Theoretical and Experimental Approaches to Describe the Chemodynamics of Hydrophobic Organics, Ionogenic Organics and Methyl Mercury in the Food Chain

我们必须能够评估与使用有机化学品有关的风险。其中一个风险是人类和野生动物暴露在会产生不良影响的高浓度化学物质中。商业上大量的化学品往往需要在化学品风险评估中应用预测技术。PI研究计划的长期愿景是发展可靠预测人类和野生动物接触时变化学物质的能力，这两项信息是：化学物质的分子结构和使用性质。达到有毒组织浓度的可能性特别高，因为生物蓄积性化学物质从体内缓慢消除。直到最近，人们才认为只有耐生物转化的疏水性有机化合物（hoc）才能被清除得足够慢，以实现有效的生物积累。然而，最近发现至少一些离子源性有机化学品（IOCs）具有巨大的生物蓄积潜力。我们目前可用于生物积累评估的预测工具是为中性hoc开发的，在很大程度上不适合ioc。然而，国际石油公司占据了商用化学品的很大一部分。目前，缺乏定量工具来评估ioc的生物积累，严重阻碍了世界范围内有效的化学品管理。因此，我们建议(i)基于相关热力学和动力学现象的机械处理，以新颖而有见地的方式开发、评估和应用hoc和ioc生物积累模型工具箱，以及（ii）对这些模型参数化所需的化学性质和生理特征进行实验室测量。将开发的新建模工具可用于（一）帮助了解重要污染物类别（如全氟烷基酸或羟基化多氯联苯）的吸收、分布、代谢和排泄过程以及组织分布，（二）确定对不同物质具有特别高暴露敏感性的人群和个人以及野生动物物种和食物链，（三）支持人体生物监测；（四）提供接触评估和决策支持，例如设计和评价旨在减少特别是弱势群体接触污染物的有效干预战略。

It is imperative that we can assess the risk that is associated with the use of organic chemicals. One such risk is that humans and wildlife are exposed to concentrations of chemicals that cause adverse effects. The huge number of chemicals in commerce often necessitates the application of prediction techniques in chemical risk assessment. The long-term vision of the PI's research program is to develop the capability to reliably predict time-variant chemical exposure of humans and wildlife from two pieces of information: the chemical's molecular structure and the nature of its use.The possibility of reaching toxic tissue concentrations is particularly high for bioaccumulative chemicals with slow elimination from the body. Until recently, it was believed that only hydrophobic organic compounds (HOCs) resistant to biotransformation are eliminated sufficiently slowly for efficient bioaccumulation to occur. However, more recently it was revealed that at least some ionogenic organic chemicals (IOCs) exhibit substantial bioaccumulation potential.The prediction tools we currently have available for bioaccumulation assessment were developed for neutral HOCs and are largely unsuited for IOCs. Yet, IOCs constitute a huge fraction of commercially available chemicals. The dearth of quantitative tools for the bioaccumulation assessment of IOCs is presently a serious obstacle to effective chemical management worldwide. We therefore propose (i) to develop, evaluate and apply in novel and insightful ways a toolbox of bioaccumulation models for HOCs and IOCs based on a mechanistic treatment of the relevant thermodynamic and kinetic phenomena, and (ii) to perform laboratory measurement of chemical properties and physiological characteristics required for the parameterization of such models.The new modeling tools that will be developed can be applied (i) to aid in the understanding of absorption, distribution, metabolism, and excretion processes and of the tissue distribution of important groups of contaminants (such as perfluorinated alkyl acids or hydroxylated polychlorinated biphenyls), (ii) to identify humans populations and individuals as well as wildlife species and food chains with particularly high exposure susceptibility to different substances, (iii) in support of human biomonitoring ">, and (iv) for exposure assessment and decision support, e.g. regarding the design and evaluation of effective intervention strategies aimed at reducing contaminant exposure of particularly vulnerable populations.