Trihalomethane Pharmacokinetics and Pharmacodynamics

三卤甲烷药代动力学和药效学

• 批准号: 6340483
• 负责人: MATTHEW K ROSS
• 金额: $ 4.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-17 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6340483
• 关键词: DNA damage; Rodentias; Salmonella typhimurium; adduct; haloalkane; mutagen testing; pharmacokinetics; postdoctoral investigator; tissue /cell culture; water treatment

DESCRIPTION: (Adapted from the Applicant's Abstract): The greatest uncertainties contributing to poor confidence in risk assessments for water disinfection by-products (DBPs) stem from inadequacies in our capability to determine the relevancy to humans of results from experiments using rodents. The need for data and approaches to address this issue is manifold and includes all aspects of rodent to human extrapolation. Significant data gaps remain in this area for the most prevalent DBPs in our drinking water, the trihalomethanes (THMs). While some progress has been made with chloroform (CHCl3), human data fro brominated THMs (BrTHMs) is nonexistent. For example, in order to scale up existing rodent THM physiologically-based pharmacokinetic (PBPK) models for humans, in vitro determinations of THM metabolic rates are needed. It is also essential to determine if the same metabolic pathways are operative in rodents and humans and if metabolic flux through the different pathways is similar.

描述：（改编自申请人的摘要）：最大的不确定性导致对水消毒副产品（DBP）的信心不佳，源于我们能力不足，无法确定使用啮齿动物实验的人与人类相关的结果。解决此问题的数据和方法的需求是多方面的，包括啮齿动物外推的所有方面。在我们的饮用水中最普遍的DBP，Trihalomethanes（THMS）中，该区域仍然存在很大的数据差距。虽然已经通过氯仿（CHCL3）取得了一些进展，但人类数据从THMS（BRTHM）（BRTHMS）不存在。例如，为了扩展现有的基于生理的药代动力学（PBPK）模型，以便在体外确定THM代谢率。还必须确定相同的代谢途径是否在啮齿动物和人类中是可操作的，以及是否通过不同途径的代谢通量相似。