O'Flaherty E J
Department of Environmental Health, University of Cincinnati College of Medicine, Ohio, USA.
Environ Health Perspect. 1998 Dec;106 Suppl 6(Suppl 6):1495-503. doi: 10.1289/ehp.98106s61495.
A physiologically based model of lead kinetics in children and adults has been developed and tested. The premises on which the physiologically based model is founded are reviewed in this paper. Because 95% or more of the body burden of lead in adults is found in the bone, bone metabolism is central to the model. Bone volumes are expressed as functions of body weight. Bone formation and resorption rates are estimated from human studies of stable labeled calcium kinetics. Cortical and trabecular bone are modeled separately, with their surface-to-volume ratios taken into account. Standardized growth curves are used to relate body weight to age. Other model features such as organ volumes and physiologic functions are related to body weight based on measurements made in human subjects over a range of ages. Calibrations of the model to two human data sets are shown, and two applications to specific research questions are illustrated. A brief comparison of the structure of this model with that of the Leggett model, and a comparison of the output of this model with that of the integrated exposure uptake biokinetic model of the U.S. Environmental Protection Agency, are also included.
已开发并测试了一个基于生理学的儿童和成人铅动力学模型。本文回顾了构建该基于生理学模型的前提条件。由于在成年人中,95%或更多的铅身体负荷存在于骨骼中,因此骨骼代谢是该模型的核心。骨体积表示为体重的函数。骨形成和再吸收率是根据对稳定标记钙动力学的人体研究估算得出的。皮质骨和小梁骨分别建模,并考虑了它们的表面积与体积比。使用标准化生长曲线将体重与年龄联系起来。基于在一系列年龄段的人体受试者中所做的测量,其他模型特征(如器官体积和生理功能)与体重相关。展示了该模型针对两个人体数据集的校准情况,并举例说明了该模型在特定研究问题中的两个应用。还包括了此模型与莱格特模型结构的简要比较,以及此模型与美国环境保护局综合暴露吸收生物动力学模型输出结果的比较。