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

Endpoint summary

Description of key information

Oral:

This study was performed to assess the acute oral toxicity of test item to the rat based on EC method B.1.

The acute lethal oral dose (LC50) to rats of test item was demonstrated to be greater than 2000 mg/kg bodyweight.

Inhalation:

The acute inhalation toxicity of test item was assessed in compliance with OECD 403. The LC50 (4 hour) for test item is estimated at 14213 ppm (124401.8 mg/m3) in air for males and females combined.

Dermal:

A study was performed to assess the acute dermal toxicity of test item to the rat following EC B.3. The acute lethal dermal dose (LC50) to rats of test item was demonstrated to be greater than 2000 mg/kg bodyweight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1997-07-17 to 1997-07-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

OJ No. L383A, 29.12.92

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Batch No.: 9706-1A
Purity: 98.65

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: selected from a stock supply of healthy male and female CD rats of Sprague-Dawley origin (Hsd: Sprague-Dawley(CD)) which were obtained from Harlan UK Ltd, Bicester, Oxon, England.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: four to seven weeks
- Weight at study initiation: 92 to 115 g
- Fasting period before study: overnight
- Housing: housed in groups of up to five rats of the same sex in metal cages with wire mesh floors
- Diet: standard laboratory rodent diet (SpeciaI Diet Services RMl(E) SQC expanded pelIet), ad libitum
- Water: ad libitum
- Acclimation period: seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 245-6330-70
- Air changes (per hr): > 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours)

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item was administered as supplied, at a dose volume of 1.226 mL/kg bodyweight.

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5 Males
5 Females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes, All animals were killed on Day 15 by carbon dioxide asphyxiation. All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.
- Examinations performed:
- Mortality: Cages of rats were checked at least twice daily for any mortalities.
- Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
- Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Males: 0/5
Females: 0/5

Clinical signs:

Piloerection was observed in all rats within 22 minutes of dosing. There were no other clinical signs and recovery was complete in all animals by Day 2.

Body weight:

All rats were considered to have achieved satisfactory bodyweight gains throughout the study.

Gross pathology:

No macro-pathological abnormality revealed at necropsy.

Interpretation of results:

other: Not classified

Conclusions:

The acute oral LD50 of the test substance in rats is > 2,000 mg/kg bw.

Executive summary:

This study was performed to assess the acute oral toxicity of test item to the rat based on EC method B.1.

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, as supplied, administered at a dose level of 2000 mg/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths. Clinical signs of reaction to treatment were confined to piloerection seen in all rats, recovery was complete by Day 2.

All rats were considered to have achieved satisfactory bodyweight gains throughout the study.

No abnormalities were revealed at the macroscopic examination of animals killed at study termination on Day 15.

The acute lethal oral dose (LC50) to rats of test item was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

1 (reliable without restriction)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

124 401.8 mg/m³

Quality of whole database:

1 (reliable without restriction)

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1997-09-03 to 1997-09-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

OJ No. L383A, 29.12.92

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Batch No.: 9705-2A
Purity: 98.18%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: selected from a stock supply of healthy male and female CD rats of Sprague-Dawley origin (Hsd: Sprague-Dawley(CD)) which were obtained from Harlan UK Ltd, Bicester, Oxon, England.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately seven to eight weeks
- Weight at study initiation: 200 to 247 g
- Fasting period before study:
- Housing: Housed individually in metal cages with wire mesh floors
- Diet: standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet), ad libitum
- Water: ad libitum
- Acclimation period: at least six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 23
- Humidity (%): 38-65
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 50 mm x 50 mm
- Type of wrap if used: The treatment area was covered with porous gauze held in place with a non irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of exposure period the dressings was carefully removed and the treated area of skin was washed with warm water (30 to 40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 1.231 mL/kg bodyweight

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

five males and five females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Mortality: at least twice daily
- Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1, once in the morning and again at the end of experimental day for subsequent days (with the exception of Day 15 - morning only).
- Dermal responses: assessed daily
- Bodyweight: recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes, All animals were killed on Day 15 by cervical dislocation and subjected to a macroscopic exanimation which consisted of opening the abdominal and thoracic cavities.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

no signs of systemic reaction to treatment observed

Body weight:

A slightly low bodyweight gain was recorded for one female on Day 8. All other rats were considered to have achieved satisfactory bodyweight gains throughout the study.

Gross pathology:

No abnormalities were recorded

Other findings:

- Dermal Reactions:
Transient slight dermal irritation (Grade 1 erythema only) was seen in two animals on removal of the dressings, and resolving in both instances by Day 4. In addition desquamation (characterised by localised spots/scabbing) was observed in one of these rats from Day 7 through Day 11. No dermal response to treatment was recorded for the remaining eight rats throughout the study.

Interpretation of results:

other: Not classified

Conclusions:

The acute lethal dermal dose (LC50) to rats of test item was demonstrated to be greater than 2000 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute dermal toxicity of test item to the rat following ECB.3.

A group of ten rats (five males and five females) received a single dose by topical application of the test substance administered, as supplied, at a dose level of 2000 mg/kg bodyweight. All animals were kill and examined macroscopically on Day 15, the end of the observation period.

There were no deaths and no signs of systemic reaction to treatment observed throughout the study.

Transient slight dermal irritation (Grade 1 erythema only) was seen in two animals on removal of the dressings, and resolving in both instances by Day 4. In addition desquamation (characterised by localised spots/scabbing) was observed in one of these rats from Day 7 through Day 11. No dermal response to treatment was recorded for the remaining eight rats throughout the study.

A slightly low bodyweight gain was recorded for one female on Day 8. All other rats were considered to have achieved satisfactory bodyweight gains throughout the study.

No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal dermal dose (LC50) to rats of test item was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

1 (reliable without restriction)

Justification for classification or non-classification

Acute toxicity:

Oral:

Acute oral toxicity test, EC B.1: LD50: > 2000 mg/kg body weight

Inhalation:

Acute inhalation toxicity test, OECD 403, LC50: 14213 ppm

Dermal:

Acute dermal test, EC B.3: LD50 >2000 mg/kg.

Therefore in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1, this substance should be classified as Category 4 for acute inhalation and not classified for acute oral and dermal toxicity.

 

Specific target organ toxicity-single exposure:

Oral:

Acute oral toxicity test,EC B.1:

Mortality: no deaths

Clinical observations: confined to piloerection seen in all rats, recovery was complete by Day 2.

Necropsy: No abnormalities

Inhalation:

Acute inhalation toxicity test, OECD 403:

Mortality: 4/10 died at 12055 ppm and 10/10 died at 23739 ppm

Clinical observations:

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.

Necropsy: 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.

 

Acute dermal test, EC B.3:

Mortality: no deaths

Clinical observations: no signs of systemic reaction to treatment observed

Necropsy: No abnormalities were recorded

 

In accordance with Regulation (EC) No. 1272/2008 section 3.8.2.1.7., the effects observed are not considered as adverse effects that support classification, therefore this substance should be not classified.