Barium di(acetate)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not specified

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:

Effect of 2,4-Dichlorophenoxyacetic acid on the in vivo metabolism of acetate in adult rats

Author:

Philleo, W. W. & Fang, S. C.

Year:

1967

Bibliographic source:

J. Agr. Food Chem. 15 (2): 256 - 260.

Materials and methods

Objective of study:

excretion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Male and female inbred Oregon State Wistar rats received radiolabelled sodium acetate (as sodium acetate-1-C14 or sodium acetate-2-C14 (females only)) as a single administration via gavage. Aqueous sodium acetate solution was prepared such that the specific activity was about 5 X 10E7 d.p.m./mL and had a concentration of 14.5 µmoles of acetate/mL. Rats were placed in a metabolic cage and excreta (expired CO2, urine, and faeces) were collected during a 24 hour period after administration, which were analysed for radioactivity.

GLP compliance:

not specified

Remarks:

not specified in the publication

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

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): sodium acetate-1-C14 and -2-C14 (obtained either from New England Nuclear Corp. or Volk Chemicals)

Specific details on test material used for the study:

not specified

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

other: inbred Oregon State Wistar strain

Details on species / strain selection:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 to 9 months old
- Weight at study initiation: males: 350 to 400g; females: 250 to 280 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Aqueous sodium acetate solution was prepared such that the specific activity was about 5 X 10E7 d.p.m. per mL and had a concentration of 14.5 µmoles of acetate per mL.

Females received sodium acetate-1-C14 and sodium acetate-2-C14, but males received only sodium acetate-1-C14.

Duration and frequency of treatment / exposure:

single administration

Doses / concentrations

Dose / conc.:

14.5 other: µmoles acetate/mL

No. of animals per sex per dose / concentration:

not specified

Control animals:

not specified

Positive control reference chemical:

not specified

Details on study design:

Light anesthetization with ethyl ether was used before the dosing of male rats. No anesthetization was used for the dosing of female rats.

Details on dosing and sampling:

TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: expired CO2, urine, and faeces

After the acetate-C14 was administered, the rat was placed in a Delmar metabolism cage and the CO2 was trapped by sodium hydroxide solution. The sodium hydroxide solution from the CO2 trap was changed periodically and was analyzed for radioactivity after conversion of CO2 to BaCO3. The BaCO3 was filtered onto a glass fiber disk, washed, and dried and the radioactivity counted with a thin mica window GM detector. All counts were corrected for self adsorption and background.

The urine samples were collected and clarified by centrifugation at low speed. Aliquots of 0.1 mL were analyzed for radioactivity in a Packard Tricarb Model 314S liquid scintillation spectrometer. The radioactivity in the faeces was obtained by extracting the faeces with a sufficient volume of 50 % ethanol. The solid materials were centrifuged out and an aliquot of the supernatant was analyzed for radioactivity. All countings were corrected for quenching by using C14-benzoic acid as an internal standard.

Statistics:

not specified

Results and discussion

Preliminary studies:

not specified

Main ADME results

Main ADME results 1

Type:

excretion

Results:

According to the authors, from 79 to 95 % of orally administered acetate-C14 was recovered in the form of 14CO2. Only a small amount of the radioactivity was found in the urine (1.2 to 2.8 %) and faeces (0.3 to 0.5 %).

Main ADME results 2

Results:

The radioactivity recovered from excreta during the first 24-hour period was considerably less from the males than from the females.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

not specified

Details on distribution in tissues:

not specified

Details on excretion:

- there are two separate rates for the elimination of 14CO2. The initial rate of elimination (1 to 8 hours postmedication) is very rapid and has a biological half-life of 4 to 6 hours, followed by a much slower rate of elimination (half life of about 25 hours).
- the maximum incorporation in the expired 14CO2 appears in the first hour.
- the rates of elimination for the methyl and carboxyl carbons are not exactly the same.
- the 14CO2 elimination rates of acetate-1-C14 in untreated adult rats are similar between the male and female animals, even though the accumulative recovery of expired 14CO2 was less in the male rat.
(please also refer to the field "Attached background material" below).

- from 79 to 95 % of orally administered acetate-C14 was recovered in the form of 14CO2. Only a small amount of the radioactivity was found in the urine (1.2 to 2.8 %) and faeces (0.3 to 0.5 %).
- radioactivity recovered from excreta during the first 24-hour period was considerably less from the males than from the females.
(please refer to table 1 in the field "Any other information on results incl. tables" below)

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

not specified

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

not specified

Any other information on results incl. tables

Table 1: Percentage of administered radioactivity recovered in 24 hours from excreta of adult rats

	Females – Acetate-1-C14	Females – Acetate-2-C14	Males – Acetate-1-C14
CO2	95.3	89.4	79.2
Urine	2.0	2.8	1.2
Faeces	0.5	0.5	0.3
Total	97.8	92.7	80.7

Applicant's summary and conclusion

Conclusions:

According to the authors, from 79 to 95 % of orally administered acetate-C14 was recovered in the form of 14CO2. Only a small amount of the radioactivity was found in the urine (1.2 to 2.8 %) and faeces (0.3 to 0.5 %).
The radioactivity recovered from excreta during the first 24-hour period was considerably less from the males than from the females.