Uptake, metabolism and elimination of cyclohexanone in humans.

The metabolism and toxicokinetics of cyclohexanone (CH-one), an important solvent and chemical intermediate, have been studied in volunteers during and after 8-h exposures to CH-one vapour at a concentration of 101, 207 and 406 mg.m-3. The pulmonary ventilation in these experiments was typically 11 l.min-1 and retention in the respiratory tract was 58%. After exposure to CH-one, 207 mg.m-3, the metabolic yields of cyclohexanol (CH-ol), 1,2- and 1,4-cyclohexanediol (CH-diol) as determined in urine by a gas chromatographic method involving hydrolysis of glucuronide conjugate were 1.0% +/- 0.3%, 39% +/- 5% and 18% +/- 2% (n = 8), respectively. Peak excretion of CH-ol was achieved at the end of the exposure period, after which it decayed rapidly. Elimination of 1,2- and 1,4-CH-diol reached maximum values a few hours following exposure, with subsequent elimination half-times of 16 +/- 2 and 18 +/- 4 h, respectively. Repeated exposure to CH-one vapour (around 200 mg.m-3) for five consecutive days (8 h/day) resulted in cumulative excretion of CH-diols. The permeation rate of CH-one liquid through the skin was 0.037-0.069 mg.cm-2.h-1 (n = 3), indicating that the contribution of percutaneous absorption to total CH-one occupational intake is of minor importance. CH-diols are recommended as biomarkers of exposure to CH-one.