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The State Of In Vitro Science For Use In Bioaccumulationassessments For Fish

机译:用于鱼类生物蓄积评估的体外科学状况

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Through the concerted evaluations of thousands of commercial substances for the qualities of persistence, bioaccu-mulation, and toxicity as a result of the United Nations Environment Program's Stockholm Convention, it has become apparent that fewer empirical data are available on bioaccumulation than other endpoints and that bioaccumulation models were not designed to accommodate all chemical classes. Due to the number of chemicals that may require further assessment, in vivo testing is cost prohibitive and discouraged due to the large number of animals needed. Although in vitro systems are less developed and characterized for fish, multiple high-throughput in vitro assays have been used to explore the dietary uptake and elimination of Pharmaceuticals and other xenobiotics by mammals. While similar processes determine bioaccumulation in mammalian species, a review of methods to measure chemical bioavailability in fish screening systems, such as chemical biotransformation or metabolism in tissue slices, perfused tissues, fish embryos, primary and immortalized cell lines, and subcellular fractions, suggest quantitative and qualitative differences between fish and mammals exist. Using in vitro data in assessments for whole organisms or populations requires certain considerations and assumptions to scale data from a test tube to a fish, and across fish species. Also, different models may incorporate the predominant site of metabolism, such as the liver, and significant presystemic metabolism by the gill or gastrointestinal system to help accurately convert in vitro data into representative whole-animal metabolism and subsequent bioaccumulation potential. The development of animal alternative tests for fish bioaccumulation assessment is framed in the context of in vitro data requirements for regulatory assessments in Europe and Canada.
机译:通过对联合国环境规划署《斯德哥尔摩公约》的结果,对数千种商业物质的持久性,生物蓄积性和毒性的质量进行了一致的评估,与其他指标相比,显然可获得的生物蓄积性经验数据更少,而且生物蓄积模型并非旨在适应所有化学类别。由于可能需要进一步评估的化学药品的数量,体内测试成本高昂,并且由于需要大量动物而不鼓励这样做。尽管鱼的体外系统尚不完善,并没有针对鱼类进行表征,但已使用多种高通量体外测定法来研究饮食对哺乳动物的药物吸收和对药物及其他异生物的消除。虽然类似的过程决定了哺乳动物物种的生物蓄积性,但对鱼类筛查系统中化学生物利用度的测量方法(如组织切片,灌注组织,鱼胚,原代和永生细胞系以及亚细胞级分的化学生物转化或代谢)的方法综述提出了定量方法鱼和哺乳动物之间存在质的差异。在评估整个生物体或种群时使用体外数据需要一定的考虑和假设,以便将数据从试管到鱼类以及整个鱼类物种进行缩放。同样,不同的模型可能会合并主要的代谢部位(例如肝脏),并通过g或胃肠道系统进行明显的全身代谢,以帮助将体外数据准确地转换为代表性的全动物代谢和后续的生物蓄积潜力。针对鱼类生物蓄积性评估的动物替代测试的开发是在欧洲和加拿大监管评估的体外数据要求的框架内进行的。

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