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In the Tegeris study (1987) rats were exposed to Cyclohexanone by inhalation at air concentrations fo 400 (males) and 1600 (females) for 6 hours. The animals lost weight and appeared sedated. The material was rapidly eliminated from the blood; concentrations of free cyclohexanone and cyclohexanol in the blood immediately after exposure were about 26.01 and 20.48 ug/mL, respectively, at the low dose and 121.76 and 140.43 ug/mL, respectively at the high dose. Only trace quantities of free cyclohexanol were seen at 24 hours. Total 72-hour urinary excretion volumes of free cyclohexanone and cyclohexanol were 16.16 and 14.55 ug, respectively, at the high dose. By 72 hours, the total excretion of conjugated cyclohexanol (primarily excreted during the first 24 hours) and another conjugated product, tentatively cyclohexanone, was 13,306.15 and 546.69 ug at the low dose and 72,446.56 and 890.94 ug at the high dose.

The metabolism and kinetics of cyclohexanone were studied in a group of volunteers (four men and four women) during and after 8-h exposures to 101, 207 and 406 mg/m3. After exposure to 207 mg/m3, the metabolic yields of urinary cyclohexanol, 1,2- and 1,4 -cyclohexanediol and their glucuronide conjugates were 1%, 39% and 18%, respectively. The elimination half-times (t½) of the 1,2- and 1,4-diols, respectively, were 16 h and 18 h. Consequently, after repeated exposure over five days, there was no cumulation of urinary cyclohexanol, whereas there was cumulative excretion of the diols. The permeation rate of cyclohexanone liquid through the skin was 37 - 69 mg/cm2 per hour, indicating that occupational exposure by this route is of minor importance (Mráz et al., 1994).

Conclusion:

In the rat, the major part is reduced to Cyclohexanol which is glucoronidated and excreted. In humans, the glucuronidation pathway is less important; the major part is ring-hydroxylated to 1.2- and 1.4 -diols which are excreted in glucuronidated and not glucuronidated form. Hence, the rat model has in the case of Cyclohexanone some limitations in terms of human relevance.