A compartmental model for the kinetics of mercury vapor in humans

In an earlier study, we exposed nine healthy volunteers to known concentrations of mercury (Hg) vapor in air (median 399; range 365-430 micrograms/m3) for 15 min during light physical exercise (50 W) (Sandborgh-Englund, G., et al., Toxicol. Appl. Pharmacol. 150, 146-153, 1998). Exhaled air, urine, and plasma samples were collected. In the present study, the experimental observations from eight of these volunteers were subjected to an analysis with the aid of the software NONMEM. A four-compartment model, including two depot compartments to account for retention in lungs and kidneys, respectively, gave the best fit to the data. The fraction of dose excreted from the central compartment directly into urine was found to be positively correlated with the preexposure excretion rate of Hg via urine. The median half time in the respiratory depot compartment was estimated to 1.81 days (range 1.60-1.92). The median half time in the excretion depot was estimated to 63.2 days (range 12.8-98.9). The model was tested by simulating two experiments found in the literature and agreed well with these older data sets. Further simulations indicated that the excretion of Hg via urine would not reach a plateau until several months postexposure for most subjects.