1,2- and 1,4-Cyclohexanediol: major urinary metabolites and biomarkers of exposure to cyclohexane, cyclohexanone, and cyclohexanol in humans.
The metabolism and toxicokinetics of cyclohexane (CH) and cyclohexanol (CH-ol), important solvents and chemical intermediates, were studied in volunteers after 8-h periods of inhalation exposure at concentrations of 1010 and 236 mg m(-3), respectively (occupational exposure limits: CH, 1050 mg m(-3); CH-ol, 200 mg m(-3)). Of the dose of absorbed parent compounds, the yields of urinary CH-ol and 1,2- and 1,4-cyclohexanediol (CH-diol) were 0.5%, 23.4%, and 11.3%, respectively, after exposure to CH and 1.1%, 19.1%, and 8.4%, respectively, after exposure to CH-ol as determined by a gas chromatography method involving hydrolysis of glucuronide conjugates. The metabolic patterns of CH and CH-ol were very similar to that of cyclohexanone (CH-one) studied in the laboratory previously. For all three compounds, peak excretion of CH-ol occurred at the end of the exposure period, after which it decayed rapidly. Excretion curves of 1,2- and 1,4-CH-diol reached maximal values within 0-6 h postexposure, with subsequent elimination half-lives being 14-18 h. The rate-limiting step in the elimination of CH compounds from the organism is renal clearance of CH-diols. Determination of CH-diols in end-of-shift urine samples is recommended as a useful new method of biomonitoring of CH, CH-ol, and CH-one at the workplace. However, due to accumulation of CH-diols in the body during repeated exposure, quantitative relationships between the exposure and the level of CH-diols have to be adjusted according to the day of sampling during the working week.
Mráz
J
J
National Institute of Public Health, Prague, Czech Republic.
Gálová
E
E
Nohová
H
H
Vitková
D
D
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002849:Chromatography, Gas; D003510:Cyclohexanes / Q000493:pharmacokinetics*; D003511:Cyclohexanols / Q000493:pharmacokinetics* / Q000652:urine*; D003512:Cyclohexanones / Q000493:pharmacokinetics*; D004784:Environmental Monitoring / Q000379:methods; D005260:Female; D006207:Half-Life; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D003510:Cyclohexanes; D003511:Cyclohexanols; D003512:Cyclohexanones; C064620:1,4-cyclohexanediol; C036468:cyclohexanone; C064619:1,2-cyclohexanediol