Kinetics of methyl ethyl ketone in man: absorption, distribution and elimination in inhalation exposure

Abstract

The kinetics of inhaled methyl ethyl ketone (MEK) in human volunteers was studied in an exposure chamber. Relative pulmonary uptake was about 53% throughout a 4-h exposure period at 200 ppm. Blood MEK concentration rose steadily until the end of exposure. Repeated bicycle exercise increased the overall blood MEK level markedly in comparison to sedentary activity, with transient peaks in association with cycling; thus blood MEK concentration depended both on the rate of uptake and the amount taken up. Only 3% of the absorbed dose was excreted unchanged by exhalation. A well-known metabolite of MEK, 2,3-butanediol, was detected in the urine with maximum rates of excretion at about 6 to 12 h from the beginning of exposure. About 2% of the MEK dose taken up by the lungs was excreted in the urine as 2,3-butanediol. The main part of inhaled MEK is supposedly metabolized in the intermediary metabolism. Elimination of MEK in blood appeared to exhibit two phases: the initial alpha-phase (T1/2 = 30 min; kel alpha = 0.023) over the first post-exposure hour, followed by the terminal beta-phase (T1/2 = 81 min; kel beta = 0.009).