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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is an acceptable, well-documented, GLP-compliant study report equivalent or similar to OECD Guideline 403.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MCP 992
- Physical state: colorless liquid
- Lot/batch No.: P9H056
- Expiration date of the lot/batch: August, 2005
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Stone Ridge, NY, USA
- Age at study initiation: males: ~9 weeks; females: ~10 weeks
- Weight at study initiation: males: 310-326g; females: 232-246g
- Fasting period before study: not reported
- Housing: individually housed in suspended stainless steel and wire mesh cages with indirect-absorbent paper
below cages.
- Diet (e.g. ad libitum): ad-libitum during non-exposure; PMI Feeds, Inc., Richmond, IN; availability of feed
checked at least once daily for all animals
- Water (e.g. ad libitum): automatic watering system, ad libitum during nonexposure periods.
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 64-72
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12hrs dark/12 hrs light

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and acrylic whole body inhalation exposure chamber
- Exposure chamber volume: 150L
- Method of holding animals in test chamber: not reported
- Source and rate of air: 30L/min
- System of generating particulates/aerosols: Test substance was administered as received: Generated as a liquid droplet aerosol using a Laskin nebulizer. A three-necked flask was filled with the test substance to a level below the top of the nebulizer barrel. Compressed air was supplied to the nebulizer, at a rate sufficient to aerosolise the test substance. The resultant liquid aerosol atmosphere was expelled from the flask through a glass elbow and into the chamber.
- Method of particle size determination: Siera Instruments Model 210 Cascade Impactor
- Temperature, humidity, pressure in air chamber: Temp: 72-74 F; Humidity: 66-74%; monitored continuously and recorded approx. every 30 minutes
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 15.9%, 50.0%, 84.1%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1, 10, and 15 microns
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
analytical: 4800 mg/m^3
nominal: 6694 mg/m^3
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animal population was observed for mortality and obvious signs of toxicity at ~15 minute intervals during the first hour of exposure and once each hour thereafter throughout the exposure. Body weights were recorded prior to exposure and on Days 7 and 14 post-exposure.
- Necropsy of survivors performed: yes
Statistics:
Statistical analyses included the calculations of means and standard deviations for body weight and body weight change by group and sex.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
< 4 800 mg/m³ air (nominal)
Exp. duration:
4 h
Mortality:
One male rat was found dead following the exposure at the afternoon room check (Day 0), three males and one female were found dead on Day 1, and 1 male and 1 female were found dead on Day 2.
Clinical signs:
other: All of the animals were observed with wet and matted fur after the exposure. One male appeared ungroomed on Day 1. The females exhibited signs of irregular respiration, ungroomed appearance, hypothermia, rales, anogenital staining, little sign of stool, r
Body weight:
The three surviving females lost weight from Day 0 to Day 7 but gained weight from Day 7 to Day 14. Two of the three exhibited a slight overall weight gain from Day 0 to Day 14 while one exhibited a slight decrease.
Gross pathology:
Discoloured lungs in most animals found dead. Two of the three surviving females also exhibited discoloured lungs at the terminal sacrifice.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, the LC50 for an aerosol atmosphere of the test material is less than 4800 mg/m^3. Data are insufficient for classification due to concentration limitations.
Executive summary:

Male and female rats were exposed whole body for 4 hours to a mean liquid droplet aerosol concentration of 4800mg/m^3. The mean particle size (MMAD) was ~1 micron. All rats survived the exposure; one male died ~2 hours post-exposure. Three males and 1 female died the next day and 1 male, 1 female died on Day 2. Three females survived the 14 -day observation period. These females lost weight at the Day 7 weighing interval but recovered and gained weight at Day 14. All rats that succumbed displayed discoloured (reddened) lungs at necropsy. Two of the three surviving females also showed discolored lungs at Day 14. Based on the results of this study, the LC50 for an aerosol atmosphere of the test material is less than 4800 mg/m^3. Data are insufficient for classification due to concentration limitations.

This study received a Klimisch score of one and is classified as reliable without restriction because it is an acceptable, well-documented, GLP-compliant study report equivalent or similar to OECD Guideline 403.