Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
tests for metabolism and pharmacokinetics propably according or equivalent to OECD 417
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
HFA22
IUPAC Name:
HFA22
Constituent 2
Chemical structure
Reference substance name:
Chlorodifluoromethane
EC Number:
200-871-9
EC Name:
Chlorodifluoromethane
Cas Number:
75-45-6
Molecular formula:
CHClF2
IUPAC Name:
chlorodifluoromethane
Details on test material:
no data
Radiolabelling:
not specified

Test animals

Species:
human
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
groups of 3 male humans, no further information

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
not specified
Details on exposure:
exposure to vapor concentrations in an inhalation chamber
Duration and frequency of treatment / exposure:
4 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
92 or 518 ppm
No. of animals per sex per dose / concentration:
no data
Control animals:
not specified
Positive control reference chemical:
no data
Details on study design:
no data
Details on dosing and sampling:
Blood and expired air samples were
taken during exposure and for up to 26 hours after exposure. Urine samples
were taken for up to 22 hours after exposure.
Statistics:
no data

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The compound was absorbed
very quickly, reaching plateaus of 0.25 and 1.36 ug/ml after approximately
4 and 3 hours of exposure for the low- and high-dose levels, respectively.
End-tidal breath concentrations of the test compound during exposure were
similar to the exposure concentrations, indicating that only a small
proportion of the available dose was absorbed.
Details on distribution in tissues:
Elimination of the compound
from blood was triphasic, with estimated half-lives of 0.005, 0.20, and 2.7
hours. The first phase probably corresponded to elimination from blood and
rapidly perfused tissues, whereas the second and third phases of
elimination probably corresponded to elimination from slowly perfused
tissues and fat, respectively.
Details on excretion:
The parent compound was detected in urine
samples from all subjects; very little fluoride ion was detected in urine
samples.

Metabolite characterisation studies

Metabolites identified:
not specified
Details on metabolites:
test compound was probably not metabolized to
a significant extent

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: expert judgement
Executive summary:

In tests for metabolism and pharmacokinetics chlorodifluoromethane) was evaluated in groups of 3 male humans exposed via inhalation to vapor concentrations of 92 or 518 ppm for 4 hours in an inhalation chamber. Blood and expired air samples were taken during exposure and for up to 26 hours after exposure. Urine samples were taken for up to 22 hours after exposure. The compound was absorbed very quickly, reaching plateaus of 0.25 and 1.36 ug/ml after approximately 4 and 3 hours of exposure for the low- and high-dose levels, respectively. End-tidal breath concentrations of the test compound during exposure were similar to the exposure concentrations, indicating that only a small proportion of the available dose was absorbed. Elimination of the compound from blood was triphasic, with estimated half-lives of 0.005, 0.20, and 2.7 hours. The first phase probably corresponded to elimination from blood and rapidly perfused tissues, whereas the second and third phases of elimination probably corresponded to elimination from slowly perfused tissues and fat, respectively. The parent compound was detected in urine samples from all subjects; very little fluoride ion was detected in urine samples, indicating that the test compound was probably not metabolized to a significant extent.