Ammonium acetate

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No specific test guideline was reported; however, a scientifically defensible approach was used to conduct the study.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1969

Report date:

1968

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

not applicable

Principles of method if other than guideline:

The toxicity of ammonium acetate was studied in humans after an intravenous infusion. In the first experiment, 80-160 meq of ammonium acetate (1.12 and 2.24 g of N, respectively), dissolved in 1 liter of a solution containing 5% of glucose and 5% of fructose (Invertos), were infused intravenously within 3 hours. In the second experiment, 200 meq of ammonium acetate (2.8 g of N) were infused during about 4 hours twice in two subjects, together with 8.8 and 17.6 g of L-arginine, supposed to protect against the toxic symptoms.
The plasma ammonia concentration was determined before the start of the infusion, at the end of the infusion, and thirty minutes later. The pH of arterial blood wa measured before and immediately after the infusion.

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

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 9 adult humans
- Sex: 5 women and 4 men
- Other: Experiments were carried out on reliable healthy human volunteers or on not bedridden patients treated for uncomplicated and nearly healed bone fractures.
These subjects had not been on any special diet prior to the experiment, which was carried through in the morning when the subjects were in the postabsorptive state.

Ethical approval:

not specified

Route of exposure:

other: intravenous

Reason of exposure:

intentional

Exposure assessment:

not specified

Details on exposure:

Experiment I:
80-160 meq of ammonium acetate (1.12 and 2.24 g of N, respectively), dissolved in 1 liter of a solution containing 5% of glucose and 5% of fructose (Invertos), were infused intravenously within 3 hours.

Experiment II:
200 meq of ammonium acetate (2.8 g of N) were infused during about 4 hours twice in two subjects, together with 8.8 and 17.6 g of L-arginine, supposed to protect against the toxic symptoms.

Examinations:

- The plasma ammonia concentration was determined before the start of the infusion, at the end of the infusion, and thirty minutes later.
- The pH of arterial blood wa measured before and immediately after the infusion.

Results and discussion

Clinical signs:

Experiment I:
One subject felt a little unconfortable during the infusion, with a slight feeling of nausea and tennitus and inappreciable vomiting. The symptoms disappeared immediately after the infusion was discontinued.
The slight symptoms of discomfort were practically independent of the total amount of ammonium salt infused, since they were even less frequent after the higher ammonia dose.

Experiment II:
It was observed that the susceptibility to ammonia could be considerably decreased by infusing the ammonium salts together with amino acids. When the acetate was given with 8.8 g of L-arginine, both subjects felt nauseated, but no with 17.6 g of this amino acid.

Results of examinations:

Experiment I: Results of the two experiments in which 160 meq of ammonium acetate:
- One subject reached a blood concentration of 2.3 µg of ammonia N per milliliter, and the other a concentration of 3.1 µg/mL.
- Neither blood pH nor P(CO2) was appreciably changed.

Any other information on results incl. tables

In the first experiment, one subject felt a little unconfortable during the infusion, with a slight feeling of nausea and tennitus and inappreciable vomiting. The symptoms disappeared immediately after the infusion was discontinued. The slight symptoms of discomfort were practically independent of the total amount of ammonium salt infused, since they were even less frequent after the higher ammonia dose.

It was observed that the susceptibility to ammonia could be considerably decreased by infusing the ammonium salts together with amino acids. When the acetate was given with 8.8 g of L-arginine, both subjects felt nauseated, but no with 17.6 g of this amino acid.

In the two experiments in which 160 meq of ammonium acetate, one subject reached a blood concentration of 2.3 µg of ammonia N per milliliter, and the other a concentration of 3.1 µg/mL. Neither blood pH nor P(CO2) was appreciably changed.

Applicant's summary and conclusion

Conclusions:

In the first experiment, one subject felt a little unconfortable during the infusion, with a slight feeling of nausea and tennitus and inappreciable vomiting. The symptoms disappeared immediately after the infusion was discontinued. The slight symptoms of discomfort were practically independent of the total amount of ammonium salt infused, since they were even less frequent after the higher ammonia dose.
It was observed that the susceptibility to ammonia could be considerably decreased by infusing the ammonium salts together with amino acids. When the acetate was given with 8.8 g of L-arginine, both subjects felt nauseated, but no with 17.6 g of this amino acid.
In the two experiments in which 160 meq of ammonium acetate, one subject reached a blood concentration of 2.3 µg of ammonia N per milliliter, and the other a concentration of 3.1 µg/mL. Neither blood pH nor P(CO2) was appreciably changed.

Executive summary:

The toxicity of ammonium acetate was studied in humans after an intravenous infusion. In the first experiment, 80-160 meq of ammonium acetate (1.12 and 2.24 g of N, respectively), dissolved in 1 liter of a solution containing 5% of glucose and 5% of fructose (Invertos), were infused intravenously within 3 hours. In the second experiment, 200 meq of ammonium acetate (2.8 g of N) were infused during about 4 hours twice in two subjects, together with 8.8 and 17.6 g of L-arginine, supposed to protect against the toxic symptoms.

The plasma ammonia concentration was determined before the start of the infusion, at the end of the infusion, and thirty minutes later. The pH of arterial blood wa measured before and immediately after the infusion.

In the first experiment, one subject felt a little unconfortable during the infusion, with a slight feeling of nausea and tennitus and inappreciable vomiting. The symptoms disappeared immediately after the infusion was discontinued. The slight symptoms of discomfort were practically independent of the total amount of ammonium salt infused, since they were even less frequent after the higher ammonia dose.

It was observed that the susceptibility to ammonia could be considerably decreased by infusing the ammonium salts together with amino acids. When the acetate was given with 8.8 g of L-arginine, both subjects felt nauseated, but no with 17.6 g of this amino acid.

In the two experiments in which 160 meq of ammonium acetate, one subject reached a blood concentration of 2.3 µg of ammonia N per milliliter, and the other a concentration of 3.1 µg/mL. Neither blood pH nor P(CO2) was appreciably changed.