Confounding factors in biological monitoring of exposure to organic solvents.

Some environmental and physiological factors that affect the toxicokinetic behaviors of organic solvents were examined using a physiologically based pharmacokinetic model developed for trichloroethylene (TRI). The conclusions are as follows: 1) Body fat content substantially affects the kinetic behavior of TRI: the TRI concentration in blood and the urinary excretion rate of its metabolites are higher in slim men than in obese men during exposure, but these parameters eventually become higher in obese men. 2) There is a sex difference in the pharmacokinetic profiles of TRI. Although retention of TRI in the body is greater in men than in women, the blood concentration of TRI in women is higher than in men 16 hours after exposure. 3) Because of increased pulmonary ventilation and cardiac output, physical activity (workload) during exposure greatly increases the blood concentration of TRI and the urinary excretion of its metabolites, whereas the activity after exposure has only a marginal influence. 4) Ethanol-induced inhibition of TRI metabolism causes a marked change in the kinetic behavior when the TRI exposure level is low, whereas enzyme induction by ethanol significantly affects the kinetics only when the exposure concentration is high. The effect of enzyme induction differs from compound to compound. Whether the compound concerned is a perfusion-limited substrate (TRI, for example) or a capacity-limited substrate (1,1,1-trichloroethane, for example) determines the extent of the effect. 5) Metabolic interaction between solvent vapors inhaled simultaneously may not become apparent until the exposure level increases to a degree that will overload the enzyme capacity.