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Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
1,2- and 1,4-cyclohexanediol: major urinary metabolites and biomarkers of exposure to cyclohexane, cyclohexanone and cyclohexanol in humans
Author:
Mráz J, Gálová E, Nohová H, Vítková D
Year:
1998
Bibliographic source:
International Archives of Occupational and Environmental Health 71: 560-565

Materials and methods

Type of study / information:
Basic toxicokinetic and metabolism in humans
Endpoint addressed:
basic toxicokinetics
Principles of method if other than guideline:
The metabolism and toxicokinetics of cyclohexanol were studied over 72 hours in a group of 8 human volunteers exposed by inhalation to cyclohexanol vapours for a period of 8 hours.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Cyclohexanol
EC Number:
203-630-6
EC Name:
Cyclohexanol
Cas Number:
108-93-0
Molecular formula:
C6H12O
IUPAC Name:
cyclohexanol
Test material form:
not specified
Details on test material:
Supplier: Fluka, Buchs, Switzerland.

Method

Ethical approval:
other: Conducted with informed consent according to the recommendations of the Declaration of Helsinki and were approved by the Scientific Committee of the Czech Ministry of Health.
Details on study design:
Groups of two to four subjects were exposed to vapours of cyclohexanol in closed chambers of 64 m3. The vapours were generated from the appropriate amounts of liquid cyclohexanol. Vapour supply was controlled by feedback from a gas chromatograph equipped with an automatic gas sampler analysing the cyclohexanol concentration at 5 minute intervals. The coefficient of variation of measured concentration ranged from 3 to 8%. The mean temperature and the relative humidity during the exposure periods were 26 °C and 60%, respectively. Subjects were exposed for a duration of 8 hours from 8.00 a.m. to 4.00 p.m. The subjects were at rest during the exposure experiments. They left the exposure chamber at 2-hour intervals for 2 to 3 minutes to void urine.
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE MEASUREMENT:
- measurement of concentrations by gas chromatograph and measurement of urinary concentrations of cyclohexanol, 1,2- and 1-4-cyclohexane-diol

EXPOSURE LEVELS:
- 236 mg/m3 (mean measured concentration)

EXPOSURE PERIOD:
- 8 hours

POSTEXPOSURE PERIOD:
- 72 hours

Results and discussion

Results:
Inhalation of cyclohexanol:
- Absorption A dose of 8.46 +/- 1.85 mmol of cyclohexanol was absorbed via the respiratory tract (Retention in respiratory tract: 64.2 +/- 1.9%).
Metabolism/Excretion
- Peak excretion of cyclohexanol was reached in all subjects at the end of the exposure period after which it decayed rapidly. The excretion curves for 1,2- and 1,4-cyclohexane-diol reached their peaks a few hours post exposure. Half-life 1st: cyclohexanol excretion: 1.5 h Half-life 1st: for 1,2 cyclohexane-diol excretion: 14.3 +/- 1.2 h Half-life 1st: for 1,4 cyclohexane-diol excretion: 18 +/- 2.5 h Inhalation exposure to cyclohexanol resulted in the urinary excretion of cyclohexanol and 1,2- and 1,4-cyclohexane-diol with yields of 1.1 +/- 0.3%, 19.1 +/- 3.8% and 8.4 +/- 1.4%, respectively, of the absorbed dose. Only the 1,2-cyclohexane-diol is eliminated in conjugation with glucoronic acid. Cyclohexanone was not detected in urine after exposure to cyclohexanol.

Any other information on results incl. tables

Inhalation of CH-ol:

Absorption

The dose absorbed was calculated as a product of the concentration in the air, the pulmonary ventilation during 8 h, and the retention in the respiratory tract. A dose of 8.46 +/- 1.85 mmol of cyclohexanol was absorbed via the respiratory tract.

Measured parameter

Minute respiratory volume: 11.7 +/- 2.5 L/min

Retention in respiratory tract: 64.2 +/- 1.9%

Metabolism/Excretion

The values for the half-lives of elimination were calculated by least-squares linear regression analysis of log-plots of the excretion curves of cyclohexane-diols in the interval from 14 -72 h after the start of 8-h periods of inhalation exposure.

No sex specific difference found with regard to the elimination half-lives of the metabolites.

Applicant's summary and conclusion

Conclusions:
Eight human subjects were exposed by inhalation to cyclohexanol vapours at a concentration of 236 mg/m3 over a period of 8 hours. Urine samples were collected during the exposure period and over a period of 72 hours post-exposure. Cyclohexanol and its metabolites 1,2-cyclohexane-diol and 1,4-cyclohexane-diol were excreted in urine at a proportion of the absorbed dose corresponding to 1.1%, 19.1% and 8.4%, respectively.