O'Flaherty E J
Department of Environmental Health, University of Cincinnati College of Medicine, Ohio 45208-0056, USA.
Toxicol Appl Pharmacol. 1995 Apr;131(2):297-308. doi: 10.1006/taap.1995.1072.
A physiologically based model of lead absorption and disposition, previously developed and validated for adults, has been tested and calibrated for children. The model was modified to incorporate additional information on the age dependence of bone formation rate and to take into account increasing localization of bone modeling activity with age. A bone volume characterized by mature bone metabolic activity increases from zero at birth to the total bone volume by young adulthood. Bone formation rate is high from childhood through adolescence, with peaks at birth and around puberty. Bone resorption rate keeps pace at a rate that allows the orderly increase of bone mass. In general, the model reproduces childhood blood lead observations well, except in instances where lead is ingested at very high concentrations. Both bone and blood lead concentration are labile during early childhood because of the high rate of bone turnover. They respond rapidly to increases in lead exposure, and decrease almost as rapidly to near-preexposure concentrations when exposure returns to background levels. As the child grows, fractional bone formation and resorption rates decline and total bone lead turnover becomes more sluggish. From the time of peak bone mineralization rate in adolescence into early adulthood, the rate of bone turnover drops dramatically and the ability to reverse bone lead accumulation relatively rapidly is lost.
一个先前已针对成年人开发并验证的基于生理学的铅吸收与分布模型,现已针对儿童进行了测试和校准。该模型经过修改,纳入了关于骨形成率年龄依赖性的更多信息,并考虑到随着年龄增长骨建模活动的局部化增加。以成熟骨代谢活性为特征的骨量从出生时的零增加到青年期的总骨量。从儿童期到青春期骨形成率都很高,在出生时和青春期前后达到峰值。骨吸收率以允许骨量有序增加的速率保持同步。总体而言,该模型能很好地再现儿童期血铅观测结果,除非铅以非常高的浓度摄入。由于幼儿期骨转换率很高,骨铅和血铅浓度在幼儿期都不稳定。它们对铅暴露的增加反应迅速,当暴露恢复到背景水平时,几乎同样迅速地降至接近暴露前的浓度。随着儿童成长,骨形成和吸收的分数率下降,总骨铅周转率变得更加缓慢。从青春期骨矿化率峰值到成年早期,骨转换率急剧下降,相对迅速逆转骨铅积累的能力丧失。