Acetic acid

Basic toxicokinetics

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

Test material information

Constituent 1

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 Blood samples for the determination of acetate using an enzymic method were withdrawn from the right femoral vein.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