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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)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline animal experimental study, published in peer reviewed literature, minor restrictions in reporting but otherwise adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
On the pharmacokinetics of the ethanol metabolite acetate: Elimination from the blood and cerebrospinal fluid
Author:
Freundt KJ
Year:
1973
Bibliographic source:
Drug Res. 23: 949-951

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
The distribution and elimination kinetics of acetate were determined from concentrations in plasma and cerebral spinal fluid following single intravenous doses of sodium acetate.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium acetate
EC Number:
204-823-8
EC Name:
Sodium acetate
Cas Number:
127-09-3
Molecular formula:
C2H4O2.Na
IUPAC Name:
sodium acetate
Details on test material:
- Name of test material (as cited in study report): Sodium acetate, analytical grade (Merck, Darmstadt)
- No further details
Radiolabelling:
no

Test animals

Species:
dog
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight: 15-25 kg
- Diet: Altromin dry pellets ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- maintained under constant conditions

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
intravenous
Vehicle:
other: Ringer solution
Duration and frequency of treatment / exposure:
Single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
3-6mmol/kg
No. of animals per sex per dose / concentration:
Total of 5 (sex not reported)
Control animals:
no
Details on dosing and sampling:
The dose was injected into the left femoral vein at a rate of 48 mmol/min. Blood samples for the determination of acetate using an enzymic method were withdrawn from the right femoral vein.

Results and discussion

Preliminary studies:
Background concentrations of acetate in plasma and cerebral spinal fluid were determined in man, dog and rabbit. Concentrations (mean±SD) in plasma were 0.065±0.007 (n=9), 0.090±0.012 (n=15) and 0.088±0.022umol/mL (n=5) for man, dog and rabbit respectively; concentrations in cerebral spinal fluid were 0.091±0.007 and 0.089±0.013 in man and dog respectively.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
At plasma pH (7.4) only about 0.23% of the acetate was unionised and able to permeate across a lipid barrier. Over a 60 min period during which plasma concentrations of acetate were maintained at 22 umol/mL, the maximum concentration in cerebral spinal fluid (CSF) was approximately 20x lower than in plasma; the permeability (min-1) for distribution from plasma into CSF was 0.002±0.0009. The elimination half life from CSF was 14.6± 5.9 min.
Details on excretion:
Elimination half lives were 3.0±0.5, 4.0±0.3, 4.1±0.4 and 5.0±0.5 minutes at doses of 3, 4, 5 and 6 mM/kg, respectively.

Metabolite characterisation studies

Metabolites identified:
no

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Acetate distributed from plasma into cerebral spinal fluid and was rapidly eliminated. Elimination half lives were 3.0±0.5, 4.0±0.3, 4.1±0.4 and 5.0±0.5 minutes at doses of 3, 4, 5 and 6 mmol/kg, respectively