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Administrative data

Description of key information

Acute toxicity, oral: 
Key study: Study well documented, meets generally accepted scientific principles, acceptable for assessment. The oral LD50 in mice is 4300 mg/kg bw.
Supporting study: Documentation insufficient for assessment. Only few data on test method reported. The oral LD50 in male rats is > 5000 mg/kg bw.
Acute toxicity, inhalation:
Key study: Study well documented, meets generally accepted scientific principles, acceptable for assessment. The inhalative LC50 in mice is 12 mg/l (12171.05 mg/m3).
Key study: Study well documented, meets generally accepted scientific principles, acceptable for assessment. The LC0 (after a 7-hour exposure period) and LC100 (after a 6-hour exposure period) for bromochloromethane was determined to be 5,000 ppm (or 26458.81 mg/m3) and 10,000 ppm (or 52917.63 mg/m3), respectively.
Acute toxicity, dermal:
Supporting study: Only few data on test method reported. The dermal LD50 of bromochloromethane is determined to be > 5000 mg/kg bw.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Principles of method if other than guideline:
Single gavage and 10 day repeated dose toxicity study.
GLP compliance:
no
Limit test:
no
Species:
mouse
Strain:
Swiss
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 20 g
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50%
Doses:
Single dose (three series of mice): 500, 3,000, 4,500 mg/kg.
One to ten day repeated dose (a fourth series of mice): 3,000 mg/kg.
No. of animals per sex per dose:
225 mice altogether.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes. Several representative mice from the three series were killed for histologic examination at intervals following the single dose, and several from the fourth series, following each of the one to ten doses. Some of the mice that died were also examined.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
4 300 mg/kg bw
Based on:
test mat.
Gross pathology:
Pathological findings in the liver and kidneys were found in mice given a single dose of 3,000 and 4,500 mg/kg. A slight cardiac fatty degeneration was also found in one mouse given 3,000 mg/kg. Besides, the adrenal glands examined exhibited signs of lipoid deplation of the cortex. In the series of mice given multiple doses of 3,000 mg/kg, the lesions were more frequent, severe and prolonged than after a single dose.

Frequency and severity of changes after a single dose: No significant changes were noted after administration of 500 mg/kg of the test substance. After a single dose of 3,000 and 4,500 mg/kg, fatty degeneration of the liver and the kidney was slight or absent in mice that died three or four hours later, was usually severe in the mice killed twenty-four hours later, but was generally not found in those surviving forty-eight hours or longer. Twelve of fifty mice that died or were killed within forty-eight hours showed subcapsular necrosis of the liver, and 5 showed some hydropic liver cells; slight similar changes were seen in one of five mice killed ninety-six hours after receiving the compound. Eight of 32 mice that were killed or died within twenty-four hours after administration of the compound showed hemoglobin casts in a few renal tubes; 7 of these mice received 4,500 mg/kg, and 1 of the 7 showed epithelial necrosis in a few scattered convulted renal tubules. Slight cardiac fatty degeneration was found in only 1 mouse, which died within twenty-four hours after a dose of 3,000 mg/kg. The few adrenal glands examined showed indications of transient lipoid deplation of the cortex.

Frequency and severity of changes after consecutive daily doses: In the series of mice given multiple doses of 3000 mg/kg, the lesions were more frequent, severe and prolonged than after a single dose. 24 to 48 hours after the initial dose, fatty degeneration occurred in the liver, the kidney and less frequently in the heart. It was slight or absent after eighty hours. Twenty-three of 32 mice that died or were killed within seventy-two hours after the initial dose showed subcapsular necrosis of the liver, 8 showed hydropic degeneration and 8 showed a slight to moderate increase of mononuclear cells periportally. Such changes were infrequent after three days and were not seen in mice killed more than five days after the initial dose. One mouse killed nine days after the initial dose showed a few focal and centrolobular areas of coagulation necrosis of the liver cells. Hemoglobin casts were seen in this series in only 1 animal, which died in forty-eight hours, shortly after the third daily dose. Another mouse, which died twenty-four hours after the sixth daily dose, showed extensive tubular necrosis of the inner cortical zone of the kidney. Slight pneumonitis was found in nearly all groups. Cloudiness of the eyes was observed in only 2 of 11 mice that died six hours after the second dose and in 3 of 8 mice that died shortly after the third daily dose of 3,000 mg/kg. It was found in 2 of 8 mice that died after a second daily dose of 4,500 mg/kg.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 in mice is 4300 mg/kg bw.
Executive summary:

A single gavage and 10 day repeated dose toxicity study was performed with the test substance bromochloromethane. 50% of bromochloromethane in olive oil was administered by stomach tube to several series of white Swiss mice. Three series of mice were given a single dose of 500, 3,000 and 4,500 mg/kg, respectively, and a fourth series was given 3,000 mg/kg on one to ten consecutive days. The control group received olive oil only. Several representative mice from each series were killed for histologic examination and some of the mice that died were also examined. Fatty degeneration of the liver and kidney, as well as focal necrosis and hydropic degeneration of the liver was observed in the 3,000 and 4,500 groups after single oral dose. Changes were most severe after 24 hours and were reversible in mice surviving 48 hours. No effects were noted at 500 mg/kg. In the series of mice given multiple doses of 3000 mg/kg, the lesions were more frequent, severe and prolonged than after a single dose. The oral LD50 in mice was determined to be 4300 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 300 mg/kg bw
Quality of whole database:
One Key study with Klimish score = 2 and one Supporting study with Klimish score = 3 are available.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Principles of method if other than guideline:
Single inhalation and 5-day repeated dose toxicity study.
GLP compliance:
no
Limit test:
no
Species:
mouse
Strain:
Swiss
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 20 g
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The animals were exposed to the test substance in an inhalation chamber according to the procedure described by Werner, H.C., Mitchell, J.L., Miller, J.W., and von Oettingen, W.F. (1943).
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
7 h
Remarks on duration:
(on one to five successive days)
Concentrations:
7 to 17 mg/l.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 72 hours.
- Necropsy of survivors performed: yes. Several mice of each series were killed for histologic study immediately and at intervals following completion of each of the one to five exposures. 79 mice were examined in total.
Sex:
not specified
Dose descriptor:
LC50
Effect level:
12 mg/L air
Based on:
test mat.
Exp. duration:
7 h
Remarks on result:
other: (equiv. to 12171.05 mg/m3)
Clinical signs:
other: Nearly half the mice that died during or soon after a single inhalation exposure showed a whitish opacity of one or both eyes. This opacity appeared shortly before death and usually involved the entire cornea. It was not observed in mice that appeared to
Gross pathology:
The chief pathologic changes observed were marked visceral congestion, fatty degeneration of the liver, the kidney and occasionally of the heart, lipoid depletion of the inner portion of the adrenal cortex, interstitial pneumonitis and opacity of one or both eyes. Less frequent lesions were tubular necrosis and hemoglobin casts in the kidney. Fatty degeneration of the liver was the commonest and earliest lesion (observed after only a few hours' exposure and at 7 mg/l concentration). Fatty degeneration of the kidney was not seen in mice after a single seven hour exposure to 7 mg/l but was moderately severe in nearly all mice dying after a seven hour exposure to 12 mg/l concentration. Pneumonitis was not extensive and occurred in mice exposed daily between 24 and 72 hours after the end of the first exposure. One of 2 mice that died twenty-eight hours after the onset of a seven hour exposure to 17 mg/l showed hemoglobin casts in many scattered convulted tubules, and a few such tubules showed necrosis of some or all of their lining epithelial cells. Slight similar changes were seen in a few other exposed mice. In the heart, slight fatty degeneration occurred focally only in occasional exposed animals. Histologic examination of the opaque eyes observed in some animals showed foci of disorganization and edema in the substantia propria of the cornea with absence of the anterior epithelium or the posterior endothelium in some areas. The anterior chamber often contained some eosinophilic serous material or occasionally some polymorphonuclear and mononuclear cells.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The inhalative LC50 in mice is 12 mg/l (12171.05 mg/m3).
Executive summary:

A single inhalation and 5 day repeated dose toxicity study was performed with the test substance bromochloromethane. Swiss mice were exposed to bromochloromethane for seven hours on one to five successive days to concentrations ranging from 7 to 17 mg/l. Several mice were killed for histologic study immediately and at intervals following completion of each of the one to five exposures. Marked visceral congestion, fatty degeneration of the liver, the kidney and occasionally of the heart, lipoid depletion of the inner portion of the adrenal cortex, interstitial pneumonitis and opacity of one or both eyes were observed. Less frequent lesions were tubular necrosis and hemoglobin casts in the kidney. It was found that the LC50 concentration was 12 mg/l (equivalent to 12171.05 mg/m3).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
12 171.05 mg/m³
Quality of whole database:
Two Key study with a Klimish score = 2 are available.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Only few data on test method reported.
Principles of method if other than guideline:
Acute dermal toxicity study using a modified Draize technique.
GLP compliance:
no
Test type:
other: not specified.
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours.
Doses:
5000 mg/kg
No. of animals per sex per dose:
4 rabbits.
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived after the administration of 5000 mg/kg bw.
Clinical signs:
Burn and denaturation of the skin was observed in the exposed animals.
Body weight:
A slight loss of body weight was observed during the observation period.
Gross pathology:
Not examined.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 of bromochloromethane is determined to be > 5000 mg/kg bw.
Executive summary:

In the present acute dermal toxicity study conducted with the test substance bromochloromethane, belly hair was clipped from the rabbits and a single application of the test substance was applied using a modified Draize technique. Four out of four rabbits survived a dose of 5000 mg/kg, and only a slight loss of body weight occurred over the observation period. Clinical observations included a burn and denaturation of the skin with occlusive application. On the basis of these results, the dermal LD50 of bromochloromethane is determined to be > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Only one study is available (Supporting study with Klimish score = 3).

Additional information

Acute toxicity, oral:

Key study: A single gavage and 10 day repeated dose toxicity study was performed with the test substance bromochloromethane. 50% of bromochloromethane in olive oil was administered by stomach tube to several series of white Swiss mice. Three series of mice were given a single dose of 500, 3,000 and 4,500 mg/kg, respectively, and a fourth series was given 3,000 mg/kg on one to ten consecutive days. The control group received olive oil only. Several representative mice from each series were killed for histologic examination and some of the mice that died were also examined. Fatty degeneration of the liver and kidney, as well as focal necrosis and hydropic degeneration of the liver was observed in the 3,000 and 4,500 groups after single oral dose. Changes were most severe after 24 hours and were reversible in mice surviving 48 hours. No effects were noted at 500 mg/kg. In the series of mice given multiple doses of 3000 mg/kg, the lesions were more frequent, severe and prolonged than after a single dose. The oral LD50 in mice was determined to be 4300 mg/kg bw.

Supporting study: An acute oral toxicity test was performed with bromochloromethane. 5000 and 7000 mg/kg of a 50% solution of the test substance in corn oil was administered to groups of 5 male rats. All animals survived the dose of 5000 mg/kg, while all animals died within 24 hours after a dose of 7000 mg/kg. Thus, it can be concluded that the oral LD50 for male rats is > 5000 mg/kg.

Acute toxicity, inhalation:

Key study: A single inhalation and 5 day repeated dose toxicity study was performed with the test substance bromochloromethane. Swiss mice were exposed to bromochloromethane for seven hours on one to five successive days to concentrations ranging from 7 to 17 mg/l. Several mice were killed for histologic study immediately and at intervals following completion of each of the one to five exposures. Marked visceral congestion, fatty degeneration of the liver, the kidney and occasionally of the heart, lipoid depletion of the inner portion of the adrenal cortex, interstitial pneumonitis and opacity of one or both eyes were observed. Less frequent lesions were tubular necrosis and hemoglobin casts in the kidney. It was found that the LC50 concentration was 12 mg/l or 12171.05 mg/m3.

Key study: The purpose of this study was to determine the conditions causing essentially 100% and 0% mortality after inhalation exposure to bromochloromethane. Male and female rats were exposed for 7 hours at 5,000 ppm of the test substance, 1, 1.5, 2, 4 and 6 hours at 10,000 ppm, 0.3, 0.4, 0.5, 1, 1.5 and 2 hours at 20,000 ppm, 0.1, 0.2, 0.3, 0.4 and 0.6 hours at 40,000 ppm and at 80,000 ppm of the test substance for 0.1 and 0.2 hours. The animals were observed during exposure and until death occurred or until consciousness was regained. The rats were weighed before exposure, the day following exposure and at intervals for two weeks thereafter or until it was apparent that all animals had recovered and were gaining weight normally. No mortality was observed in the 5,000 ppm exposed group. The minimum exposures causing essentially mortality were 2 hours at 10,000 ppm, 0.5 hours at 20,000 ppm, 0.2 hours at ≥ 40,000 ppm. Drowsiness was apparent in rats exposed for 7.0 hours to 5,000 ppm. Rats exposed to 10,000 ppm were very drowsy after 1.5 hours and unconscious after two hours. Rats exposed to 20,000 ppm were unconscious at the end of 15 minutes exposure and those exposed to 40,000 ppm were unconscious after six minutes of exposure. With few exceptions, rats that recovered consciousness quickly regained any loss of body weight. On the basis of these results, the inhalative LC0 for bromochloromethane was determined to be 5,000 ppm (or 26458.81 mg/m3) after 7-hour exposure period and 10,000 ppm (or 52917.63 mg/m3) was determined to be the LC100 for bromochloromethane after 6 hours of inhalation exposure.

Acute toxicity, dermal:

Supporting study: In the present acute dermal toxicity study conducted with the test substance bromochloromethane, belly hair was clipped from the rabbits and a single application of the test substance was applied using a modified Draize technique. Four out of four rabbits survived a dose of 5000 mg/kg, and only a slight loss of body weight occurred over the observation period. Clinical observations included a burn and denaturation of the skin with occlusive application. On the basis of these results, the dermal LD50 of bromochloromethane is determined to be > 5000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
The key study was chosen.

Justification for selection of acute toxicity – inhalation endpoint
The study with lowest LC50 was chosen.

Justification for selection of acute toxicity – dermal endpoint
Only one study is available. The dermal LD50 of bromochloromethane is determined to be > 5000 mg/kg bw.

Justification for classification or non-classification

Based on available data, bromochloromethane is not classified for acute toxicity according to CLP Regulation (EC) no 1272/2008.