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Toxicological information

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:
Unnamed
Year:
1948

Materials and methods

Principles of method if other than guideline:
Single inhalation and 5-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:
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.

Results and discussion

Effect levels
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.

Applicant's summary and conclusion

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).