A chemical thermodynamics-based approach to quantifying contaminant exposure

这笔赠款将支持一个独特的基础研究计划，该计划建立在化学热力学原理的基础上，以推进化学品暴露评估，特别是对污染物生物放大作用的理解。 生物放大作用是生物体体内污染物的脂质标准化浓度高于其所吃食物中普遍存在的浓度的过程。这可以说是最强有力的污染物放大过程;即使是少量的排放和相对较低的环境浓度，也可能导致生物放大污染物的高内部暴露。由于伦理方面的考虑限制了可以进行的调查类型，因此对人类和野生动物物种的生物放大作用的可靠的机械理解一直是难以捉摸的。我们将采用创新方法，将联合收割机非侵入性或微创分析化学方法与动力学建模相结合，进行一系列研究，以阐明与饮食、消化和污染物相关的因素如何影响生物放大作用。我们将使用基于有机硅的平衡装置来量化成对食物和粪便样本中污染物的能力，从而可以估计野生动物物种和人类的生物放大潜力。我们将比较喂食相同饮食的不同食肉动物的生物放大潜力，调查北极熊在分解代谢和合成代谢阶段生物放大的季节性变化，并量化摄入不可消化脂肪替代品和微塑料引起的污染物生物放大潜力的下降。依靠人类志愿者，我们将进一步研究由不同消化效率引起的生物放大潜力的个体间差异，例如受肠道微生物组的影响，以及由不同饮食组成引起的生物放大差异。通过将实验结果纳入食物链生物累积模型，并将这些模型与全球范围的环境归宿和迁移计算联系起来，我们将确定面临最高程度接触特定有机污染物危险的陆地和海洋野生动物种群，即生物放大物质金矿中的全球金丝雀。我们将进一步使用模型来估计人类食物消化和同化能力的变异性对人群中暴露生物标志物（例如血液中生物放大污染物的浓度）测量变异性的影响。虽然生物累积性评估是有效的化学品管理的核心，但判断生物放大作用的经验基础严重偏向于鱼类和实验室动物。通过以前所未有的方式对生物放大作用进行非侵入性研究，我们将通过生成关于最易受生物放大物质危害的生物体的信息，大大加强生物累积性评估。

This grant will support a unique program of basic research that builds on the principles of chemical thermodynamics to advance chemical exposure assessment in general and the understanding of contaminant biomagnification in particular. Biomagnification is the process through which organisms can have higher lipid-normalized concentrations of contaminants in their bodies than are prevalent in the food they eat. It is arguably the most potent contaminant amplification process; even small emissions and relatively low environmental concentrations can lead to high internal exposure to biomagnifying contaminants. Because ethical considerations limit the type of investigations that can be conducted, a solid mechanistic understanding of biomagnification in humans and wildlife species has been elusive. Adopting innovative approaches that combine non-invasive or minimally invasive analytical chemistry methods with kinetic modelling, we will conduct a series of studies to elucidate how factors related to diet, digestion and contaminants influence biomagnification. We will use silicone-based equilibrium devices to quantify the capacity of paired food and feces samples for contaminants, which allows for an estimation of biomagnification potential in wildlife species and humans. We will compare the biomagnification potential of different carnivores being fed the same diet, investigate seasonal changes in the biomagnification of polar bears during catabolic and anabolic phases, and quantify the decrease in the biomagnification potential for contaminants caused by the ingestion of non-digestible fat substitutes and microplastics. Relying on human volunteers we will further study interindividual differences in biomagnification potential caused by different digestion efficiencies, e.g. influenced by the gut microbiome, and the differences in biomagnification caused by variable diet composition. By integrating the experimental findings into food chain bioaccumulation models and linking those models with global scale environmental fate and transport calculations, we will identify the terrestrial and marine wildlife populations that are in danger of experiencing the highest exposure to particular organic contaminants, i.e. the global canaries in the goldmine for biomagnifying substances. We will further use models to estimate the influence of the variability in human food digestion and assimilation capabilities on the measured variability in biomarkers of exposure (e.g. concentrations of biomagnifying contaminants in blood) within a population. Whereas bioaccumulation assessment is central to effective chemical management, the empirical basis for judging biomagnification has been heavily biased towards fish and lab animals. By studying biomagnification non-invasively in ways that had never been possible before, we will greatly enhance bioaccumulation assessment through generating information on those organisms most at risk from biomagnifying substances.