Biotransformation of commercial chemicals in food-webs

该研究计划旨在提高对商业化学品的环境命运和影响的认识，并开发更好的方法来测量和评估化学品暴露和对野生动物和人类的风险，以支持国家和国际保护人类和环境健康的举措。以前的研究涉及控制化学品在水生和陆生食物网中生物累积的物理化学因素的作用。拟议的研究调查生物转化对食物网中生物积累的作用。缺乏衡量生物转化率的方法以及随后缺乏大多数商业物质的生物转化数据，现已被确定为目前正在对环境中化学品的归宿和影响进行评估的一个关键科学知识空白。这项研究的目标是：（一）制定在体外和体内研究中确定化学品生物转化率的方法;（二）调查在体外和体内研究中测得的生物转化率与实地生物转化率之间的关系;（三）制定和测试可用于监管目的的代谢物质生物累积数学模型。该研究包括4个项目，涉及一组常见的化学物质。项目1包括开发一种新型的体外给药系统，以测量肝脏和肠匀浆中极疏水物质的体外生物转化率。项目2开发和应用测量大鼠和虹鳟鱼体内生物转化率的方法。项目3涉及开发一个药代动力学模型，用于关联体外和体内生物转化率。项目4开发和测试食物链生物累积 进行生物转化的物质的模型。这项研究产生的好处：（一）野生动物和人类健康（通过识别有害物质），（二）化学品制造商（通过改善监管化学品评估协议），（三）环境咨询业（通过建立生物转化测试协议的专门知识，以及（四）支持加拿大政府在化学品管理的国家和国际倡议。

This research program aims to enhance knowledge of the environmental fate and effects of commercial chemicals and to develop better methods for measuring & assessing chemical exposure and risks to wildlife & humans in support of national and international initiatives to protect human and environmental health. Previous research involved the role of physical-chemical factors controlling the bioaccumulation of chemicals in aquatic and terrestrial food-webs. The proposed research investigates the role of biotransformation on bioaccumulation in food-webs. The lack of methods to measure biotransformation rates and the subsequent lack of biotransformation data for most commercial substances have now been identified as a key scientific knowledge gap in the on-going evaluation of the fate and effects of chemicals in the environment. The goal of the research is (i) to develop methods for determining the rate of biotransformation of chemicals in in-vitro and in-vivo studies and (ii) to investigate the relationship between biotransformation rates measured in in-vitro and in-vivo studies and in the field and (iii) to develop and test mathematical bioaccumulation models for metabolizing substances that can be used for regulatory purposes. The research includes 4 projects involving a common set of chemical substances. Project 1 includes the development of a novel in-vitro dosing system to measure in-vitro biotransformation rates of extremely hydrophobic substances in liver and intestinal homogenates. Project 2 develops and applies methods for measuring in-vivo biotransformation rates in rats and rainbow trout. Project 3 involves the development of a pharmacokinetic model for relating in-vitro and in-vivo biotransformation rates. Project 4 develops and tests a food-chain bioaccumulation model for substances that undergo biotransformation. This research produces benefits to (i) wildlife and human health (by identifying harmful substances), (ii) chemical manufacturers (by improving regulatory chemical evaluation protocols), (iii) environmental consulting industry (by establishing know-how on biotransformation test protocols, and (iv) supports the Canadian government in their national and international initiatives of chemical stewardship.