1,1,2,2,3,3,4-heptafluorocyclopentane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1997-04-30 to 1997-06-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

430-710-1

EC Name:

-

Cas Number:

15290-77-4

Molecular formula:

C5H3F7

IUPAC Name:

1,1,2,2,3,3,4-heptafluorocyclopentane

Specific details on test material used for the study:

Lot No.: 9703-1, 9705-2A
Purity: >97%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Manston Road, Margate, Kent, England
- Age at study initiation: approximately 8 weeks and 9 weeks old for males and females respectively
- Weight at study initiation:
- Fasting period before study:
- Housing: housed by sex in groups of 5 in the holding cages (size 35 cm x 53 cm x 25 cm height) which were made of stainless steel sheet and wire mesh and were suspended on a movable rack.
- Diet: SDS rat and mouse diet (RM 1) , ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Photoperiod (hrs dark / hrs light): 12 hurs light between 8 am and 8 pm daily

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

- Atmosphere generator:
The atmosphere generator produced and maintained an atmosphere containing vapour by evaporation of the test substance from a fitted glass disc with a countercurrent of air. All parts of the generator in contact with the test substance were made of glass. The test substance was delivered to the generator from a syringe driven at a constant rate by a syringe pump. The air supplied to the generator was dried, filtered and oil free.
- Exposure chambers:
The snout-only exposure chambers were of cylindrical form and made of aluminium alloy. The chambers used for Groups 1, 2, 3 and 5 (30 cm diameter and 45 cm height) had an enclosed volume of approximately 30 litres. The chamber used for Group 4 (10 cm diameter and 65 cm height) had an enclosed volume of approximately 5 litres. The rats were held for exposure in moulded polycarbonate tubes which were attached at evenly spaced ports in the cylindrical section of the chamber. The tubes were tapered at one end t allow the snout only to project into the chamber. The other end was closed by insertion of an expanded plastic bung. A push rod passed through the centre of the bung and was adjusted to maintain the position of a rat during exposure. The test atmosphere entered the chamber through a port at the top centre of the chamber and was extracted at the base centre below the level of the rats. Each chamber was installed in a large fume cupboard exhausting through an absolute filter.
- Test procedure:
A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 30 litres per minute (initial exposure) measured at the generator outlet tube. The air supply to the generator was heated by a water bath maintained at between 52 to 58°C. An in-line flow meter was used to monitor air flow throughout the exposure.
A syringe filled with test item was fitted to the syringe pump and connected to the generator with PTFE tubing. The syringe was surrounded by a water jacket maintained at between 52 to 58°C. The generator was situated in a water bath maintained at between 63 to 66°C. The flow rate selected for the first exposure was expected to give a vapour concentration of approximately 5000 ppm.
The rats to be exposed were placed into restraining tubes. The tubes were attached to the ports in the mid section of the chamber.
After 4 hours, the supply of test substance was discontinued and the exposure chamber was allowed to clear before the rats were removed for examination.
This procedure was repeated for Groups 3 and 5 using air flows of 10 litres per minute and 3 litres per minute for Group 4. Flow rates selected for Groups 3, 4 and 5 were expected to give vapour concentrations of 10000, 20000 and 12000 ppm respectively. Equilibrate tissues (T90) at 10 litres per minute were 6.9 and 3.8 minutes respectively.
- Chamber atmosphere analyses:
Between 7 and 12 air samples (variable due to early termination of one exposure and repeat samples removed during other exposures) were taken from the chambers during each exposure and the concentration of test item in the chamber air was determined by chemical analysis.
Each chamber air sample was withdrawn into a gas tight syringe.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Groups 1, 2, 3, 4 and 5: 5245, 9422, 23739, 12055 ppm

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Clinical signs: During the observation period, the clinical signs were recorded immediately post exposure, at 1 and 2 hours post-exposure and thereafter once in the morning and then as necessary following a later check for clinical signs.
- Bodyweight: weighed daily from the day of delivery up to and including the day of sacrifice/death.
- Food and water consumption: measured daily from the day of arrival to sacrifice/death.
- Necropsy of survivors performed: yes, At the end of the 14-day observation period, surviving rats were killed by intraperitoneal injection of pentobarbitone sodium and exsanguinated when clinically dead. All rats were subjected to a detailed macroscopic examination.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

14 213 ppm

Based on:

test mat.

95% CL:

> 11 093.2 - < 17 332.4

Exp. duration:

4 h

Mortality:

AII deaths (10/10) in rats exposed at 23739 ppm occurred during the last 2 hours of the start of exposure.
Deaths (4/10) in rats exposed at 12055 ppm occurred during the last 2 minutes of the 4 hour exposure.

Clinical signs:

other: - During the exposure: Signs recorded during exposure were severely restricted to those most obvious under the conditions of tube restraint. Exaggerated respiratory movements and a reduced rate of respiration were seen in rats exposed to test item at all

Body weight:

There was a slight reduction in the rate of bodyweight gain for rat exposed to test item at 5245 ppm and a moderate reduction in the rate of bodyweight gain for male rats exposed at 12055 ppm for 1 day. Otherwise the rate of bodyweight gain for surviving test rats was similar to those of the controls.

Gross pathology:

Dark foci were seen on the lungs of one male rat exposed at 5245 ppm.
Decedent rats exposed at 12055 or 23739 ppm were noted to have congested lungs (minimal/moderate/severe). One decedent rat exposed at 23739 ppm had dark foci on the right anterior and right azygous lobes. No other macroscopic abnormalities detected.

Other findings:

- Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15.
- Food consumption:
Food consumption for rats surviving exposure to test item was reduced for 1 day only. The reduction was related to treatment with test item and was more pronounced in males.
- Water consumption：
Water consumption for male rats exposure to test item at 120555 ppm was reduced for 1 day only. Otherwise water consumption for test rats was similar to that of the control rats.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LC50 (4 hour) for test item is estimated at 14213 ppm (124401.8 mg/m3) in air for males and females combined.

Executive summary:

The acute inhalation toxicity of test item was assessed by exposing 4 groups of rats, for a period of 4 hours, to an atmosphere produced from the test substance at concentrations of 5245, 9422, 23739 or 12055 ppm of air. A further group, acting as a control was exposed to clean air only. The study design was in compliance with OECD 403.

Deaths occurred during exposure in rats exposed at 12055 (4/10, during the last 2 minutes of the 4 hour exposure) and 23739 ppm (10/10, during the last 2 hours of the start of exposure).

Signs recorded during exposure were severely restricted to the conditions of tube restraint. Exaggerated respiratory movements and a reduced rate of respiration were seen in rats exposed to test item at all levels. Shallow breathing (initially) and deep breathing were seen in rats exposed at 9422 ppm.

During the observation period, staggering and half closed eyes were seen in rats exposed at 5245 and 12055 ppm. Slow respiration and unconsciousness (no response to the pinch reflex) were noted in rats exposed at 9422 and 12055 ppm. Additional signs seen in rats exposed at 12055 ppm were whole body hypothermia, pilo erection and a hunched posture. Lethargy (slight) was seen in all rats following exposure to test item at 9422 ppm. All surviving rats were normal in appearance and behaviour by Day 1 of the observation period. Fur soiled with excreta was seen in test and control rats during and immediately following exposure. This sign is attributed to the method of restraint.

There was a slight reduction in the rate of bodyweight gain for rat exposed to test item at 5245 ppm and a moderate reduction in the rate of bodyweight gain for male rats exposed at 12055 ppm for 1 day. Otherwise the rate of bodyweight gain for surviving test rats was similar to those of the controls.

Dark foci were seen on the lungs of one male rat exposed at 5245 ppm. Decedent rats exposed at 12055 or 23739 ppm were noted to have congested lungs (minimal/moderate/severe). One decedent rat exposed at 23739 ppm had dark foci on the right anterior and right azygous lobes. No other macroscopic abnormalities detected.

 

The LC50 (4 hour) for test item is estimated at 14213 ppm (124401.8 mg/m3) in air for males and females combined.