Ammonium bromide

Endpoint summary

Description of key information

Oral: The LD50 in this study was determined to be 2868 mg/kg bw (males), 2566 mg/kg bw (females) and 2714 mg/kg bw for both sexes combined.
Inhalation: Under the conditions of this acute inhalation toxicity study performed with a dust aerosol of ammonium bromide and taking into account that no mortalities were observed at the maximum attainable concentration of 0.1 mg/L, ammonium bromide does not have to be classified and labelled with respect to acute inhalation toxicity.
Dermal: The acute dermal LD50 of ammonium bromide was determined to be > 2000 mg/kg. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-06-11 to 1986-07-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, U. K.
- Age at study initiation: 5 weeks
- Weight at study initiation: males 112-143 g and females 110-129 g
- Fasting period before study: 18 hours
- Housing: Type RCI cages of high density polypropylene body, measuring 56 x 38 x 18 cm with stainless steel grid floors and tops.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 25°C
- Humidity (%): 40% - 70%
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 1986-06-11 To: 1986-07-10

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test material was prepared at appropriate concentrations in distilled water to permit administration at a constant volume-dosage of 20 ml/kg bodyweight.
- Amount of vehicle (if gavage): 20 ml/kg bw


MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw

Doses:

2000, 2714, 3684 and 5000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Post-treatment observations at least twice daily during the first 7 days after dosage and daily observations until day 15;
body weight was taken the day before and the day of dosage and then once per week;
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male

Dose descriptor:

LD50

Effect level:

2 868 mg/kg bw

Based on:

test mat.

95% CL:

2 266 - 3 471

Sex:

female

Dose descriptor:

LD50

Effect level:

2 566 mg/kg bw

Based on:

test mat.

95% CL:

2 062 - 3 071

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 714 mg/kg bw

Based on:

test mat.

95% CL:

2 540 - 2 888

Mortality:

There were no deaths among rats treated at 2000 mg/kg ammonium bromide. One male and four female rats treated at 2714 mg/kg died within one hour after dosing. All animals receiving 3684 mg/kg and 5000 mg/kg died between 30 minutes and one day after dosing.

Clinical signs:

other: The most frequent observations were lethargy, decreased motor activity, prone or hunched posture, ataxia and breathing irregularities. Unconsciousness and tonic convulsions were also observed in a smaller number of animals. All survivors receiving 2000 mg

Gross pathology:

The necropsy of animals dying following administration of ammonium bromide revealed fur staining, abnormal gastro-intestinal contents, dark areas on the lungs and occasional thymic petechiae. Animals killed on day 15 showed enlarged cervical lymph nodes in four males and a dark submandibular salivary gland in one male. None of these lesions were considered to be an effect of the test material.

Table 1: Summary of Acute Oral Toxicity

Dose [mg/kg]	Number of dead / number of investigated		Time of death (range) -	Observations -
	Male	Female
2000	0/5	0/5		Lethargic, unconscious, decreased motor activity, hunched, ataxia, prone, musculature tremor, bradypnoea, hyperpnoea, salivation, pigment of snout (duration of signs: 15 minutes – 2 days)
2714	1/5	4/5	½ - 1 hour	Lethargic, unconscious, decreased motor activity, hunched, ataxia, prone, bradypnoea, hyperpnoea, piloerection, ungroomed (duration of signs: 15 minutes – 5 days)
3684	5/5	5/5	½ - 48 hours	Lethargic, unconscious, decreased motor activity, hunched, ataxia, prone, tonic convulsions, bradypnoea, hyperpnoea, piloerection
5000	5/5	5/5	¼ - 1 hour	Prone, gasping
LD50value	2868 mg/kg bw (male); 2566 mg/kg bw (female), 2714 mg/kg bw (combined)

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 in this study was determined to be 2868 mg/kg bw (males), 2566 mg/kg bw (females) and 2714 mg/kg bw for both sexes combined.
In accordance with CLP Regulation (EC) No 1272/2008, ammonium 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 investigate the acute oral toxicity of ammonium bromide in rats. The test material was administered to groups of five male and five female rats as a single oral dose of 2000, 2714, 3684 and 5000 mg/kg at a constant volume of 20 ml/kg in distilled water. Mortality, signs of reaction to treatment and body weight gain were recorded during a subsequent 14-day observation period after which LD50 was determined. Decendents and animals killed on day 15 were subjected to necropsy.

Results and discussion

The principal signs of reaction comprised lethargy, decreased motor activity, prone and hunched posture, ataxia and breathing difficulties. Unconsciousness and tonic convulsions were also observed in a smaller number of animals. Necropsy findings included fur staining, abnormal gastro-intestinal contents, dark areas on the lungs and occasional thymic petechiae. All survivors achieved anticipated bodyweight gains and necropsy findings on day 15 were unremarkable

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

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.

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:

adverse effect observed

Dose descriptor:

LD50

Value:

2 714 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-07-08 to 1997-08-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Limited, Margate, Kent, England
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 161-191 g
- Fasting period before study: None ( fasting during exposure period)
- Housing: 5 x sex per cage - suspended polypropylene cages (58 x 40 x 18 cm) with detachable stainless steel tops and bottoms
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21°C
- Humidity (%): 48 - 68%
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 1997-07-08 To: 1997-08-21

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
- Exposure chamber volume:
- Method of holding animals in test chamber:
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols: RBG-1000 dust generator. Wright Dust Feed Mechanism was used to achieve a stable aerosol
- Method of particle size determination: Marple Cascade Impactor. This device consisted of an in-line sampler and a series of impaction stages (including a back-up filter). The device was capable of fractionating the aerosol into the size range 0.25>7.8 µm
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric method used pressed glass fibre filters (Whatman GF/A, 37 mm). The filter was placed in a conical holder and was positioned and temporarily sealed in a port in the exposure chamber at the animals breathing zone. Chamber air was drawn through the filter at a measured rate of approximately 1 l/min via a gas meter and vacuum pump.
The nominal chamber concentration was estimated from the amount of material and the total air used by the generation system with the following equation:
Measured concentration [mg/l] = weight of material used [mg] / total air flow through system [l]

- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD (mass median aerodynamic diameter): 2.61 µm
+ GSD (geometric standard deviation): 3.204

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Maximum attainable concentration

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric measure

Duration of exposure:

4 h

Concentrations:

Nominal concentration: 37.96 mg/L
Measured concentration: 0.1 mg/L (maximum attainable concentration)

No. of animals per sex per dose:

5/sex/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rats were observed continously throughout each exposure period, and any clinical signs noted were recorded at 30 min intervals. Animals were also observed immediately after exposure and for the first 1-2 h post dosing and thereafter at least once daily during the 14 day study period. Body weight was taken immediately before dosing and on Days 2, 3, 4, 7,10 and 14 post exposure
- Necropsy of survivors performed: yes
- Other examinations performed: organ weights - The lungs of each animal were removed and weighed to allow calculation of lung to body weight ratio.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.1 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: at the maximum attainable concentration of 0.1 mg/L, no mortalities were observed.

Mortality:

No mortalities

Clinical signs:

other: During exposure: slight reductions on respiratory rates were noted in response to the test material. During observation period: rats were observed to be wet and unkempt and have staining on head. These signs were considered related to restraint and not o

Body weight:

There were no effects on body weights considered to be related to treatment with the test material.

Gross pathology:

There were no findings at necropsy considered to be related to treatment with the test material.

Table 1: Summary of results

Dose [mg/L]	Number of dead / number of investigated	Time of death (range)	Observations
0.1 mg/L	0/10	-	All animals were wet/unkempt and four rats (two male and two female) showed staining on head immediately post exposure. These signs were gone 1-2 hours post exposure and no further signs were noted.
LD50value > 0.10 mg/L

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this acute inhalation toxicity study performed with a dust aerosol of ammonium bromide and taking into account that no mortalities were observed at the maximum attainable concentration of 0.1 mg/L, ammonium bromide does not have to be classified and labelled with respect to acute inhalation toxicity.

Executive summary:

Materials and Methods

The study was undertaken to investigate the acute inhalation toxicity of aerosolized ammonium bromide in rats. Five male and five female rats were exposed to a single 4 h snout only exposure of 0.1 mg/L (maximum attainable concentration) of test substance and were observed for clinical signs for a period of 14 days post-exposure. Individual bodyweights were taken on the day before dosing and on Day 2, 3, 4, 7,10 and 14 post treatment. All animals were subjected to necropsy at termination of the study. Lungs were removed and weight taken to allow calculation of lung to body weight ratio.

Results and discussion

Rats exposed to a test atmosphere containing aerosolized ammonium bromide at a concentration of 0.1 mg/L by snout inhalation for a period of 4 hours showed minimal evidence of toxicity and no mortalities were observed. During exposure rats were observed to have slight reductions in respiratory rates. This is consistent with exposure to any irritant dust atmosphere and restraint in a tube. During the observation period rats were observed to be wet and unkempt and have staining on head for a short period after exposure. This was considered consistent with restraint in tubes and not specifically related to exposure to the test material.

There were no effects on body weights considered to be due to treatment with the test material.

There were no necropsy findings considered to be related to treatment with the test material.

There were no effects on lung to body weight ratios considered to be related to treatment with the test material.

The maximum attainable concentration of 0.1 mg/L was considered to be relatively low. The poor stability of the aerosol at this concentration and the 64.4% aerosol mass < 4 µm resulted in an extremely low respirable fraction. These characteristics were expected from the difficulties observed during optimisation and supported by the high nominal concentration obtained in attempting to aerosolise the test material.

The unusually high value of nominal concentration (37.96 mg/L) relative to the measured aerosol concentration (0.1 mg/L) indicates that a substantial fraction of the test material would not readily aerosolise. The losses are typically due to sedimentation within the exposure chamber. Non-volatile test materials such as this which do not readily aerosolise tend to present low inhalation hazards. Under the conditions of this acute inhalation toxicity study performed with a dust aerosol of ammonium bromide and taking into account that no mortalities were observed at the maximum attainable concentration of 0.1 mg/L, ammonium bromide does not have to be classified and labelled with respect to acute inhalation toxicity.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-08-05 to 1997-09-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Test material was spread over 5 % of body surface (4 cm x 6 cm) instead of 10%.

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Version / remarks:

Sub-Division F

Deviations:

yes

Remarks:

Test material was spread over 5 % of body surface (4 cm x 6 cm) instead of 10%.

Qualifier:

according to guideline

Guideline:

other: EEC Directive 92/69/EEC, Annex V, Test B3, July 1992

Deviations:

yes

Remarks:

Test material was spread over 5 % of body surface (4 cm x 6 cm) instead of 10%.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK, Shaw´s Farm, Blackthorn, Bicester, OX6 0TP
- Age at study initiation: 8-10 weeks
- Weight at study initiation: males: 256- 290 g, females: 213-262 g
- Fasting period before study:
- Housing: Individually in suspended polypropylene cages (42 x 27 x 20 cm) with stainless steel tops and bottoms
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20°C
- Humidity (%): mean: 62%
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 1997-08-05 To: 1997-09-09

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 4 cm x 6 cm
- % coverage: approximately 5 % of body surface
- Type of wrap if used: water moistened patches


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Sterile distilled water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dose Ranging: 500, 1000, 1500 and 2000 mg/kg bw
Limit Test: 40 mg/cm2 (comparable to 2000 mg/kg bw)
- Constant volume or concentration used: yes (Limit Test)

VEHICLE
Substance was applied as supplied; no vehicle used.

Duration of exposure:

24 hours

Doses:

Dose Ranging: 500, 1000, 1500 and 2000 mg/kg bw
Limit Test: 40 mg/cm2 (comparable to 2000 mg/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 reaction of treatment and viability were performed at least once per day for up to 14 days after dosing. Bodyweights were recorded on Day 1,8 and 15 during the main study. For dose ranging body weight was recorded on the day of dosing only.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical observations were conducted frequently on the day of dosing and daily thereafter until sacrifice on Day 8 (Dose Ranging) or Day 15 (Main Study).

Statistics:

No statistical analysis performed

Preliminary study:

There were no premature deaths and no clinical signs noted throughout the observation period of the dose ranging study and in addition, no necropsy findings noted .

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No animals died prematurely.

Clinical signs:

other: Loose faeces (1 male, 2 female) and wet perigenital (1 female) on Day 1 and red test side (1 male, 1 female) on Day 2.

Gross pathology:

no necropsy findings noted

Table A6.1.2/01-1                    Summary of Acute Dermal Toxicity
Dose Level [mg/kg] / sex	Number of dead / number of investigated		Observations
2000/ male	0/5		Test side slightly red, few loose faeces
2000/ female	0/5		Test side slightly red, few loose faeces, wet pergenital area
LD50value	> 2000 mg/ kg bw

 

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute dermal LD50 of ammonium bromide was determined to be > 2000 mg/kg. In accordance with CLP Regulation (EC) No 1272/2008, no classification and labelling with respect to acute dermal toxicity is required.

Executive summary:

Materials and Methods

This study investigated the acute dermal toxicity of ammonium bromide after a single dermal administration to rats. Five male and five female rats were exposed to a 24 h dermal application of 2000 mg/kg of test substance, which was applied as supplied under occlusive water moistened patches onto skin which was clipped the day before. The animals were observed daily for reaction to treatment for up to 14 days after dosing.

Results and Discussion

Clinical signs were limited to loose faeces and wet perigenital on Day 1, and a red test side on Day 2. Application of ammonium bromide did not show influence on body weight gain. There were no premature decendents during the study and no necropsy findings noted.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

other: 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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

Oral

In a key study performed to OECD 401 ammonium bromide was administered to groups of five male and five female rats as a single oral dose of 2000, 2714, 3684 and 5000 mg/kg at a constant volume of 20 ml/kg in distilled water. Mortality, signs of reaction to treatment and body weight gain were recorded during a subsequent 14-day observation period after which LD50 was determined. Decendents and animals killed on day 15 were subjected to necropsy.

The principal signs of reaction comprised lethargy, decreased motor activity, prone and hunched posture, ataxia and breathing difficulties. Unconsciousness and tonic convulsions were also observed in a smaller number of animals. Necropsy findings included fur staining, abnormal gastro-intestinal contents, dark areas on the lungs and occasional thymic petechiae. All survivors achieved anticipated bodyweight gains and necropsy findings on day 15 were unremarkable

The LD50 in this study was determined to be 2868 mg/kg bw (males), 2566 mg/kg bw (females) and 2714 mg/kg bw for both sexes combined.

 

Inhalation

The study was undertaken to investigate the acute inhalation toxicity of aerosolized ammonium bromide in rats. Five male and five female rats were exposed to a single 4 h snout only exposure of 0.1 mg/L (maximum attainable concentration) of test substance and were observed for clinical signs for a period of 14 days post-exposure. All animals were subjected to necropsy at termination of the study. Lungs were removed and weight taken to allow calculation of lung to body weight ratio.

There was minimal evidence of toxicity and no mortalities were observed. During exposure rats were observed to have slight reductions in respiratory rates, consistent with exposure to any irritant dust atmosphere and restraint in a tube. During the observation period rats were observed to be wet and unkempt and have staining on head for a short period after exposure. This was considered consistent with restraint in tubes and not specifically related to exposure to the test material.

There were no effects on body weights considered to be due to treatment with the test material.

There were no necropsy findings considered to be related to treatment with the test material.

There were no effects on lung to body weight ratios considered to be related to treatment with the test material.

The maximum attainable concentration of 0.1 mg/L was considered to be relatively low. The poor stability of the aerosol at this concentration and the 64.4% aerosol mass < 4 µm resulted in an extremely low respirable fraction.

The unusually high value of nominal concentration (37.96 mg/L) relative to the measured aerosol concentration (0.1 mg/L) indicates that a substantial fraction of the test material would not readily aerosolise. Under the conditions of this acute inhalation toxicity study performed with a dust aerosol of ammonium bromide and taking into account that no mortalities were observed at the maximum attainable concentration of 0.1 mg/L, ammonium bromide does not have to be classified and labelled with respect to acute inhalation toxicity.

 

Dermal

This study investigated the acute dermal toxicity of ammonium bromide after a single dermal administration to rats. Five male and five female rats were exposed to a 24 h dermal application of 2000 mg/kg of test substance, which was applied as supplied under occlusive water moistened patches onto skin which was clipped the day before. The animals were observed daily for reaction to treatment for up to 14 days after dosing.

Clinical signs were limited to loose faeces and wet perigenital on Day 1, and a red test side on Day 2. Application of ammonium bromide did not show influence on body weight gain. There were no premature decendents during the study and no necropsy findings noted.

Under the conditions of the study, the acute dermal LD50 of ammonium bromide was determined to be > 2000 mg/kg.

Other

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.

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

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).