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Toxicological information

Acute Toxicity: oral

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Administrative data

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.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1948

Materials and methods

Principles of method if other than guideline:
Single gavage and 10 day repeated dose toxicity study.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): monochloromonobromomethane

Test animals

Species:
mouse
Strain:
Swiss
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 20 g

Administration / exposure

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.

Results and discussion

Effect levels
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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.