Dose-dependent kinetics of inhaled styrene in man

One female and one male volunteer were exposed to styrene vapour (2 h; 50 W) at four different concentrations (26, 77, 201 and 386 ppm). Styrene levels were measured in arterialized capillary blood during and after exposure by head-space gas chromatography, and the levels of mandelic acid in urine were analysed by high-performance liquid chromatography. Non-linear relationships between the level of exposure to styrene and the concentration of styrene in arterial blood and 0-5 h cumulative excretion of mandelic acid indicated metabolic saturation. A physiologically based pharmacokinetic model was used to estimate the maximum metabolic rate (Vmax) of styrene from data on blood styrene. According to the model, the Vmax is 2.9 mmol/h, and metabolic saturation occurs at concentrations of 100-200 ppm styrene, depending on the level of physical activity. To our knowledge, this is the first time that dose-dependent kinetics of styrene has been shown in humans.