Sodium bromide

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test method equivalent or similar to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents).

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

(The number of animals included in the study is not specified; clinical chemistry and ophtalmoscopic examinations were not performed).

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium bromide

EC Number:

231-599-9

EC Name:

Sodium bromide

Cas Number:

7647-15-6

Molecular formula:

BrNa

IUPAC Name:

Active bromine generated from sodium bromide and sodium hypochlorite

Details on test material:

- Name of test material (as cited in study report): sodium bromide

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days.

Frequency of treatment:

Daily.

Doses / concentrations

Remarks:

Doses / Concentrations:
75, 300, 1200, 4800, 19200 mg/kg diet.
Basis:
nominal in diet

No. of animals per sex per dose:

No data.

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes.

HAEMATOLOGY: Yes.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (organs examined: musculature, thyroid, prostate and adrenals).
HISTOPATHOLOGY: Yes (organs examined: musculature, thyroid, prostate and adrenals).

Statistics:

No data.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

(in the 19,200 mg/kg diet group)

Mortality:

mortality observed, treatment-related

Description (incidence):

(in the 19,200 mg/kg diet group)

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

(in the 19,200 mg/kg diet group)

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

(in the 19,200 mg/kg diet group)

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

(in the 19,200 mg/kg diet group)

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

(in females exposed to ≥1200 mg/kg and in males exposed to ≥4800 mg/kg)

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

(in the highest dosage groups)

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
Depressed grooming and motor incoordination of the hind legs were observed at the highest dose level. These effects may have been due to a disturbance of the central nervous system by bromide.

BODY WEIGHT AND WEIGHT GAIN
A significant growth retardation was observed in both sexes fed 19,200 mg/kg diet.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
The highest dosage group (19,200 mg/kg diet) showed a slight decrease in food conversion.

HAEMATOLOGY
A slight decrease in the concentration of lymphocytes and a doubling in the concentration of neutrophilic granulocytes were found in both sexes of the 19,200 mg/kg diet group. The increase in neutrophilic granulocytes may be regarded as a stress-mediated effect, although it cannot be excluded that the effect was originated from a bacterial infection as a result of the bad physical condition of the animals. The effect on the lymphocytes may be suggestive of a slight suppressive effect on the immune system by bromide.

ORGAN WEIGHTS
The most prominent effects were on the thyroid and the gonads. The relative weight of the thyroid was increased in females from exposed to ≥1200 mg sodium bromide/kg diet and in males at the highest dose level (19,200 mg/kg diet). Males exposed to 4800 and 19200 mg/kg diet showed a decrease in the relative prostate weight.

HISTOPATHOLOGY: NON-NEOPLASTIC
A complex of histopathological changes was observed in the endocrine system. A no-effect level of 300 mg/kg diet was established on the basis of the effects on the thyroid. A remarkable thyroid activation was found for both sexes in the highest dose group. In addition, a decrease in spermatogenesis and a decrease in vacuolization of the zona fasciculata in the adrenals were observed in males. Furthermore, females showed a decrease in the number of corpora lutea.

Effect levels

Dose descriptor:

NOAEL

Effect level:

300 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: (equivalent to 30 mg/kg bw/day for young rats and 15 mg/kg bw/day for older rats). Based on thyroid effects.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Effect levels:

The effect levels were reported as Concentration of the substance in feed (mg/kg diet). In order to express the dose levels as mg/kg Body Weight Per Day, a conversion factor of 0.1 for young rats and 0.05 for older rats were used (in accordance with the OECD Environment, Health and Safety Publications Series on Testing and Assessment No.51, Paris, 2006).

Applicant's summary and conclusion

Conclusions:

The NOAEL after 90 days oral exposure to sodium bromide was determined to be 300 mg/kg diet (equivalent to 30 mg/kg bw/day for young rats and 15 mg/kg bw/day for older rats), on the basis of the effects on the thyroid.

Executive summary:

A subchronic oral toxicity study was performed with sodium bromide following a method equivalent or similar to OECD Guideline 408. Wistar male and female rats were exposed to the test substance at dietary concentrations of 75, 300, 1200, 4800 and 19,200 mg sodium bromide/kg diet in a 90 -day test. Clinical observations, body weight and food consumption determinations, as well as haematological examinations were performed throughout the test. At the end of the study gross pathology and histopathology examinations were performed in the musculature, the thyroid, the prostate and the adrenal glands. Depressed grooming and motor incoordination of the hind legs were observed only in the highest dose level. These effects may had been due to a disturbance of the central nervous system by bromide levels. A significant growth retardation was also observed in both sexes in the 19,200 mg/kg diet dosage group, along with a slight decrease in food conversion. In the haematologic evaluation performed, a slight decrease in the concentration of lymphocytes and a doubling in the concentration of neutrophilic granulocytes were found in both sexes. The most prominent effects were on the thyroid and the gonads. The relative weight of the thyroid was increased in females exposed to ≥1200 mg sodium bromide/kg diet and in males at the highest dose level (19,200 mg/kg diet). Males exposed to 4800 and 19,200 mg/kg diet showed a decrease in the relative prostate weight. These changes were confirmed by the observation of a complex of histopathological changes in the endocrine system. A remarkable thyroid activation was found for both sexes in the highest dose group. In addition, a decrease in the spermatogenesis and a decrease in the vacuolization of the zona fasciculata in the adrenals were observed in males. Furthermore, females showed a decrease in the number of corpora lutea. The NOAEL after 90 days oral exposure to sodium bromide was determined to be 300 mg/kg diet (equivalent to 30 mg/kg bw/day for young rats and 15 mg/kg bw/day for older rats), on the basis of the effects on the thyroid.