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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Toxicitat von chlor und brom bei eimaliger and wiederholter inhalation.
Author:
M. Schlagbauer and D. Henschler
Year:
1967
Bibliographic source:
Int. Arch. Gewerbepathol. Gewerbehyg. 23:91-98.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Experiment 1:
Groups of 10 female NMRI mice were exposed to concentrations of 110.5 to 315 ppm for 30 min. Mortality was observed up to 10 days post exposureBody weights were determined and lungs of a suitable number of animals were examined for lung edema and histopathological changes after several time intervals.
2. Experiment
Groups of 10 female NMRI mice were exposed for either 3 or 6 h to concentrations of 10, 22, and 40 ppm. The post exposure observation period was up to 10 days.
3. Experiment:
Female NMRI mice (number not stated) were exposed to sublethal bromine concentrations for 8 hours. No mortality was observed, but body weight reduction was followed as an indication of toxicity.
GLP compliance:
no
Test type:
other: acute toxicity after different inhalation times
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Bromine
EC Number:
231-778-1
EC Name:
Bromine
Cas Number:
7726-95-6
Molecular formula:
Br2
IUPAC Name:
dibromine
Details on test material:
not reported

Test animals

Species:
mouse
Strain:
NMRI
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Zenbtralinstitut Versuchstierzucht Hannover
- Weight at study initiation: 18 to 23 gm
- Fasting period before study: no
- Housing: climatised room, 23 deg. C, 50 to 55% relative humidity
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum



ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Details on inhalation exposure:
Bromine vapours were generated from liquid bromine. An air stream was passed over 50 ml of bromine in a 2 l flask at 14 deg. C. The air was further diluted in a mixing chamber. For lower concentrations the temperature was lowered to 10 deg. C and further dilution steps with fresh air were introduced in a cascade principle.
The concentration of bromine in air was determined at higher concentrations by ladign the air-bromine mixture through a 1% potassium iodide solution in 0.1 molar phosphate buffer pH 7.0. The volume was determined in an impinger. The solution was then tritrated with 1 n sodium thiosulfate solution after acidification with 1 ml 1n-H2SO4 under addtion of a 1% starch solution.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
30 min
Concentrations:
111, 40, 199, 236, 252, 268, 290, 315 ppm
No. of animals per sex per dose:
10 female mice per dose
Statistics:
Lichtfield and Wilcoxon 1949

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LC50
Effect level:
174 ppm
95% CL:
144 - 210
Exp. duration:
30 min
Sex:
female
Dose descriptor:
other: mortality
Effect level:
40 ppm
Based on:
test mat.
Exp. duration:
3 h
Remarks on result:
other: 3 of 10 animals died within 10 days
Sex:
female
Dose descriptor:
other: mortality
Effect level:
22 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: 7 of 10 animals died within 10 days
Sex:
female
Dose descriptor:
other: mortality
Effect level:
40 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: 8/10 animald died within 10 days
Sex:
female
Dose descriptor:
other: mortality
Effect level:
22 ppm
Based on:
test mat.
Exp. duration:
3 h
Remarks on result:
other: no deaths
Mortality:
No deaths were seen after 30 minute exposure to 111 ppm for 30 min. 90 to 100% mortality was seen at exposure levels of 236 and higher. The authors calculated a 30 minute LC50 of 174 ppm. Mortality of part of the animals occurred at day 4, day 8 and day 10 post exposure.
In the second experiment exposure of 10 animals for 3 hours with 22 ppm of bromine did not result in mortality, while 40 ppm resulted in a mortality of 3/10 animals. When the animals were exposed to concentrations of 22 and 40 ppm for 6 hours the mortality after 10 days was 7/10 and 8/10 respectively.
In the third experiment animals were exposed for 3 times 8 h to 10 or 5 ppm of bromine. No mortality was observed.
Clinical signs:
other: Local irritation of eyes and respiratory tract (not further specified). Premortal: dyspnea and bronchospasm
Body weight:
Body weight effects were reported for the 3rd experiment. Inhalation of bromine for 3 times 8 hours at concentrations of 5 and 10 ppm resulted in reductions in body weight of 17.7 and 23% respectively.
Gross pathology:
Histopathological changes were necrosis in the mucous membranes of the trachea, desquamation of the bronchial epithelium and bronchioles. in anaimals that died extended alveolar edema was observed. In animals that died more than 16 hours after exposure contracted bronchioles were observed, after 1,5 days or more severe peribronchitic changes and absecesses were observed while the edema was already reversed.
Lung changes were similar in animals exposed to 5 ppm bromine for 3 times 8 hours.

Any other information on results incl. tables

Mortality table based on Schlagbauer and Henschler, 1967, prepared by Oak Ridge National Laboratories in documentation for AEGL value determination, January, 2009

Mortality in Mice Exposed to 111 to 315 ppm of Bromine for 30 minutes

Concentration (ppm)

Mortality

111

0/10

40

3/10

199

6/10

236

9/10

252

10/10

268

9/10

290

10/10

315

10/10

Applicant's summary and conclusion

Interpretation of results:
other: respiratory irritant
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Inhalation of bromine by groups of female NMRI mice led to severe irritation and corrosion of the respiratory tract. Death occurred through lung edema and bronchospasm secondary to the irritation. A 30 min LC50 of 174 ppm was derived. No mortality occurred after 3 hours of expsoure to 22 ppm of bromine, while 7/10 animals died after exposure to 22 ppm of bromine for 6 h. 40 ppm of bromine inhaled for 3 hours led to morrtality of 3/10 animals, while 9/10 animals died after exposure to the same concentration for 6 h. Sublethal concentrations of bromine of 5 and 10 ppm inhaled for 3 times 8 hours led to body weight reductions of 17.7 and 23 % respectively.
Executive summary:

Inhalation of bromine by groups of female NMRI mice led to severe irritation and corrosion of the respiratory tract. Death occurred through lung edema and bronchospasm secondary to the irritation. A 30 min LC50 of 174 ppm was derived. No mortality occurred after 3 hours of expsoure to 22 ppm of bromine, while 7/10 animals died after exposure to 22 ppm of bromine for 6 h. 40 ppm of bromine inhaled for 3 hours led to morrtality of 3/10 animals, while 9/10 animals died after exposure to the same concentration for 6 h. Sublethal concentrations of bromine of 5 and 10 ppm inhaled for 3 times 8 hours led to body weight reductions of 17.7 and 23 % respectively.