3,3,4,4,4-pentafluorobut-1-ene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25th October 2016 - 19th January 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

yes

Remarks:

The deviations were considered to have not affected the integrity or validity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.52 (Acute Inhalation Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

The deviations were considered to have not affected the integrity or validity of the study.

Principles of method if other than guideline:

The study was designed to assess the acute inhalation toxicity of the test substance (3, 3, 4, 4, 4-pentafluorobut-1-ene (CAS No. 374-27-6)) in the Wistar strain rat.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,3,4,4,4-pentafluorobut-1-ene

EC Number:

206-775-3

EC Name:

3,3,4,4,4-pentafluorobut-1-ene

Cas Number:

374-27-6

Molecular formula:

C4H3F5

IUPAC Name:

3,3,4,4,4-pentafluorobut-1-ene

Test material form:

gas

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Test material: 3,3,4,4,4-pentafluorobut-1-ene
- CAS number: 374-27-6
- Physical state: colourless gas
- Batch No.of test material: 31101
- Expiration date of the lot/batch: 26 November 2017
- Purity: 99.753%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 200-350g
- Fasting period before study: not specified
- Housing: The animals were housed in groups of up to three by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes.
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet (supplied by Envigo RMS (UK) Limited
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness (controlled by a time switch)

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Test chamber
- Exposure chamber volume: Approximately 30 litres (dimensions: 28cm diameter x 50cm high)
- Method of holding animals in test chamber: Each rat was individually held in a tapered polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring.
- Test animals: Following an appropriate equilibration period, a single group of 6 rats (3 males and 3 females) was exposed to an atmosphere of the test substance for a period of 4 hours
- Target concentration of test substance: 20000 ppm was used for the exposure
- Source and rate of air: The test substance was ducted directly from the gas canister via a flow meter into the test chamber, which provided a continuous supply of test substance. Compressed air was supplied by means of an oil-free compressor.
- Method of conditioning air: Compressed air was passed through a water trap and respiratory quality filters before it was introduced to the exposure chamber.
- Temperature, humidity, pressure in air chamber: Temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds., UK, located in a vacant port in the breathing zone of animals. It was recorded every 30 minutes throughout the 4-hour exposure period.
- Oxygen levels: measured by an electronic oxygen analyser (Servomex (UK) Ltd, Crowborough, East Sussex) located in a port in the breathing zone of the animals during the 4-hour exposure period. The test atmosphere was generated to contain at least 19% oxygen.

TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: yes
- the chamber atmosphere was sampled nine times during the exposure period
- 5 mL samples of the generated atmosphere were removed using a gas-tight syringe and were transferred to 20 mL head-space vials for gas chromatographic (GC) analysis of the test item concentrations.
- The nominal chamber concentration was calculated by dividing the mass of the test substance disseminated into the chamber by the total volume of air that flowed through the chamber during exposure, the resulting value was then converted to mg/L.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

A target concentration of 20000 ppm was used for the exposure.

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy
1. Clinical signs
- All animals were observed for clinical signs at: (1) hourly intervals during exposure; (2) immediately on removal from the restraining tubes at the end of exposure; (3) 1 hour after termination of expsoure; (4) once daily for 14 days.
- Any evidence of overt toxicity was recorded at each observation.

2. Body weight
- Individual body weights were recorded on arrival, prior to treatment on the day of exposure (Day 0) and on Days 1, 3, 7 and 14. 3.

3. Necropsy
- At the end of the 14 day observation period, the animals were killed by intravenous overdose of sodium pentobarbitone.
- All animals were subjected to a full external and internal examination and any macroscopic abnormalities were recorded.
- The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.

Statistics:

Not specified

Results and discussion

Preliminary study:

N/A

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 24 533 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not measured/tested

Remarks:

GHS: unclassified

Mortality:

There were no deaths.

Clinical signs:

other: Signs of hunched posture and pilo-erection are commonly seen in animals for short period on removal from the chamber following 4-Hour inhalation studies. Wet fur is commonly reported both during and for a short period after exposure. - these observations

Body weight:

- 2 males and 1 female showed body weight loss or no body weight gains on the first day post-exposure.
- Body weight gains were noted for all male animals during the remainder of the recovery period.
- Females showed further body weight loss or no body weight gains from Day 1-3 post-exposure
- 1 female showed a body weight loss from Days 3-7 post-exposure and a further female exhibited body weight loss during the final week of the recovery period.

Gross pathology:

No macroscopic abnormalities detected amongst animals at necropsy.

Other findings:

N/A

Any other information on results incl. tables

Exposure chamber concentrations

- The mean achieved concentration was 123% of target and no deaths occurred, no further levels were required.

- The chamber flow rate was maintained at 29L/min providing 58 air changes per hour.

- The theoretical chamber equilibration time (T99) was 5 minutes - test atmospheres were generated for a total of 6 minutes prior to animal insertion to ensure the target test substance concentration was being achieved.

Applicant's summary and conclusion

Conclusions:

This study was an investigation into the acute inhalation toxicity of the test substance, 3, 3, 4, 4, 4-pentafluorobut-1-ene in male and female Wistar rats. There were no deaths at a mean achieved atmosphere concentration of 24533 ppm for 4 hours, therefore the acute inhalation median lethal concentration (4-hour LC50) of the test substance in the Wistar strain rat was considered to be greater than 24533 ppm and is unclassified according to the Globally Harmonised Classification System.

Executive summary:

This study was an investigation into the acute inhalation toxicity of the test substance, 3, 3, 4, 4, 4-pentafluorobut-1-ene in male and female Wistar rats. The study was conducted in accordance with OECD 436 and EU Method B.52 guidelines. There were some deviations from the guidelines, but these were considered not to affect the integrity or validity of the study.

Six Wistar rats (three males and three females) were exposed to a gaseous atmosphere of the test item. The animals were exposed for 4 -hours using a nose-only exposure system, followed by a fourteen-day observation period. A target concentration of 20000 ppm was used for the exposure. The mean achieved concentration was 123% and since there were no deaths, no further levels were required for testing. The exposure chamber was sample and the nominal chamber concentration was calculated, which was 78% of the actual mean achieved atmosphere concentration, which implies that generating the test substance as a gas was straightforward. A mean achieved atmosphere concentration of 24533 ppm for 4 hours was achieved.

In terms of observations, common abnormalities noted during the study included decreased respiratory rate, increased respiratory rate, hunched posture and wet fur. The animals appeared to recover and return to normal on Day 1 post-exposure. 2 males and 1 female showed body weight loss or no body weight gains on the first day post-exposure, whereas body weight gains were observed for all males during the remainder of the recovery period. Also, all females showed further body weight loss or no body weight gains from Days 1 -3 post-exposure. 1 female showed a body weight loss from Days 3 -7 post-exposure and a further female exhibited body weight loss during the final week of the recovery period. There were no macroscopic abnormalities found during necropsy.

The acute inhalation median lethal concentration (4-hour LC50) of the test substance in the Wistar strain rat was considered to be greater than 24533 ppm and is unclassified according to the Globally Harmonised Classification System.