BILOCATION - Mechanistic approach for estimating and modeling the bioconcentration potential of charged and ionogenic organic chemicals via in vitro, in vivo and in silico methods

BILOCATION - 通过体外、体内和计算机方法估计和模拟带电和离子有机化学品的生物富集潜力的机械方法

• 批准号: 380298548
• 负责人: Professor Dr. Stefan Stolte
• 金额: --
• 依托单位: Faculty of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/380298548?language=en
• 关键词: BILOCATION; Mechanistic; approach; estimating; modeling

The bioconcentration/bioaccumulation potential of chemicals is of highest concern for environmental risk assessment, since it is known to cause far reaching hazards to wildlife and human health. Generally, the experimental measurement of bioconcentration is time consuming, expensive, and due to ethical concerns regarding animal welfare not feasible for large sets of chemicals. Thus prediction models (mainly based on easily determinable physicochemical properties such as the octanol water partition coefficient ) are used for the risk assessment. The existing prediction models are applicable to hydrophobic and polar organic chemicals; however, they often give inappropriate and inaccurate results for ionogenic compounds and permanently charged organic chemicals. This is due to the fact that classical bioconcentration models neither sufficiently consider ion macromolecule interactions nor interactions of cations and anions in solution : both strongly influencing the transport, uptake and bioavailability of ions. The main aim of the proposed project is to understand and predict the interactions of organic ions, and ion pairs in particular, with biological systems and their consequences in terms of bioconcentration. Therefore a mechanistic approach combining in vitro and in vivo tests will be employed to a comprehensive set of charged and ionogenic compounds. The experimental results will provide the basis for establishing meaningful Quantitative Structure Activity Relationships (QSARs) allowing for a reliable estimation of the bioaccumulation potential of ionic species. Considering the fact that around 70 000 compounds already preregistered under REACH are ionogenic or charged chemicals the proposed approach aims to close an urgent knowledge gap that exists in fundamental research as well as in environmental legislation. Protic and aprotic ionic liquids will be the protagonists of this project.

化学品的生物浓缩/生物累积潜力是环境风险评估中最受关注的问题，因为众所周知，它会对野生动物和人类健康造成深远的危害。一般而言，生物浓缩的实验测量费时、昂贵，而且出于对动物福利的伦理考虑，对大量化学品不可行。因此，风险评估使用预测模型（主要基于容易确定的理化性质，如辛醇/水分配系数）。现有的预测模型适用于疏水性和极性有机化学品，然而，他们往往给出不适当的和不准确的结果，离子型化合物和永久带电的有机化学品。这是因为传统的生物浓缩模型既没有充分考虑离子大分子之间的相互作用，也没有充分考虑溶液中阳离子和阴离子之间的相互作用：这两种相互作用都对离子的迁移、吸收和生物利用度产生强烈影响。拟议项目的主要目的是了解和预测有机离子，特别是离子对与生物系统的相互作用及其在生物浓缩方面的后果。因此，结合体外和体内测试的机制方法将被用于一套全面的带电和离子化化合物。实验结果将为建立有意义的定量构效关系（QSAR）提供基础，从而可靠地估计离子物种的生物累积潜力。考虑到已经在REACH下预注册的大约70，000种化合物是离子或带电化学品，拟议的方法旨在弥合基础研究和环境立法中存在的紧迫知识差距。质子和非质子离子液体将是这个项目的主角。