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在会造成不良影响的化学品浓度中。商业中大量的化学品经常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根据两条信息：化学物质的分子结构和使用性质，开发可靠地预测人类和野生动物接触时变化学物质的能力。对于体内消除缓慢的生物累积化学物质，达到有毒组织浓度的可能性尤其高。直到最近，人们一直认为，只有对生物转化具有抵抗力的疏水有机化合物(HOCs)才能以足够慢的速度消除，从而实现有效的生物积累。然而，最近发现，至少有一些离子型有机化合物(IOCs)具有很大的生物累积潜力。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一大部分。目前，缺乏用于评估海委会生物积累的量化工具是全世界有效管理化学品的严重障碍。因此，我们建议(I)基于对相关热力学和动力学现象的机械处理，以新颖和有见地的方式开发、评估和应用HOCs和IOCs的生物累积模型工具箱，以及(Ii)对此类模型的参数化所需的化学性质和生理特性进行实验室测量。将开发的新的建模工具可用于(I)帮助理解重要污染物组(如全氟烷基酸或羟基多氯联苯)的吸收、分布、代谢和排泄过程以及组织分布，(2)确定对不同物质具有特别高暴露敏感性的人类种群和个人以及野生动物物种和食物链，(3)支持人类生物监测“&GT；以及(4)暴露评估和决策支持，例如，关于设计和评价旨在减少特别脆弱人群污染物暴露的有效干预战略。

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.