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Description of key information

Oral: The LD50 was determined to be > 2000 mg/kg bw
Dermal: The acute dermal LD50 was determined to be > 2000 mg/kg bw.
Inhalation: The substance is not volatile and is not inhalable.

Key value for chemical safety assessment

Acute toxicity: via oral route

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


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.
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.
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:
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 respiratory gate, ptosis and pallor of the extremities within three hours of dosing. Other reactions first observed at, or later than three hours were: ataxia (all rats dosed 4 g/kg and above) and prostration (one female rat dosed 3.2 g/kg, most rats dosed at 4 g/kg and all rats dosed at 5 g/kg)
Body weight:
Low bodyweight gains, and in one case a bodyweight loss, were recorded on day 8 for rats at all dose levels. Anticipated bodyweight gains were achieved during the second week of the study. Body weight losses were recorded for all rats that died
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.

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)

 

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
other: EPA FIFRA 81-6
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Froxfield Rabbits, Petersfield, Hampshire, England
- Age at study initiation: 9-13 weeks
- Weight at study initiation: 2090-2900 g
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- % coverage: 10 % of body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Warm water (30-40°C)
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g/kg bw
- Concentration (if solution): the test substance was moistened at 1 mL/kg with distilled water
- Constant volume or concentration used: yes
- For solids, paste formed: yes; the test substance was moistened at 1 mL/kg with distilled water


VEHICLE
- Amount(s) applied (volume or weight with unit): 1 mL
Duration of exposure:
24 hours
Doses:
2 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: Observation for clinical signs and dermal irritation soon after dosing, then at frequent intervals for the remainder of Day 1. On subsequent days the animals were examined at least twice for 14 days. Body weights were taken on Day 1, 8 and 15 and at death.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One male rabbit was found dead on Day 2. There were no clinical signs recorded prior to death. A slight loss in bodyweight was recorded. Autopsy revealed congestion of the lungs. No other macroscopic abnormalities were observed. The death of this animal was not considered to be treatment related.
Clinical signs:
There were no clinical signs of toxicity seen in any of the treated animals including those found dead. No dermal irritation was observed at the treated skin sites of any of the animals throughout the fourteen day study.
Body weight:
A slightly low body weight gain was recorded for one of the female rabbits in the first week of the study. All other animals achieved anticipated bodyweight gains.
Gross pathology:
One rabbit showed small pale areas on the liver. Some of these contained a purulent material. One male rabbit that died during the study showed congestion of the lungs. Terminal autopsy findings of all other rabbits were normal.

 

Table A6.1.2/02-1                          Summary of Acute Dermal Toxicity

Dose [g/kg] / sex

Number of dead /
number of investigated

Time of death (range)

Observations

2 / male

1/5

Day 2

No treatment related observations

2 / female

0/5

 

No treatment related observations

LD50value

> 2 g/kg body weight

 

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 in male and female rabbits was determined to be greater than 2000 mg/kg. In accordance with CLP Regulation (EC) No 1272/2008, sodium bromide does not have to be classified and labelled with respect to acute dermal toxicity.
Executive summary:

Materials and Methods

The study was designed to assess the dermal toxicity of sodium bromide. Five male and five female rabbits were exposed to a single dermal dose of 2 g/kg bodyweight sodium bromide moistened at 1 mL/kg with distilled water. The treated skin area was clipped the day before. Animals were observed daily for mortality and clinical signs for dermal irritation and toxicity. Body weights were recorded once per week. Autopsy was performed for all rabbits at termination of the study.

Results and Discussion

No clinical signs or dermal irritation was observed at the treated skin sites of both surviving and decedent animals. A slightly low body weight gain was recorded for one of the female rabbits in the first week of the study. All other animals achieved anticipated bodyweight gains. One male rabbit was found dead on Day 2. Autopsy revealed congestion of the lungs. No other abnormalities were observed and there were no clinical signs recorded prior to death. The death of this animal was not considered to be treatment related.

The LD50 >2000 mg/kg bw (both sexes) (equivalent to: >1552 mg (Br-)/kg bw (both sexes)).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Oral

In a key study performed to OECD 401 5 rats/sex/dose group were each given a single dose of sodium bromide by gavage in 20 mL of 1 % aqueous methylcellulose. Clinical observations were made over the following 14 days including weekly bodyweight measurements. At death during the study period, or sacrifice at study termination, the animals were subjected to a macroscopic post mortem examination. An LD50 was determined from the observation data. Females: 3900 mg/kg bw, males: 4500 mg/kg bw (equivalent to females: 3028 mg (Br-)/kg bw, males: 3492 mg (Br-)/kg bw) Males + females combined: 4200 mg/kg bw (equivalent to: 3260 mg (Br-)/kg bw)

Inhalation

The bromide ion is not a volatile species [vapour pressure value of 1.8 x 10-6 Pa] with a high water solubility (946000 mg/L at 25 °C) so it remain in the water phase when solubilised during use. The particle size distribution indicates that it will not be available for inhalation with particle size > 100 µm.

Dermal

In a key study 5 Rabbits/sex were each given a single application of 2000 mg/kg bw the test substance moistened with 1 mL/kg water. Clinical observations were made over the following 14 days including weekly bodyweight measurements. At death during the study period, or sacrifice at study termination, the animals were subjected to a macroscopic post mortem examination. An LD50 was determined from the observation data.

No clinical signs or dermal irritation was observed at the treated skin sites of both surviving and decedent animals. A slightly low body weight gain was recorded for one of the female rabbits in the first week of the study. All other animals achieved anticipated bodyweight gains. One male rabbit was found dead on Day 2. Autopsy revealed congestion of the lungs. No other abnormalities were observed and there were no clinical signs recorded prior to death. The death of this animal was not considered to be treatment related.

The LD50 >2000 mg/kg bw (both sexes) (equivalent to: >1552 mg (Br-)/kg bw (both sexes)).

Justification for classification or non-classification

Sodium bromide is not acutely toxic by the oral or dermal routes (Oral LD50 = 4200 mg/kg, dermal LD50 >2000 mg/kg).

The inhalation study of sodium bromide is scientifically unjustified, since the bromide ion has a very low volatility based on the vapour pressure of 1.8 x 10-6Pa (Cowlyn T.C., 1991) and has a particle size which excludes inhalation (> 100 µm). Therefore exposure to significant quantities of bromide ions by direct inhalation is not likely to occur.

Based on the experimental results, sodium bromide is not classified for acute toxicity by the oral or dermal routes.

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