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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Pharmacokinetics, carciovascular and metabolic actions of cyclohexylamine in man
Author:
Eichelbaum M, Hengstmann JH, Rost HD, Brecht T, Dengler HJ
Year:
1974
Bibliographic source:
Arch Toxicol 31, 243-263

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
Cyclohexylamine was administered orally in doses of 2.5, 5, amd 10 mg/kg bw to 11 healthy volunteers to determine absorption, plasma half lives, excretion, and biochemical effects
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Cyclohexylamine
EC Number:
203-629-0
EC Name:
Cyclohexylamine
Cas Number:
108-91-8
Molecular formula:
C6H13N
IUPAC Name:
cyclohexanamine
Details on test material:
cyclohexylamine purissimum adjusted with hydrochloric acid to a pH of about 7 (no further data)
Radiolabelling:
no

Test animals

Species:
human
Strain:
other: medical or laboratory staff members familiar with Cyclamate/cyclohexylamine problem
Sex:
male

Administration / exposure

Route of administration:
other: oral (total dose at once)
Vehicle:
water
Duration and frequency of treatment / exposure:
once
Doses / concentrations
Remarks:
Doses / Concentrations:
2.5, 5, 10 mg/kg bw
No. of animals per sex per dose / concentration:
total number : 11 male healthy volunteers; they fasted over night and did not take any food or fluid during the first 4 hours of the experiment.
They were lying in a quiet room 30 min before and 4 hours after ingestion of the testsubstance
Control animals:
not specified

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Almost complete enteral absorption
Type:
excretion
Results:
86 -95 % of the administered doses were excreted in the urine during 48 hours as unchanged compound

Toxicokinetic / pharmacokinetic studies

Details on absorption:
levels of cyclohexylamine could be observed already 15 min after the administration.
Peak levels were obtained 90-120 min after dosing; thereafter the falll in plasma cyclohexylamine was shown to be linear when plotted on a semilogarithmic scale
Details on distribution in tissues:
no data
Details on excretion:
no further data
Toxicokinetic parameters
Toxicokinetic parameters:
other: half life in plasma ranged from 3.5 -4.8 hours:clear dose dependency

Metabolite characterisation studies

Metabolites identified:
no

Any other information on results incl. tables

Cyclohexylamine caused a dose dependent rise in arterial blood pressure . A close correlation between plasma level of CHA and increase in mean arterial blood pressure could be established. A significant increase in fatty acids and cumulative urinary excretion of catecholamine was observed only after the administration of 10 mg/kg bw.

Applicant's summary and conclusion