化学品毒性高通量生物测试与评价技术

马梅

摘 要：针对化学品的生态毒性，以遗传毒性、内分泌干扰物效应和细胞损伤效应为重点， 优化和改进现有的离体生物测试方法，同时构建新的离体测试细胞品系，发展基于生化反应和基于细胞的新的离体测试方法。针对不同生物效应，构建不同离体生物测试技术组合，实现对多个样品特定生物效应的同步检测。发展化学品的高内涵筛选技术，实现对特定化学品多效应同步检测的高内涵离体测试。针对我国实验生物的多元化和代表性差的特点，以我国土著生物为核心选择包括陆生生物、水生生物、土壤生物以及两栖类生物的代表种，根据所选择实验生物目前背景生物学工作基础，选择性开展部分代表性实验生物的实验室培育和繁殖技术，初步实现代表性实验生物模型化，构建化学品的活体生物毒性测试技术。通过测试方法标准化研究，初步形成具有自主知识产权的化学品毒性测试技术体系和相关技术标准；构建能够实现特定毒性效应的高通量、多指标离体测试技术平台和以我国土著生物为核心活体毒性和毒理评价方法和指标体系；对国内市场广泛使用的50种以上工业化学品进行离体毒性测试，并完成相应的分类，并利用活体毒性测试方法和指标对其中具有潜在毒性作用的化学品进行系统评价，确认化学品毒性效应；通过测试方法标准化研究，初步形成具有自主知识产权的化学品毒性测试技术体系和相关技术标准，初步形成部分化学品毒性数据库。有关成果为我国的化学品安全管理提供评估技术支持。

关键词：高通量 生物测试 毒性评价

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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