Trihalomethane Pharmacokinetics and Pharmacodynamics

产品说明：（改编自申请人摘要）：导致水消毒副产物（DBP）风险评估信心不足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。解决这一问题的数据和方法的需求是多方面的，包括啮齿动物到人类外推的所有方面。对于我们饮用水中最常见的DBP，即三卤甲烷（THMs），这一领域仍存在重大数据缺口。虽然在氯仿（CHCl3）方面取得了一些进展，但溴化THMs（BrTHMs）的人体数据尚不存在。例如，为了扩大现有的用于人类的啮齿动物基于THM生理学的药代动力学（PBPK）模型，需要体外测定THM代谢速率。同样重要的是，要确定是否相同的代谢途径在啮齿动物和人类中起作用，以及通过不同途径的代谢通量是否相似。

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.