Ammonium bromide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1960

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: study was performed prior to the implementation of official testing guidelines

Data source

Reference

Reference Type:

publication

Title:

The Biological Half-life of Bromide ions in Human Blood

Author:

Söremark, R.

Year:

1960

Bibliographic source:

Acta physiol. Scand., 50, 119-123

Materials and methods

Objective of study:

other: biological half-life

Test guideline

Qualifier:

no guideline available

Deviations:

not applicable

Remarks:

study was performed prior to the implementation of official testing guidelines

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium bromide

EC Number:

235-183-8

EC Name:

Ammonium bromide

Cas Number:

12124-97-9

Molecular formula:

BrH4N

IUPAC Name:

Bromide activated chloramine (BAC) generated from ammonium bromide and sodium hypochlorite

Details on test material:

- Name of test material (as cited in study report): Ammonium bromide
- Radiolabelling: 82Br in form of NH4Br
- No further details given on test material within the publication.

Radiolabelling:

yes

Remarks:

82Br in form of NH4Br

Test animals

Species:

human

Strain:

other: not applicable

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not applicable
- Age at study initiation: between 19 and 23 years
- Weight at study initiation: women were within a weight range of 55-64 kg and men of 62-78 kg

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

10 µCi of 82Br in the form of NH4Br was dissolved in 25 ml water; this corresponds to less than 0.05 mg ammonium bromide (0.041 mg bromide).

Duration and frequency of treatment / exposure:

single oral administration

Doses / concentrations

Remarks:

Doses / Concentrations:
10 µCi of 82Br in the form of NH4Br was dissolved in 25 ml water; this corresponds to less than 0.05 mg ammonium bromide (0.041 mg bromide)

No. of animals per sex per dose / concentration:

Four women and six men participated in the investigation

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled : blood
- Time and frequency of sampling:Twice daily for a period of 4 days

Statistics:

Not applicable

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No significant difference in the concentration, related to the time of the day at which the measurement was made, could be observed. The highest concentration was reached within 1-4 hours after the radioactive solution had been taken.

Details on distribution in tissues:

The individual concentration of radiobromide in blood cells was determined by measuring the 82Br concentration of the whole blood sample and of the sample of serum. The amount of 82Br ions transferred to the cells was calculated with the use of the haematocrit values. In the human subjects studied it was found that of the whole amount of 82Br in the blood, between 26 and 34% was transferred into the cells. The ratio red blood cells to serum of bromide ions was about 0.45.
In no case were significant amounts of 82Br observed in fat or proteins

Details on excretion:

The effective half-life of 82Br ions in human blood was found to be 32 hours and the biological half-life about 12 hours.

Toxicokinetic parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

other: effective half-life: 32 hours

Toxicokinetic parameters 2

Toxicokinetic parameters:

other: biological half-life: 12 hours

Any other information on results incl. tables

The concentration of⁸²Br in the blood at different times after the oral administration of NH₄Br solution revealed that the radioactivity varied between 200 and 400 counts/min/ml blood at five hours after⁸²Br was given.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results , since in no case significant amounts of 82Br were observed in fat or proteins
From the investigation it can be concluded that the effective half-life of 82Br ions in human blood is 32 hours and the biological half-life about 12 hours. Bromide was preferentially distributed in the serum with a ratio red blood cells to serum of bromide ions of about 0.45.

Executive summary:

Materials and Methods

The biological half-life of bromide was studied in 10 human subjects. Radioactive isotope of bromide was given orally in form of ammonium bromide in water solution. Venous blood samples were drawn twice a day. In addition to the biological half-life, the bromide ratio red blood cells to serum was determined after measuring the individual haematocrit value in order to determine the amount of bromide transferred to blood cells.

Results and Discussion

Bromide belongs to those elements which are present in very small amounts in the body. An average value for human blood of 3.7 mg/L, had been found, however, with great individual variations. A ratio of Br/Cl of roughly 1:1000 was found in blood and urine. As the intake of bromide varies from one individual to another, a variation of the bromide level in blood might be expected. When the radioactivities in red cells and plasma were measured in this investigation, the haematocrit method was found to be accurate. For the same person the haematocrit varied less than 3%. The ratio blood cells to serum of bromide ions was found in previous investigations to be 0.75 and 0.55. In the present investigation the corresponding figure was found to be 0.45. As it was found that the bromide ions were not incorporated in fat or proteins of blood, it would seem that the amount of bromide ions inside the red cell membrane is probably distributed mainly in the intracellular water. Theconcentration of 82Br gradually decreased 2-3 hours after application via an exponential course characterized by the biological half-life, which illustrated the continuous exchange of bromide ions in the body caused by different mechanisms. The bromide ions are eliminated from the blood mainly by excretion into the urine. The amount of ammonium bromide administered to the subjects was considered to be sufficiently small not to disturb the physiological distribution.