Ammonium acetate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Test method was not according to any guideline. No GLP.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1969

Report date:

1968

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Principles of method if other than guideline:

The uptake and urea formation of ammonia in the liver were studied in healthy volunteers by means of hepatic vein catheterization after an oral administration of Ammonium acetate.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium acetate

EC Number:

211-162-9

EC Name:

Ammonium acetate

Cas Number:

631-61-8

Molecular formula:

C2H4O2.H3N

IUPAC Name:

ammonium acetate

Details on test material:

- Name of test material (as cited in study report): Ammonium acetate

Radiolabelling:

yes

Test animals

Species:

human

Strain:

other: not applicable

Sex:

not specified

Details on test animals or test system and environmental conditions:

Test subjects had been on the nitrogen-poor diet (2.7 g of N) for 4 days prior to the experiment. They were in the post absorptive state.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Duration and frequency of treatment / exposure:

One single administration

Doses / concentrations

Remarks:

Doses / Concentrations:
10.5-11.1 mg of ammonia nitrogen (0.80 meq) per minute.

No. of animals per sex per dose / concentration:

Two subjects (no data on sex distribution).

Control animals:

no

Details on dosing and sampling:

- Two or three basal periods were studied before starting the infusion.
- The estimated splanchnic blood flow (ESBF) was calculated by means of Cardio-Green throughout the experiments.
- Blood samples for determination of urea and ammonia were taken from a peripheral artery and from the hepatic vein at the beginning and at the end of periods of about 5-20 min, for about 2 hr.
- The production (output) and the consumption (uptake), respectively, of the liver were calculated by multiplying concentration differences between hepatic vein blood and peripheral arterial blood by ESBF.
- Heparinized blood samples for ammonia determinations were always examined immediately after withdrawing and rapid centrifuging.
- Ammonia, alfa-amino nitrogen, total protein, and urea nitrogen concentrations were determined in the plasma, as were the 24-hr excretion of ammonia, alfa-amino nitrogen, urea nitrogen, creatinine, and total nitrogen in the urine.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

N absorption after oral loading of NH4+ is complete.

Details on distribution in tissues:

Human oral exposure data for NH4+ clearly indicate that it readily enters the portal circulation and is delivered to the liver.

Details on excretion:

Urea, the main metabolite, was excreted in the urine. Output of urea from the liver corresponded to the amount of NH4+ ingested. Excretion data for humans orally exposed to ammonia have been quantified with respect to excretion of isotope from 15N-labeled ammonium salts, thus providing an indication of the turnover rate of the compound within the body and excretion route of its metabolites.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

In nitrogen-deficient persons, NH4+ (as ammonium acetate) administered orally was absorbed and carried directly to the liver where most of it was converted to urea.

Any other information on results incl. tables

Ammonium salt administered orally to humans led to a corresponding increase in blood urea concentration transported out of the liver, leading the authors to conclude that orally ingested ammonium salt is quickly and almost completely converted in the liver and eliminated from the body as urinary urea.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: other: orally ingested ammonium salt is quickly and almost completely converted in the liver and eliminated from the body as urinary urea.
Ammonium salt administered orally to humans led to a corresponding increase in blood urea concentration transported out of the liver, leading the authors to conclude that orally ingested ammonium salt is quickly and almost completely converted in the liver and eliminated from the body as urinary urea.

Executive summary:

The uptake and urea formation of ammonia in the liver were studied in healthy volunteers by means of hepatic vein catheterization after an oral administration of Ammonium acetate.

N absorption after oral loading of NH4+ is complete.

Human oral exposure data for NH4+ clearly indicate that it readily enters the portal circulation and is delivered to the liver.

Urea, the main metabolite, was excreted in the urine. Output of urea from the liver corresponded to the amount of NH4+ ingested. Excretion data for humans orally exposed to ammonia have been quantified with respect to excretion of isotope from 15N-labeled ammonium salts, thus providing an indication of the turnover rate of the compound within the body and excretion route of its metabolites.

Ammonium salt administered orally to humans led to a corresponding increase in blood urea concentration transported out of the liver, leading the authors to conclude that orally ingested ammonium salt is quickly and almost completely converted in the liver and eliminated from the body as urinary urea.