Evaluating lead bioavailability data by means of a physiologically based lead kinetic model.
Evaluating lead bioavailability data by means of a physiologically based lead kinetic model.
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通过基于生理学的铅动力学模型评估铅的生物利用度数据。
DOI：
10.1093/toxsci/29.1.63
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
P. D. Bergstrom
中科院分区：
文献类型：
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作者：
J. Polák;E. O'FLAHERTY;G. B. Freeman;J. Johnson;S. Liao;P. D. Bergstrom
提出了一种生物利用度估计的方法，其中基于生理学的动力学模型的铅动力学是适合同时血液和骨铅浓度暴露于膳食铅一段时间后。同时拟合的优化（仅改变吸收分数）给出了每个治疗组生物利用度分数的最佳估计值。该分析适用于三个独立的研究中，大鼠连续30天的净化饮食含有铅添加醋酸铅，矿山废物污染的测试土壤，或矿山废物本身的数据。分数吸收减少铅摄入量的增加，无论铅的来源，但这种剂量依赖性的幅度是铅源依赖性。当铅摄入量以单位体重表示时，雌雄大鼠对铅的吸收没有差异。在低暴露率（1-2毫克铅/千克/天）下，当将醋酸铅添加到饮食中时，吸收率从4%到5%不等，而在高暴露率（24毫克/千克/天）下，当将受矿山废物污染的试验土壤添加到饮食中时，吸收率为0.24%。将该分析的结果与更常规的分析结果进行比较，其中将骨和血铅浓度分别与连续29天每天静脉注射醋酸铅的大鼠的骨和血铅浓度进行比较，结果表明标准分析未能揭示吸收分数的剂量依赖性。
A method of bioavailability estimation is presented in which a physiologically based kinetic model of lead kinetics is fit simultaneously to blood and bone lead concentrations after a period of exposure to dietary lead. Optimization of the simultaneous fit, varying only fractional absorption, gives the best estimate of fractional bioavailability for each treatment group. The analysis was applied to data from three separate studies in which rats were fed for 30 consecutive days purified diets containing lead added as lead acetate, mine waste-contaminated test soils, or mine waste itself. Fractional absorption decreased as lead intake increased, regardless of the source of the lead; but the magnitude of this dose dependence was lead source-dependent. There were no differences in lead absorption by male and female rats when lead intake was expressed per unit body weight. Fractional absorption varied from 4 to 5%, at low exposure rates (1-2 mg lead/kg/day) when lead acetate was added to the diet, to 0.24% at a high exposure rate (24 mg/kg/day) when a mine waste-contaminated test soil was added to the diet. Comparison of the results of this analysis with the results of a more conventional analysis, in which the bone and blood lead concentrations were separately compared with bone and blood lead concentrations in rats given daily injections of lead acetate intravenously for 29 consecutive days, demonstrated that the standard analysis failed to reveal the dose dependence of fractional absorption.