Ammonium bromide

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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 (powder aerosol)
- Physical state: White crystalline solid
- Analytical purity: 98.5%
- Lot/batch No.: 970027/1
- Stability under test conditions: The stability of the test material was not determined but it is stated in the study that the test material arrived undamaged and in good condition and was used as supplied
- Storage condition of test material: Ambient temperature in the dark

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.