Cyclohexylamine

Endpoint summary

Description of key information

Orally administered cyclohexylamine is rapidly and almost completely absorbed in both man and animals with peak blood or plasma level occurred between 1 and 2 hours and the half-life ranged from 3 to 5 hours.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Orally administered cyclohexylamine is rapidly and almost completely absorbed in both man and animals (dog, rat, guinea pig, rabbit). After administration of oral doses of 2.5, 5 and 10 mg/kg bw to volunteers, peak blood or plasma level occurred between 1 and 2 hours and the half-life ranged from 3 to 5 hours. In rats and dogs, the peak cyclohexylamine levels in blood or plasma were achieved within the first hour, and the half-lifes were about 1 to 2 hours and 3 hours, respectively (Bopp et al., 1986, Eichelbaum et al., 1974, Renwick and Williams 1972).

In rats the highest concentrations were observed in lungs, spleen, liver, adrenal glands, heart, gastrointestinal tract and kidneys. Only 8% of the cyclohexylamine was bound to plasma protein, whereas binding to human serum albumin was determined at 33%. The apparent distribution volume in humans of 2.1 to 2.9 l/kg agreed well with the values in rats, 2.7 l/kg (Bopp et al., 1986, Eichelbaum et al., 1974).

Cyclohexylamine diffuses across the placental barrier and thus might reach the fetus, as studies in pregnant rhesus monkeys have demonstrated (Bopp et al., 1986, Pitkin et al. 1969).

In humans and in experimental animals approximately 90% or more of the administered dose is eliminated in the urine. In humans, the renal clearance of cyclohexylamine exceeded that of creatinine, as indicated by both by elimination via tubular secretion as well as glomerular filtration. Since the renal clearance decreased when the dose is increased (from 2.5 to 10 mg/kg bw) a low-level of saturability is assumed in the secretion process. (Bopp et al., 1986, Eichelbaum et al., 1974).

Cyclohexylamine is absorbed and eliminated more rapidly by mice than by rats. In rats, plasma clearance in the steady state emounted to approximately half by comparison with that of mice. Contrary to the data found in mice, the concentration of cyclohexylamine in the testes of rats did not correlate with the dose in a linear fashion. The kinetics is therefore devisive in producing the difference in the occurance of testicular effects in rats versus mice (Roberts and Renwick 1989).

Following oral application of 25-50 mg/per person or 50-500 mg/kg in animals 1-2% of the administered dose was metabolized in humans, compared to approx. 10% in female guinea pigs and approx. 30% in rabbits. The only metabolite found was transcyclohexane-1,2-diol. In the rat ring hydroxylation occurred, resulting in isomers of 3- or 4-aminocyclohexanol. In guinea pigs and rabbits deamination (via CYP 450) and ring hydroxylation was reported. Both cyclohexanone and cyclohexanol were identified in dogs (Bopp et al., 1986, Eichelbaum et al., 1974, Kurebayashi et al., 1990, Roberts and Renwick 1989).