化學品毒性高通量生物測試與評價技術

馬梅

摘 要：針對化學品的生態毒性，以遺傳毒性、內分泌干擾物效應和細胞損傷效應為重點， 優化和改進現有的離體生物測試方法，同時構建新的離體測試細胞品系，發展基于生化反應和基于細胞的新的離體測試方法。針對不同生物效應，構建不同離體生物測試技術組合，實現對多個樣品特定生物效應的同步檢測。發展化學品的高內涵篩選技術，實現對特定化學品多效應同步檢測的高內涵離體測試。針對我國實驗生物的多元化和代表性差的特點，以我國土著生物為核心選擇包括陸生生物、水生生物、土壤生物以及兩棲類生物的代表種，根據所選擇實驗生物目前背景生物學工作基礎，選擇性開展部分代表性實驗生物的實驗室培育和繁殖技術，初步實現代表性實驗生物模型化，構建化學品的活體生物毒性測試技術。通過測試方法標準化研究，初步形成具有自主知識產權的化學品毒性測試技術體系和相關技術標準；構建能夠實現特定毒性效應的高通量、多指標離體測試技術平臺和以我國土著生物為核心活體毒性和毒理評價方法和指標體系；對國內市場廣泛使用的50種以上工業化學品進行離體毒性測試，并完成相應的分類，并利用活體毒性測試方法和指標對其中具有潛在毒性作用的化學品進行系統評價，確認化學品毒性效應；通過測試方法標準化研究，初步形成具有自主知識產權的化學品毒性測試技術體系和相關技術標準，初步形成部分化學品毒性數據庫。有關成果為我國的化學品安全管理提供評估技術支持。

關鍵詞：高通量 生物測試 毒性評價

Abstract： For ecological toxicity of chemicals， genotoxicty， endocrine disrupting and cellular damage effects were mainly studied. The existing in vitro methods related to these toxicology effects were optimized and improved. Meanwhile， new cell lines were constructed and new in vitro tests based on biochemical reaction and cell were developed. In different biological effects， a battery of in vitro tests was built to detect a certain biological effect of several samples at the same time. High content screening technology was applied in chemical screening to detect multiple biological effects of a certain chemical in vitro at the same time. As the experimental organisms is multiple and of poor representative， organisms concluding terrestrial， aquatic， soil and amphibian organisms were chosen as representative species from native organisms in our country. Based on the current biological background of the chosen experimental organisms， partial representative organisms cultivation and reproduction technology were developed. Then modeling of representative organisms were realized initially and in vivo toxicity test technology of chemicals were built. By standardizing research of the test methods， proprietary intellectual property rights based on techniques system of chemical toxicity test and related standards were preliminary formed. High throughput and multi-index technique platforms of in vitro tests were built. And assessment methods and index system of in vivo toxicity tests based on native organisms were established. Toxicity of more than fifty kinds of widely used industry chemicals were analyzed and classified by in vitro test. The chemical of potential toxicity were assessed and confirmed scientific by in vivo toxicity test. By standardizing research of test methods， proprietary intellectual property rights based on techniques system of chemical toxicity test and related standards were preliminary formed. Also， a toxicity database of some chemicals was formed preliminary. Relevant results could provide assessing technique for chemical safety management in our country.

Key Words： High throughput； Bioassay； Toxicity evaluation

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