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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
Study period:
From Mar. 03, 1982 to Mar. 18, 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): AC-005
- Physical state: Transparent liquid
- Lot/batch No.: S 13926-145-7
- Storage condition of test material: Room temperature out of direct light

Test animals

Species:
guinea pig
Strain:
other: English smooth-haired guinea pigs (Cavia porcellus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hilltop Laboratory Animals, Scottdale, Pennsylvania
- Age at study initiation: 4-5 wK
- Weight at study initiation: 250-300 g
- Housing: Shoebox-type cages
- Diet: Purina Guinea Pig Chow No. 5025, ad libitum
- Water: Tap water, ad libitum

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas exposure chambers
- Exposure chamber volume: 150 L
- Method of holding animals in test chamber: Stainless steel wire mesh compartmentalised cage
- Method: Whole-body
- Measurement: In the exhaust line by means of a ball-type flow meter
- Temperature and relative humidity: Monitored by sensors
- Decontamination of chamber air: Passing the air through an activated charcoal filter
- Airflow rate: 45 L/min


GENERATION OF TEST ATMOSPHERES:

- Aerosols of Test material: Concentric jet glass atomizer supplied with pre- dried air
- Test material was delivered to the atomizer by a syringe pump
- Aerosols: Atomizer generated a liquid aerosol vertically upward into a glass elutriation column 450 mm high and 65 mm in diameter leading upwards through the bottom of the chamber


TEST ATMOSPHERE:
- Chamber particle size distribution was determined by May Cascade Impactor for sample collection and an optical counting and sizing procedure for analysis.
- Particle size distribution: 2.0 -2.6 µM
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 0.1-0.9 µM
INHALATION CHAMBER TEMPERATURE AND RELATIVE HUMIDITY: 23.7- 24.0 °C and 40-45.3 %


CLASS METHOD:
- Rationale for the selection of the starting concentration: Range finding study indicated that the LC50 could be expected to be in the range 0.18 to 0.47 mg/L based on gravimetric concentrations.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
1 h
Remarks on duration:
-
Concentrations:
Analytical chamber concentration: 0 (air control), 0.233, 0.195, 0.355 and 0.457 mg/L
Nominal Concentrations: 0, 0.41, 0.32, 0.51 and 0.72 mg/L
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Twice daily; Body weight: Prior to treatment, and on Days 2, 3, 4, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and organ weights
Statistics:
Litchfield and Wilcoxon method (1949) was used to calculate LC50, 95 percent confidence limits and dose-response curve.

Results and discussion

Preliminary study:
Range finding study indicated that the LC50 could be expected to be in the range 0.18 to 0.47 mg/L based on gravimetric concentrations.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.06 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Reported 1-h LC50 value is 0.24 mg/L (analytical) with a CI 0.19-0.303 mg/L
Mortality:
Generally, mortality occurred within 3 days of exposure except for one male at 0.355 mg/L that died on Day 13 of the study. One male and 2 females (0.195 mg/L), 3 males and 2 females (0.223 mg/L), 5 males and 3 females (0.355 mg/L) and all animals (0.457 mg/L) died during the study.
Clinical signs:
Clinical signs included weakness or lethargy, gasping or rales and discharge from the eyes, nose or mouth during the first 3 days of study.
Body weight:
Body weight loss occurred in both males and females until Day 2 in Groups 1 to 3. For Groups 4 and 5, death occurred from Day 3 onwards, hence body weight loss could not be determined.
Gross pathology:
Lungs presented mild swelling with moderate to severe reddening and rubbery consistency in all groups of treated males and females. Lungs were collapsed in 3 males at 0.195 mg/L and one animal each at 0.233 and 0.355 mg/L.

Any other information on results incl. tables

Table1.Mortalities

Group

Mortalities

mg/L

Males

Females

Total

0.0

0/5

0/5

0/10

0.233

3/5

2/5

5/10

0.195

1/5

2/5

3/10

0.355

5/5

3/5

8/10

0.457

5/5

5/5

10/10

 

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
Under the test conditions, the inhalation LC50 (4h) of the test material in guinea pigs was calculated to be 0.06 mg/L (LC50 (1h) is 0.24 mg/L with a C.I. = 0.190 to 0.303 mg/L).

Executive summary:

A study was conducted to assess the acute inhalation toxicity of the test substance in guinea pigs. The study was run according to a protocol similar to OECD Guideline 403. Groups of five male and five female English smooth-haired guinea pigs were exposed for a single period of 1 h to an aerosol of test substance at analytically measured concentrations ranging between 0.195 and 0.457 mg/L. Mortality was observed in all treated groups from Days 1-3 except one animal, which died on Day 13. Clinical signs included weakness, respiratory distress and ocular, nasal and oral discharge. Body weight losses occurred in all treated groups. Effects on body weight persisted until the end of the study. Marked gross changes in the lungs such as swelling and reddening were observed, particularly in animals that died during the study. Under the study conditions, the inhalation LC50 (4h) of the test substance in guinea pigs was calculated to be 0.06 mg/L (LC50 (1h) is 0.24 mg/L with a C.I. = 0.190 to 0.303 mg/L) (Collins, 1982).