Effects driven assessment and management of complex operating sites

加拿大各地有许多复杂的运营地点。这些地点含有各种潜在的令人担忧的化学品，其中许多是由于土壤和水中的部分分解而产生的。对于这些化学品中的大多数，都没有明确定义的安全限度或详细的毒理学信息。这项合作研究和开发提案的目的是开发一种方法来评估定义不明确的污染物的复杂混合物的数量、环境移动、毒性和风险。我们将与我们的工业合作伙伴IPCO、Amec Foster Wheller和马尼托巴省自然保护局密切合作，使用影响驱动的评估来评估复杂运营地点的分布和风险。效果导向评估使用非基于动物的毒性测试，例如肝细胞系，来评估污染物混合物在土壤、水和空气中的毒性程度。在这里，我们建议扩展这种影响驱动的评估，以开发一个模型，说明这些复杂的毒物混合物如何在土壤、空气和水中移动。然后，我们将使用各种细胞系，例如肠、肝、肺和肾细胞系，以确定混合物中哪些成分毒性最大，以及它们如何造成毒性。使用鱼类动物模型，然后我们将使用标准的动物设计来确认这种毒性模式。最后，我们将通过比较细胞系对毒物混合物的反应与相同细胞系对30种参考毒物的反应来估计这种复杂的毒物混合物对人类构成的风险。这些参考毒物已经有与它们相关的动物数据，因此我们将能够从我们的混合物中读取这些参考毒物，以推断人类的安全暴露水平。在这个项目结束时，我们将为加拿大开发出一种方法来评估与复杂运营地点相关的风险。

There are many complex operating sites located across Canada. These sites contain a wide variety of chemicals of potential concern, many of which have arisen due to partial breakdown in the soil and water. For most of these chemicals, there are no well-defined safe limits or detailed toxicological information. The purpose of this Collaborative Research and Development proposal is to develop a method to assess the amount, environmental movement, toxicity and risk of complex mixtures of ill-defined pollutants. Working closely with our industrial partners, IPCO, Amec Foster Wheller and the Manitoba Conservation Authority, we will use effects driven assessment to estimate the distribution and risk across a complex operating site. Effects driven assessment uses non-animal based toxicity tests, for example liver cell lines, to estimate how toxic a pollutant mixture is in soil, water and air. Here we propose to extend this effects driven assessment to develop a model of how these complex mixtures of toxicants move through the soil, air and water. Following this, we will then use a variety of cell lines, for example intestinal, liver, lung and kidney cell lines, to identify what components of the mixture are most toxic and how do they cause toxicity. Using a fish animal model, we will then confirm this mode of toxicity using a standard animal design. Finally, we will estimate the risk posed to humans by this complex mixture of toxicants by comparing the response of cells lines to the toxicant mixture to the same cell lines' response to a collection of 30 reference toxicants. These reference toxicants already have animal data associated with them, and thus we will be able to read across from our mixture to these reference toxicants to infer safe exposure levels for humans. At the conclusion of this project, we will have developed a method for Canadian's to assess the risk associated with complex operating sites.