Abstract |
The pharmacokinetics of cyclohexane was studied in adult male Fischer 344 rats administered 10 mg/kg 14C-cyclohexane by intravenous injection. At 72 hours, the concentration of 14C in adipose averaged 16 times that in blood. Cyclohexane accounted for 79 to 84% of the radiolabel in adipose, but only 1 to 18% of it in muscle, liver and skin. Small amounts of cyclohexanone and cyclohexanol accounted for the remainder of the C14 present. Most of the radiolabel was excreted in the breath (54% in the 1st hour; 80% in 24 hours, and 83% in 72 hours), 14% in urine, and trace amounts in feces. After oral administration of 2000, 1000, 200, or 100 mg/kg of 14C-cyclohexanone to rats , 78, 76, 62, and 63% C14, respectively, was eliminated in the breath, and 12, 15, 29, and 29% in urine. Again, trace amounts of C14 were eliminated in feces. Three major urinary metabolites, apparently conjugated forms that constituted approximately 1 to 15% of the radioactive dose, were observed but not characterized. Plasma content of 14C was fairly constant (approximately 9.0 to 14.1 ug-eq/g of plasma) from 2 to 12 hours post treatment, but decreased to about 20% of this by 24 hours. Cyclohexane, cyclohexanone, and cyclohexanol accounted for most of the plasma 14C at 6 to 24 hourspost-dosing. At least 5 other unidentified metabolites were found (at 14C-concentrations ranging from approximately 0.14 to 0.74 ug-eq/g at 24 hours). Distribution followed the same pattern after oral dosing as after intravenous administration. The half-lives of total 14C in plasma and tissues, including adipose, were generally about 10 to 15 hours. |