Studies in detoxication. 79. The metabolism of cyclo[14C]hexane and its derivatives

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Abstract
When cyclo[C14]hexane is administered to rabbits in doses of about 350 to 400 mg/kg, about 40% of the C14 appears in the expired air and about 50% in the urine in 2 days after dosing. With a dose of 0.3 mg/kg, only about 5% of the dose of C14 is found in the expired air and 90% in the urine. With the large dose, the C14-labeled compounds found in the expired air were CO2 (about 10% of the dose) and unchanged cyclohexane (about 30%), whereas with the small dose only labeled CO2 (5.5%) was found. The urinary metabolites of cyclohexane were cyclohexanol and trans-cyclohexane-1,2-diol, excreted as glucuronides. cyclo Hexyl-glucuronide was isolated and characterized. With the larger doses the cyclohexanol accounted for 35 to 50% and the diol for 3 to 8% of the dose, whereas the values for the small dose were cyclohexanol, 61%, and the diol, 16.7%. The ratio, cyclohexanol/cyclohexane-diol, was about the same for the large and small doses. cis-cycloHexane-l,2-diol, cyclohexanone, cyclohexane-1,2-dione, trans-cyclohexane-1,3- and -1,4-diol, cyclohexene oxide, cyclohex-2-en-l-ol, and adipic acid, succinic acid, maleic acid, malonic acid and oxalic acid, and phenol, do not appear to be urinary metabolites of cyclohexane. cycloHexanol is highly conjugated (65% of the dose) with glucuronic acid in the rabbit. The main metabolite is cyclohexyl glucuronide. About 6% of the dose is excreted as conjugated trans-cyclohexane-1,2-diol. cycloHexanone is reduced in rabbits and excreted mainly as cyclohexyl glucuronide. This glucuronide is also the main metabolite of cyclohex-1-en-l-ol, which was fed as its acetate. Both cis- and ([plus or minus])trans-cyclohexane-l,2-diol are excreted by rabbits, highly conjugated with glucuronic acid. The monoglucuronide of the trans-diol was isolated and characterized.