Physiologically-relevant bioaccessibility measurements of inorganic contaminants

加拿大有22,000多个受污染的地点[1]，暴露在土壤污染物中对人类健康构成风险[2]。传统上，这些风险是根据偶然摄入的土壤中污染物的总浓度来评估的，但这可能高估了剂量，因为不可溶部分通过消化系统，而不被吸收到体循环。体内测试可能会提供与生理相关的数据，但成本高昂，而且存在伦理问题。取而代之的是，生物可及性测试测量可供人体吸收的污染物部分，从而提供与生理相关的测量。当考虑到生物可获得性时，补救工作可以针对已确定风险的领域。这种方法可以在保护敏感环境的同时显著节省成本，否则敏感环境将受到过度保守的补救活动的不必要干扰。在这一领域最新进展的基础上，我们建议开发准确反映生理条件并产生代表性结果的生物可及性测试。该计划的长期目标是为风险评估员和政策制定者提供完全表征的、与生理相关的生物可获得性数据，以衡量土壤污染物(如砷和银和镍合金纳米颗粒等新产品)的暴露情况。为此，我们将重点关注以下短期目标：(A)胃肠道混合参数的计算流体动力学模拟。这些模型将(B)在体外应用，以适当地模拟消化运动。在这些结果的基础上，我们将(C)调查混合污染物，如多环芳烃(PAHs)对土壤中砷的影响，并调整生物可及性测试液的化学成分。最后，我们建议(D)使用人工多孔介质研究胶体和小颗粒的传输和上皮吸收，这可能会增强数据的可靠性，特别是在无法与体内结果进行比较的情况下。最终，这项研究计划的愿景是淘汰体内测试。该计划将培训高素质的工程师(2名博士，3名硕士，5名UG)，为他们提供严格的培训，以发展坚实的专业知识，评估受污染的土壤的风险。这项拟议研究的结果直接适用于保护人类健康，并将指导加拿大人、环境监管机构和风险评估人员对已确定的风险区域进行有针对性的补救，从而减少对受污染场地的干扰，并提高成本效益。

There are more than 22,000 contaminated sites in Canada [1], and exposure to soil contaminants poses risks to human health [2]. These risks are traditionally evaluated based on the total concentration of a contaminant in soil taken up from incidental ingestion, but this may overestimate the dose because non-soluble portions move through the digestive system without being absorbed into systemic circulation. In-vivo tests may provide physiologically-relevant data, but are costly and ethically problematic. Instead, bioaccessibility tests measure the portion of a contaminant available for absorption by the human body, and thus provide a physiologically-relevant measurement. When bioaccessibility is factored in, remediation efforts can target areas where risks have been identified. This approach allows for significant cost savings while protecting sensitive environments, which would otherwise be unnecessarily disturbed by overconservative remediation activities. Building on recent advances in this field, we propose to develop bioaccessibility tests that accurately reflect physiological conditions and yield representative results. The long-term goal of this program is to produce fully characterized and physiologically-relevant bioaccessibility data for risk assessors and policy makers to measure exposure to soil contaminants, (e.g. arsenic and new products, such as silver and nickel-alloy nanoparticles). To this end, we will focus on the following short-term objectives: (A) computational fluid dynamic simulations of gastrointestinal mixing parameters. These models will (B) be applied in-vitro to appropriately simulate digestive movement. Expanding on these results, we will (C) investigate the effects of mixed contaminants, such as polycyclic aromatic hydrocarbons (PAHs) on arsenic in soils, and adjust the chemical make-up of bioaccessibility test fluids. Finally, we propose to (D) study transport and epithelial absorption of colloids and small particles using an artificial porous medium, which may enhance the reliability of the data, especially in cases where comparisons with in-vivo results are not available. Ultimately, the vision of this research program is to render in-vivo tests obsolete.This program will train highly qualified engineers (2 PhD, 3 MSc, 5 UG), providing them with rigorous training to develop a solid expertise in the evaluation of risks from contaminated soils. The outcome of this proposed research is directly applicable to protecting human health, and will guide Canadians, environmental regulatory agencies, and risk assessors toward a targeted remediation of identified risk areas, resulting in less intrusive and more cost-effective redevelopment of contaminated sites.