Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study provides incidental data on the metabolism of 1,1,1,3,3,3-hexafluoropropane-2-ol in human subjects.

Data source

Reference
Reference Type:
publication
Title:
Metabolism and Toxicity of the new anesthetic agents
Author:
Kharasch E D
Year:
1996
Bibliographic source:
Acta anaesthesiologica Belgica, Vol.47, No. 1, pp.7-14

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
The plasma and urinary metabolites of the anaesthetic Sevflurane were investigated in anaesthetised human subjects.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sevoflurane
Radiolabelling:
no

Test animals

Species:
human
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Data were obtained from anaesthetised humans

Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
unchanged (no vehicle)
Details on exposure:
Exposure of human subjects
Duration and frequency of treatment / exposure:
Single anaesthetic exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
No data
No. of animals per sex per dose:
No data
Control animals:
no
Positive control:
Not applicable
Details on study design:
The plasma and urinary metabolites of the anaesthetic Sevoflurane were investigated in anaesthetised human subjects.

Results and discussion

Preliminary studies:
No preliminary studies conducted.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not relevant for this study
Details on distribution in tissues:
Not investigated
Details on excretion:
1,1,1,3,3,3-hexafluoropropane-2-ol was excreted as the glucuronic acid conjugate

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
1,1,1,3,3,3-hexafluoropropane-2-ol was conjugated with glucuronic acid, with no evidence of defluorination.

Any other information on results incl. tables

1,1,1,3,3,3 -hexafluoropropane-2 -ol and its-glucuronide were identified as metabolites of Sevoflurane in exposed humans.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
1,1,1,3,3,3-hexafluoropropane-2-ol is rapidly conjugated to glucuronic acid and rapidly excreted in the urine of exposed humans. There was no evidence of defluorination and no bioaccumulation is predicted.
Executive summary:

1,1,1,3,3,3 -hexafluoropropane-2 -ol was identified as a metabolite of the anaesthetic Sevoflurane in human subjects. 1,1,1,3,3,3 -hexafluoropropane-2 -ol did not undergo further defluorination but was rapidly conjugated to glucuronic acid and rapidly excreted in the urine.