急性毒性試験の近代化によるテトロドトキシンの中枢影響評価

抄録

In recent years, tetrodotoxin (TTX) has drawn international attention as a shellfish toxin. “Mouse Unit (MU)” has been used for a long period for evaluation of shellfish toxin in Japan; MU is determined by “Mortality” considering the lethal time in an acute toxicity study (ATS). On the other hand, EFSA has reported evaluation of TTX in which the “Apathy” was used as endpoint (EP) in an ATS. ATSs are also essential for classification and labeling of substances, but are criticized both scientific and ethical grounds; not to provide information on possible target organs and possible mechanisms of toxicity, and Mortality is not a desirable EP from the viewpoint of animal welfare. It is considered an excellent way to improve ATSs by accurately measuring and quantifying the signs of toxicity across multiple items and creating reasonable criteria for the acute toxicity of a substance. However, this will be a complicated and expensive test compared to ATSs, which uses Mortality as the endpoint. For modernization of ATSs, we are focusing on vital signs and wearable devices with cutting-edge sensors, furthermore, to consider validity of the vital signs for acute toxicity, comprehensive gene expression analysis of central nervous system was conducted. In other words, it is the development of a test method that obtains vital signs from animals corresponding to tests that human acutely poisoned patients undergo in emergencies. In this symposium, we would like to share the effect on central nervous system of TTX as a case evaluated by modernization of ATS.