Predictable "individual differences" in uptake and excretion of gases and lipid soluble vapours simulation study

Abstract

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).