慢性暴露低濃度塑化劑DEHP對免疫、肥胖、及帕金森氏症之毒性效應及其分子調控機制

2019-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/654844摘要：「塑化劑」因民眾廣泛且持續於日常生活中暴露，為全球及我國重視的「食品安全」及健康的議題。過去研究指出，相較於美國及歐盟，國人於生活中經常接觸含塑化劑之塑膠產品或受塑化劑污染之食品，導致暴露劑量偏高。此外，目前我國對塑化劑每人每日耐受量參考值規範仍較高。更多及完整的塑化劑毒理資訊，將有助於更準確的評估食品健康風險。塑化劑雖然不會長時間滯留於人體中，但因頻繁的暴露，尤其易於PVC容器中釋出，然而「慢性低濃度暴露塑化劑」是否構成健康危害，尤其對先天免疫、肥胖及引起帕金森氏症相關的影響，目前仍所知有限。本研究提出三年的計畫，針對國人最常暴露的塑化劑：DEHP，利用廣泛應用於生物醫學研究的C. elegans為模式生物，透過「低濃度慢性暴露塑化劑DEHP」的實驗設計及不同暴露情境，探討慢性暴露塑化劑DEHP對於先天免疫、肥胖以及帕金森氏症的毒性效應與老化的關係，並深入探討其分子調控機制。本研究成果將提供更多及詳盡的慢性暴露塑化劑健康危害資訊，將能提供政府日後制定食品容器及其製程中，塑化劑濃度規範的參考依據及每人每日耐受量參考值之參考，以保障國人日常食品安全。 <br> Abstract: Phthalates exposure frequently occurs in our daily life. Therefore, phthalates contamination has been an emerging global “food safety” concern as well as in Taiwan. Previous study has reported that the phthalates exposure levels in the Taiwanese population were much higher than those in EU and USA. In addition, the current recommended Tolerable Daily Intake (TDI) values for phthalates in Taiwan are higher than those in EU and USA. More and accurate toxicity data for phthalates will be helpful to establish an accurate health risk assessment. Phthalates are metabolized and excreted from the body, however, it is likely that human beings are chronically exposed to low concentration of phthalates due to the fact that phthalates are widely used and it may migrate from food packaging into food. However, whether chronic low concentrations exposure to phthalates DEHP adversely affect innate immunity, obesity, and Parkinson`s disease is not clear. Herein, this 3-year project plans to investigate toxicity of the most frequently exposed di-(2-ethylhexyl) phthalate (DEHP) using the nematode Caenorhabditis elegans (C. elegans) as a model organism. In particular, toxicity of chronic low concentration exposure to DEHP on innate immunity, obesity, and Parkinson`s disease and their relationships with aging will be discussed. Furthermore, the underlying molecular mechanisms will be deciphered. Results from this research will advance our knowledge on potential health hazards by chronic DEHP exposure. This could be used as valuable information for Taiwanese government while setting up the regulations for phthalates levels and TDI reference values. Ultimately, results from this research may contribute to current health risk assessment and facilitate better food safety policies.食品安全塑化劑DEHP老化低濃度慢性暴露先天免疫肥胖帕金森氏症C. elegansfood safetyphthalate DEHPaginglow concentrations chronic exposureinnate immunityobesityParkinson's diseaseC. elegans慢性暴露低濃度塑化劑DEHP對免疫、肥胖、及帕金森氏症之毒性效應及其分子調控機制