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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.

A simple and sensitive method for determining urinary cyclohexanol, the main metabolite of cyclohexanone, by hydrolysis and gas chromatography (GC) with a flame ionization detector was developed. A 2-mL urine sample was hydrolyzed with 0.4 mL of concentrated HCl and followed by extracting twice with diethylether. Two microL of the filtrate was injected into the GC with a methyl silicone column. The detection limit is estimated to be 0.4 mg/L. The coefficient of variation for the procedure is 8% and 10% for the range of concentration 5 and 50 mg/L, respectively. The within-run variation was 5.4% and between-day variation was 9.67%. The method was verified with urine samples collected from workers exposed to cyclohexanone. An excellent correlation (r = 0.88) was observed between environmental cyclohexanone exposure and cyclohexanol in urine. The procedure is relatively simple and reproducible and it can be applied for occupational health measurement of cyclohexanone exposure.

Using gas chromatography-mass spectrometry, we investigated the urinary excretion of organic acids of 278 newborn babies in a special care unit to obtain reference data and monitor metabolism. In 101 of 584 urine samples analyzed, we found isomers of cyclohexanediol. trans-1,2-Cyclohexanediol was always most abundant, with small amounts of 1,3- and 1,4-cyclohexanediol and, sometimes, traces of cis-1,2-cyclohexanediol. Glucuronide conjugates were not detected. The probable source was the solvent cyclohexanone, which was found as a contaminant of intravenous dextrose and the parenteral feeding solution, and was also leached into the infusion fluids from the administration set. We recovered 0.89 mg (range 0.74-0.98 mg, n = 5) of cyclohexanone from 150 mL of dextrose pumped through the infusion apparatus over 24 h, the normal rate for a 1-kg premature baby. Although this is well below toxic doses reported for mature animals, more data are needed for the newborn, particularly preterm infants who have a decreased capacity for glucuronide conjugation.

The cataractogenic potential of cyclohexanone administered intravenously (0.5 and 5.0 mg/kg) and percutaneously (0.5 ml) was assessed in guinea pigs and rabbits. The negative control article was 0.9% sodium chloride. Positive control articles for guinea pigs were iv galactose and percutaneous dimethyl sulfoxide (DMSO), and for rabbits, iv poly(I) X poly(C) and percutaneous DMSO. An untreated group of guinea pigs was used as a sham control. Animals were treated three times a week for 3 consecutive weeks. Ophthalmic examinations performed monthly for 6 months for treated animals and 7 months for untreated animals revealed the presence of anterior subcapsular vacuoles in guinea pigs in all groups. These lesions consisted of swollen lens fibers that progressed to fiber disruption and protein liquefaction. There was no statistical difference in the incidence and severity of the lesions among treatment groups. No lenticular alterations were noted in any of the rabbits treated with cyclohexanone or any other chemical. It was concluded that these alterations are, apparently, an inherent characteristic of the guinea pig, making that animal an unsuitable model for the assessment of cataractogenic potential of xenobiotics.