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

我们必须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于造成不利影响的化学品浓度。大量的化学品在商业上往往需要在化学品风险评估的预测技术的应用。PI的研究计划的长期愿景是发展可靠地预测人类和野生动物暴露于化学品的能力，这取决于两个信息：化学品的分子结构和使用性质。对于从体内缓慢消除的生物累积化学品，达到有毒组织浓度的可能性特别高。直到最近，人们还认为只有对生物转化有抗性的疏水性有机化合物（HOCs）才能被足够缓慢地消除，从而发生有效的生物积累。然而，最近的研究表明，至少有一些离子源有机化学品（IOCs）具有很大的生物累积潜力，我们目前可用于生物累积评估的预测工具是针对中性HOCs开发的，在很大程度上不适合IOCs。然而，IOC构成了商业上可获得的化学品的很大一部分。目前，缺乏评估国际奥委会生物累积性的定量工具，严重阻碍了全世界有效的化学品管理。因此，我们建议（一）以新颖和有见地的方式开发、评估和应用一套基于相关热力学和动力学现象的机械处理的HOCs和IOCs生物累积模型，及（ii）在实验室测量化学性质及生理特性，以便将这些模型参数化。将发展的新模型工具可应用于（i）帮助理解重要污染物组的吸收、分布、代谢和排泄过程以及组织分布（如全氟烷基酸或羟基化多氯联苯），（二）查明对不同物质特别敏感的人群和个人以及野生物种和食物链，（iii）支持人类生物监测“>，以及（iv）用于接触评估和决策支持，例如，关于旨在减少特别脆弱人群接触污染物的有效干预战略的设计和评价。

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.