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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:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study was conducted in complaince with OECD GLP (1982) regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Perfluorpropylvinylether (PPVE), MTDID 16437
- Substance type: pure active substance
- Physical state: liquid
- Analytical purity: 98.5%
- Storage condition of test material: At room temperature in the dark under nitrogen
- Other: Flush container with nitrogen after handling
Specific details on test material used for the study:
- Name of test material (as cited in study report): Perfluoropropyl vinyl ether
- Substance type: Mono-constituent
- Physical state: Liquid
- Analytical purity: 88%
- Purity test date: No data
- Lot/batch No.: No data
- Expiration date of the lot/batch: No data
- Storage condition of test material: At room temperature in the original container

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited
- Age at study initiation: 6-8 weeks
- Weight at study initiation: All rats were approximately 200 grams
- Fasting period before study: None
- Housing: 5 animals of the same sex per cage in stainless steel sheet and wire mesh cages (35 cm x 53 cm x 25 cm)
- Diet (e.g. ad libitum): SDS RM1 ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-25
- Humidity (%): 20-62
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 July 1993 To: 05 November 1993

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 120 Liter whole body exposure chambers.
- Exposure chamber volume: 120 Liters
- Method of holding animals in test chamber: Animals separated by wire partitions inside chamber
- Source and rate of air: Clean, dried air at 25 liters/minute
- Method of conditioning air: Compressed air supply to the test atmosphere generator was dried, flitered and oil-free.
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: Five air samples were taken from the chamber during each exposure and analyzed via GLC
- Samples taken from breathing zone: No
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
0 (Negative control), 12.4, 21.8, 40.8, 58.7 mg/L.
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed continuously during exposure and at least twice daily throughout the study. Clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5, and 1.0 hours and then at hourly intervals during the exposure. During the observation period the clinical signs were recorded once in the morning and then as necessary following a later check for clinical signs.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 58.7 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
In the 12.4 mg/L group, one (1/5) female rat died on Day 1 of the observation period. In the 21.8 mg/L group, one male (1/5) and one female (1/5) rat died after post exposure clinical signs were recorded on Day 0. One male (1/5) and two female (2/5) died on Day 2 of the observation period. In the 40.8 mg/L group, one male (1/5) rat died after the post exposure clinical signs were recorded on Day 0. One male (1/5) rat died on Day 1 and one female (1/5) died on Day 2 of the observation period.

Following review by the sponsor of the procedures for cleaning of the sample cylinders for the 2 consignments of the test compound, the sponsor considers that the first consignment may have been contaminated by hydrofluoric acid formed following incomplete drying of the cylinder used. The second consignment was used for the exposure at 58.7 mg/L in air.

At 58.7 mg/L, no mortality was observed during the study period.
Clinical signs:
other: During exposure, restlessness and increased resperation rate were observed in the rats exposed to 12.4 mg/L. No clinical signs were observed during exposure in the 21.8 mg/L group. Increased respiration, piloerection and partial eye closing was observed i
Body weight:
The rate of body weight gain for all test groups was reduced for up to 2 days following exposure. Subsequently, the rate of bodyweight gain for rats that survived exposure to the test article was similar to that of the control rats.
Gross pathology:
Macroscopic abnormalities observed in rats exposed at 12.4, 21.8, and 40.8 mg/L were slight to severe congenstion and dark subpleural foci in the lungs, wet fur, red staining or clear discharge around the snout and white frothy fluid in the trachea. With the exception of pale, raised areas in the lungs of one female, there were no macroscopic abnormalities in the rats exposed to 58.7 mg/L test article.
Other findings:
- Organ weights: The lung weight to body weight ratios were higher than control values in rats that died as a result of exposure to the test article. The ratios for the rats that survived exposure to the test article were similar to values for controls.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the study, the 4 -hour acute inhalation LC50 of the test article is greater than 58.7 mg/L, vapor.
Executive summary:

The 4-hour acute inhalation lethality of the test article was determined in Sprague-Dawley rats. The study was conducted in compliance with GLP (1982) regulations. The test method was based on OECD Guideline 403. Rats (5/sex/group) were exposed to 0 (negative control), 12.4, 21.8, 40.8, or 58.7 mg/L test article for a single, whole body 4-hour exposure. Rats were observed continuously during exposure and at least twice daily throughout the study. Clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5, and 1.0 hours and then at hourly intervals during the exposure. During the recovery period clinical signs were recorded once in the morning and then as necessary following a later check for clinical signs of toxicity. All rats were weighed daily until the end of the recovery period (Day 14). A gross necropsy was performed on all surviving rats on Day 14 following exposure.

Following review by the sponsor of the procedures for cleaning of the sample cylinders for the 2 consignments of the test compound, the sponsor considers that the first consignment, which was used for the 12.4, 21.8 and 40.8 mg/L exposures, may have been contaminated with hydrofluoric acid formed following incomplete drying of the cylinder used. The second consignment was used for the exposure at 58.7 mg/L test article.

No mortality was observed in animals exposed to 58.7 mg/L; clinical signs of toxicity observed during the exposure included fast respiration and piloerection which had resolved by one day post-exposure. Food consumption was normal and water consumption was slightly above that of the control animals during the recovery period. At necropsy, no abnormalities were observed in rats exposed to 58.7 mg/L except for one female that demonstrated pale raised areas in the lungs.

During the 40.8 mg/L exposure, partially closed eyes, fast respiration and restless behavior were observed which lasted for up to 4 days post-exposure. Three males and 1 female (total mortality 4/10) died within 2 days of the exposure. Food and water consumption was reduced for up to 3 days following the 40.8 mg/L exposure and animals demonstrated body weight losses for 2 days post-exposure. At necropsy, slight to severe congestion and dark subpleural foci in the lungs, wet fur, red or clear discharge from the nose and white frothy fluid were observed. No adverse clinical signs of toxicity were noted during the 21.8 mg/L exposure; however, exaggerated and fast respiration, immobility convulsions in response to sound were noted for up to 3 days post-exposure. Two male and 3 females were found dead (5/10 total mortality) between days 1 and 2 post-exposure. Food and water consumption was reduced for up to 3 days following the 21.8 mg/L exposure and animals demonstrated body weight losses for 2 days post-exposure. At necropsy, slight to sever congestion and dark subpleural foci in the lungs, wet fur, red or clear discharge from the nose and white frothy fluid were observed. Restless behavior and fast respiration were noted during the 12.4 mg/L exposure and exaggerated respiration was noted for up to 3 days post-exposure. One female was found dead (1/10 total mortality) one day post-exposure. Food and water consumption was reduced for up to 3 days following the 12.4 mg/L exposure and animals demonstrated body weight losses for 2 days post-exposure. At necropsy, slight to severe congestion and dark subpleural foci in the lungs, wet fur, red or clear discharge from the nose and white frothy fluid were observed.

Therefore, based on the results of this study, the 4-hour acute inhalation LC50 of the test article is greater than 58.7 mg/L, vapor.