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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: EPA FIFRA 81-1
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium bromide
EC Number:
231-599-9
EC Name:
Sodium bromide
Cas Number:
7647-15-6
Molecular formula:
NaBr
IUPAC Name:
Active bromine generated from sodium bromide and sodium hypochlorite
Details on test material:
- Name of test material (as cited in study report): Active ingredient ´Sodium bromide, technical grade (99,23 %)
- Description: White powder
- Analytical purity: 99.23 %
Ammonium bromide is an inorganic salt that dissociates to its composite ions in aqueous solutions at environmental pH and temperature. Comparison of the available data on the various bromide salts have shown that the bromide ion is the relevant ion for determination of the toxicological profile with simple cations such as potassium, sodium or ammonium, that are ubiquitous in nature, having little or no influence on the bromide ion properties. It is therefore justified to read-across data from other inorganic bromide salts to ammonium bromide.
- Lot/batch No.: Batch No.: 7320
- Stability under test conditions: not determined

Test animals

Species:
rat
Strain:
other: CD [Crl: CD(SD)BR]
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River U. K. Limited, Margate, Kent, England
- Age at study initiation: six weeks
- Weight at study initiation: 112 to 150 g


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1 % aqueous methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Sodium bromide was prepared at various concentrations in 1% aqueous methylcellulose and administered at a volume of 20 ml/kg.
- Amount of vehicle (if gavage): 20 ml/kg bodyweight



MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bodyweight


Doses:
Preliminary study: 2 g/kg bw and 5 g/kg bw
Main Study: 3.2 g/kg bw, 4 g/kg bw and 5 g/kg bw
No. of animals per sex per dose:
5/sex/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs and mortality soon after dosing and at frequent intervals for the remainder of day 1. On subsequent days the animals were observed twice daily for 5 (preliminary study) and 14 days (main study) respectively.
Individual bodyweights of rats were taken on Days 1 (day of dosing), 8 and 15 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight; A pre-test was carried out to establish a dosing regimen using groups of two male and two female rats at two dose levels of 2 and 5 g/kg bodyweight. Animals were observed for mortality and clinical signs for 5 days.

Results and discussion

Preliminary study:
The results indicated that the acute median lethal oral dose of sodium bromide, technical grade, was greater than 5 g/kg bodyweight for male rats and between 2 and 5 g/kg bodyweight for female rats.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4.2 other: g/kg bw
Mortality:
Two female rats dosed at 5 g/kg bodyweight died on Day 4 of preliminary study. All other animals survived during the study period of five days.
During the main study there were deaths amongst rats of both sexes dosed at 4 and 5 g/kg. Deaths occurred from Day 3 to Day 7. One male was sacrificed after being found moribund on Day 5.
Clinical signs:
other: Signs of reaction to treatment observed were recorded for animals in the main study only. All treated animals showed piloerection within 5 minutes of dosing and abnormal body carriage (hunched posture), abnormal gate (waddling), lethargy, decreased respir
Gross pathology:
Autopsy of rats that died commonly revealed slight congestion of the glandular region of the stomach; red coloured fluid was observed in the urinary bladder of a single male (4 g/kg); isolated cases of congestion or vascular congestion of other zones of the gastrointestinal tract.
Terminal autopsy findings of rats killed at the end of the study, were normal.

Any other information on results incl. tables

Table A6.1.1/02-1           Summary of Acute Oral Toxicity

Dose g/kg

Number of dead /
number of investigated

Time of death (range)

Observations

male

female

3.2

0/5

0/5

-

Piloerection, hunched posture, waddling, lethargy, decreased respiratory rate, ptosis, pallor of extremities, prostrate

4

1/5

3/5

Day 5-7

Piloerection, hunched posture, waddling, lethargy, decreased respiratory rate, ptosis, pallor of extremities, ataxia, prostrate

5

4/5

5/5

Day 3-6

Piloerection, hunched posture, waddling, lethargy, decreased respiratory rate, ptosis, pallor of extremities, ataxia, prostrate, moribund (apathy, prostrate, cyanosis, decreased respiration)

LD50 value

4.5 g/kg bw (males), 3.9 g/kg bw (females), 4.2 g/kg bw (combined)

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 was determined to be 4.5 g/kg bw (males), 3.9 g/kg bw (females) and 4.2 g/kg bw (both sexes combined). In accordance with CLP Regulation (EC) No 1272/2008, sodium bromide does not have to be classified and labelled with respect to acute oral toxicity.
Executive summary:

Materials and methods

The study was designed to assess the toxicity following a single oral dose of sodium bromide. Groups of 5 fasted CD rats received a single oral dose of the test substance formulated in 1 % aqueous methylcellulose and administered at a volume of 20 ml/kg and dose levels of 3.2; 4 and 5 g/kg bw. Animals were observed for mortality and clinical signs soon after dosing, at frequent intervals for the remainder of day 1 and twice daily on the subsequent days. Body weights were taken on Day 1, 8 and 15 and at death. All animals were subject to necropsy and LD50 was determined.

Results and discussion

Signs of reaction observed were piloerection, abnormal body carriage, abnormal gait, lethargy, decreased respiratory rate, ptosis, pallor of the extremities, ataxia and prostration. There were death amongst rats of both sexes dosed at 4 and 5 g/kg. Autopsy of these rats revealed slight congestion of the glandular region of the stomach; red coloured fluid was observed in the urinary bladder of a single male (4 g/kg) and isolated cases of congestion or vascular congestion of other zones of the gastrointestinal tract were observed. Low bodyweight gains were recorded for surviving rats at all dose levels. Body weight losses were recorded for all rats that died.