Fiserova-Bergerova V, Vlach J, Cassady J C
Br J Ind Med. 1980 Feb;37(1):42-9. doi: 10.1136/oem.37.1.42.
A five-compartment pharmacokinetic model with two excretory pathways, exhalation and metabolism, based on first order kinetics is used to outline the effect of body build, pulmonary ventilation, and lipid content in blood on uptake, distribution, and clearance of low solubility gases and lipid soluble vapours during and after exposure. The model shows the extent that individual differences have on altering uptake and distribution, with consequent changes in blood concentration, rate of excretion, and toxicity, even when variations in these parameters are within physiological ranges. The model is also used to describe the concentration variation of inhaled substances in tissues of subjects exposed to concentrations with permitted excursions. During the same course of exposure, the tissue concentrations of low solubility gases fluctuate much more than tissue concentrations of lipid soluble vapours. The fluctuation is reduced by metabolism of inhaled substance. These conclusions are recommended for consideration whenever evaluating the effect of excursions above the threshold limit values used in the control of industrial exposures (by excursion factors).
基于一级动力学的具有呼气和代谢两种排泄途径的五室药代动力学模型,用于概述体型、肺通气和血液中脂质含量对低溶解度气体和脂溶性蒸气在暴露期间及之后的摄取、分布和清除的影响。该模型显示了个体差异在改变摄取和分布方面的程度,进而导致血液浓度、排泄速率和毒性的变化,即使这些参数的变化在生理范围内。该模型还用于描述暴露于允许波动浓度的受试者组织中吸入物质的浓度变化。在相同的暴露过程中,低溶解度气体的组织浓度波动比脂溶性蒸气的组织浓度波动大得多。吸入物质的代谢可减少这种波动。在评估高于工业暴露控制中使用的阈限值的波动影响(通过波动因子)时建议考虑这些结论。