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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment. Study was conducted under non-standard guideline (Class B Poison Test).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971
Report Date:
1971

Materials and methods

Principles of method if other than guideline:
Six young adult male rats per dose level were exposed whole body to 0.12, 0.38, 0.60, 0.66, 2.31 mg/L of the test substance for four hours. Rats were sacrificed and necropsied at one, two, and six days after exposure to 0.12 mg/L and 14 days after exposure to 0.6 mg/L.
GLP compliance:
not specified
Test type:
other: Class B Poison Test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 99.9%

Test animals

Species:
rat
Strain:
other: ChR-CD
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 250-280 grams.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: air; (nitrogen was used to pass chemical into exposure chamber where it was then mixed with oxygen and diluting air to give an 20% O2 (v/v) concentration)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Bell jar.
- Exposure chamber volume: 16 litre.
- Method of holding animals in test chamber: Whole body.
- System of generating particulates/aerosols: The test substance was put in a three-neck glass flack in a heated (100°C) mineral oil bath. Aerosols of the compound were prepared from this molten test substance by a stainless steel nebulizer submerged into the melt. Nitrogen was passed through the nebulizer to carry the vapours into a 16-liter bell-jar containing six young adult male rats. Oxygen and diluting air were added to the stream prior to entering the exposure changer to give 20% oxygen (v/v) in the chamber atmosphere and to adjust the concentration.

TEST ATMOSPHERE
- Brief description of analytical method used: Concentration determined at least three times during each 4 hour exposure by drawing a known volume of chamber atmosphere through two impingers in series. n-Heptane was the scrubbing solvent. The solution was analyzed by ultraviolet light absorption at 254mµ.
- Samples taken from breathing zone: Yes.

VEHICLE
- Composition of vehicle (if applicable): Nitrogen was used to pass chemical into exposure chamber where it was then mixed with oxygen and diluting air to give an 20% O2 (v/v) concentration.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Concentration determined at least 3 times during each 4 hour exposure by drawing a known volume of chamber atmosphere through 2 impingers in series. n-Heptane was the scrubbing solvent. The solution was analyzed by ultraviolet light absorption at 254mµ.
Duration of exposure:
4 h
Concentrations:
0.12, 0.38, 0.60, 0.66, 2.31 mg/L.
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: Up to 14 days.
- Frequency of observations and weighing: Weight measured daily.
- Necropsy of survivors performed: Yes. Rats were sacrificed at one, two and six days after exposure to 0.12mg/l and 14 days after exposure to 0.6mg/L. Tissues examined included: lungs, liver, kidney, brain, lymph nodes, spleen, testes, gastrointestinal tract, thyroid, adrenal, skin, bone marrow, pancreas, epidedymis, thymus, and eye.
- Other examinations performed: Clinical signs during exposure.
Statistics:
Statistical analysis by method of Litchfield, J. T., Jr. and F. Wilcoxon, J. Pharmacol. and Expt'l. Therap., 96:99 (1949).

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
0.7 mg/L air
95% CL:
0.46 - 1.06
Exp. duration:
4 h
Mortality:
0/6 at 0.12 mg/L; 1/6 at 0.38 mgL; 2/6 at 0.60 mg/L; 3/6 at 0.66 mg/L; and 6/6 at 2.31 mg/L.
Clinical signs:
other: 0.12mg/L- During exposure: Slight difficulty breathing, otherwise normal 0.38mg/L- During exposure: Heavy breathing, occasional face pawing, gasping. One death at 2.5 hours 0.60mg/L- During exposure: Lacrimation, face pawing, heavy breathing and gasping.
Body weight:
0.12mg/L- Down to 82% of their initial body weight on the 1st day.
0.38mg/L- Down to 76% of initial body weight on the 2nd day post-exposure, normal recovery thereafter.
0.60mg/L- Down to 83% of initial body weight on the 1st day of recovery, normal recovery thereafter.
0.66mg/L- Down to 82% of initial body weight 1st day post-exposure. All but one started to recover 2nd day post-exposure. The one was down to 75% of initial body weight on the 5th day of recovery and gained normally thereafter.
Gross pathology:
Rats were sacrificed at one, two, and six days after exposure to 0.12 mg/L and 14 days after exposure to 0.6 mg/L. The rat which died during exposure to 0.38 mg/L and one of those which died during exposure to 2.31 mg/L were also necropsied for gross and histopathologic examination. Gross examination at necropsy revealed severe pulmonary oedema and congestion.
Slight pulmonary congestion and oedema were still noted in rats sacrificed one day post-exposure. They also showed acute necrotic tracheobronchitis, hyperplasia of granular alveolar cells and depletion of hepatic cell glycogen.
The rats sacrificed two days post-exposure showed no evidence of pulmonary oedema, but glycogen depletion of the hepatic cells was still evident.
Rats sacrificed at six and 14 days post-exposure exhibited regeneration of the tracheobronchial epithelium and had normal amounts of glycogen in the hepatic cells.
Depletion of glycogen in the hepatic cells was considered a transient change due to stress and anorexia following exposure and reflected the nutritional condition of the test rats.

Any other information on results incl. tables

Decreased body weight days 1-5 days post exposure and normal thereafter. Slight pulmonary congestion and oedema; acute necrotic tracheobronchitis, hyperplasia of granular alveolar cells; and depletion of hepatic cell glycogen were observed one day post exposure. At two days post exposure, no evidence of pulmonary oedema was observed, but glycogen depletion of the hepatic cells was still evident. At 6 and 14 days post exposure regeneration of the tracheobronchial epithelium and normal amount of glycogen in the hepatic cells were observed. Depletion of glycogen in the hepatic cells was considered a transient change due to stress and anorexia following exposure and reflected the nutritional condition of the test rats.

Applicant's summary and conclusion

Interpretation of results:
highly toxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
LC50 = 0.7 mg/L
Executive summary:

Male rats were exposed to the test substance for 4 hours by inhalation at concentrations of 0.12, 0.38, 0.60, 0.66 and 2.31 mg/L. The LC50 was 0.7 mg/L. Decreased body weight was observed on days 1-5 days post exposure and was normal thereafter. Slight pulmonary congestion and edema; acute necrotic tracheobronchitis, hyperplasia of granular alveolar cells; and depletion of hepatic cell glycogen were observed one day post exposure. At two days post exposure no evidence of pulmonary edema was observed but glycogen depletion of the hepatic cells was still evident. At 6 and 14 days post exposure regeneration of the tracheobronchial epithelium and normal amount of glycogen in the hepatic cells were observed. Depletion of glycogen in the hepatic cells was considered a transient change due to stress and anorexia following exposure and reflected the nutritional condition of the test rats.