showing toxicity at low concentrations, which appeared to be at odds with other work. To further investigate this reported toxicity, we dosed groups of mice with
saxitoxin and tetrodotoxin mixtures daily for 21 days. In contrast to the previous study, no effects on mouse bodyweight, food consumption, heart rate, blood pressure, grip strength, blood chemistry or hematology were observed. Furthermore, no histological findings were associated with dosing in this
trial. The dose rates in this study were 2.6, 3.8 and 4.9 times greater, respectively, than the highest dose of the previous
study. As rapid mortality in three out of five mice was observed in the previous study, the deaths are likely to be due to the methodology used rather than the shellfish toxins. To convert animal data to that used in a human risk assessment, a 100-fold safety factor is required. After applying this safety factor, the dose rates used in the current study were 3.5, 5.0 and 6.5 times greater, respectively, than the acute reference dose for each toxin type set by the European Union. Furthermore, it has previously been proposed that tetrodotoxin be included in the paralytic shellfish poisoning suite of toxins. If this were done, the highest dose rate used in this study would be 13 times the acute reference dose. This
study suggests that the previous 28-day
trial was flawed and that the current paralytic shellfish toxin regulatory limit is fit for purpose. An additional study, feeding mice a diet laced with the test compounds at higher concentrations than those of the current experiment, would be required to comment on whether the current paralytic shellfish toxin regulatory limit should be modified.