Trihalomethane Pharmacokinetics and Pharmacodynamics

三卤甲烷药代动力学和药效学

• 批准号: 6525336
• 负责人: MATTHEW K ROSS
• 金额: $ 4.81万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-17 至 2004-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6525336
• 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：（改编自申请人摘要）：导致水消毒副产物（DBPs）风险评估可信度低的最大不确定性源于我们确定啮齿动物实验结果与人类相关性的能力不足。需要的数据和方法来解决这个问题是多方面的，包括所有方面的啮齿动物到人类的外推。关于我们饮用水中最普遍的dbp三卤甲烷（THMs），在这一领域仍存在重大数据缺口。虽然氯仿（CHCl3）已经取得了一些进展，但溴化THMs （BrTHMs）的人体数据尚不存在。例如，为了扩大现有的啮齿动物THM基于人体生理的药代动力学（PBPK）模型，需要体外测定THM的代谢率。确定啮齿动物和人类是否有相同的代谢途径，以及通过不同途径的代谢通量是否相似，也很重要。