Evaluation of stable isotope-labeled probes in the study of solvent pharmacokinetics in human subjects.
Morgan-MS; Dills-RL; Kalman-DA
Int Arch Occup Environ Health 1993 Jan; 65(1):S139-S142
The pharmacokinetics of stable isotope labeled probes used in the study of toluene (108883) were examined in human subjects. Twenty one men inhaled 100 parts per million of an equal molar mixture of unlabeled and fully deuterated toluene for 2 hours. Washout kinetics for both compounds were then monitored for 4 days by measuring the compounds and their metabolites in alveolar air, blood, and urine. While both compounds exhibited three phase elimination kinetics in air and blood, the third phase was not always definable for unlabeled toluene because of concurrent uncontrolled environmental exposure. Concentrations of unlabeled and fully deuterated toluene in alveolar air and blood were well correlated when data from only the first two phases were considered. A satisfactory fit could be obtained in all cases despite large variations in model coefficients among individuals. The authors conclude that the data support use of deuterated toluene as a suitable probe for the study of toluene kinetics. Further experiments are needed to determine whether correlations between unlabeled and deuterated toluene for the third phase are influenced by an isotope effect.
NIOSH-Publication; NIOSH-Grant; Training; Biological-monitoring; Inhalation-studies; Humans; Toluenes; Pharmacodynamics; Isotope-effect; Analytical-methods; Analytical-models; Solvents; Radioisotopes
Environmental Health University of Washington Environmental Health Dept Seattle, Wash 98195
International Archives of Occupational and Environmental Health
University of Washington, Seattle, Washington