1,1,2,3,3-pentafluoro-3-(heptafluoropropoxy)prop-1-ene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

This was a screening study so 3 males per dose were utilized.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1,2,3,3-pentafluoro-3-(heptafluoropropoxy)prop-1-ene

EC Number:

817-766-4

Cas Number:

91891-42-8

Molecular formula:

C6F12O

IUPAC Name:

1,1,2,3,3-pentafluoro-3-(heptafluoropropoxy)prop-1-ene

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M Company
- Expiration date of the lot/batch: No data
- Purity test date: 19 June, 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None, test material administered as recieved

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/Envigo
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 173-193 g
- Fasting period before study: None
- Housing: All rats were group housed in solid bottom cages prior to the study and throughout the 14-day recovery period.
- Diet (e.g. ad libitum): Harlan Teklad Rat/Mouse 2018 Diet, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6-22.2
- Humidity (%): 30-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 July, 2017 To: 01 August, 2017

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 51 L static test chamber (TSE Systems, GmbH, Bad Hombur, Germany)
- Exposure chamber volume: 51 L
- Method of holding animals in test chamber: None, whole body exposure
- Source and rate of air: 2.9 LPM
- Method of conditioning air: No data
- System of generating particulates/aerosols: None, vapor
- Method of particle size determination: None, vapor
- Temperature, humidity, pressure in air chamber: Mean of 23.2 C, 61.5% relative humidity, and oxygen concentrations ranging from 18.6-20.3%

TEST ATMOSPHERE
- Brief description of analytical method used: The test material and oxygen concentrations during the exposures were monitored in real time by gas chromatography (GC). An Agilent Model 490 micro GC was utilized for this study via thermal conductivity detector under isothermal conditions and the test material showed adequate sensitivity.
- Samples taken from breathing zone: No data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Computational toxicology was utilized to estimate a starting dose for the class method.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

0 ppm, 1,547 ppm (20.3 mg/L), 10,200 ppm (131.8 mg/L)

No. of animals per sex per dose:

3 males per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each animal was observed throughout the study to clinical signs of toxicity. All notable findings were recorded. Body weights were recorded for all animals prior to exposure and daily thereafter through the end of the observation period.
- Necropsy of survivors performed: yes, gross necropsy
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 20.3 - < 131.8 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

One rat had continuous seizures every 30 seconds for one hour and was subsequently euthanized 2 hours post-exposure; necropsy revealed foam and fluid-filled trachea and red fluid dripping from nares. The remaining 2 rats from the 10,200 ppm exposure group were found dead the following day, necropsy showed lungs were dark cherry red.

Clinical signs:

other: Rats exposed to 1,570 ppm (20.3 mg/L) of the test article demonstrated no adverse clinical signs of toxicity and all survived the 4 hour exposure and 14 day recovery period. During the 10,200 ppm (131.8 mg/L) exposure, adverse clinical signs included spo

Body weight:

No abnormal changes in body weight were noted in the animals exposed to 1,570 ppm (20.3 mg/L).

Gross pathology:

One rat had continuous seizures every 30 seconds for one hour and was subsequently euthanized 2 hours post-exposure; necropsy revealed foam and fluid-filled trachea and red fluid dripping from nares. The remaining 2 rats from the 10,200 ppm exposure group were found dead the following day, necropsy showed lungs were dark cherry red.

No findings were noted in the 1,570 ppm (20.2 mg/L) group upon necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, the 4-hour LC50 of the test article is greater than 20.3 mg/L (1,570 ppm) and less than 131 mg/L (10,200 ppm).

Executive summary:

Male rats (3/sex/group) received whole body exposure to control (ambient air), 1,570 ppm (20.3mg/L), or 10,200 ppm (132 mg/L) test article (vapor) for 4 hours. Rats exposed to 1,570 ppm test article demonstrated no adverse clinical signs of toxicity and all survived the 4 hour exposure and 14 day recovery period. During the 10,200 ppm test article exposure adverse clinical signs included sporadic movement, urinary incontinence, sneezing, lethargy, and prostrate posture with diminished response to noise stimuli. Following the 4 hour exposure rats exposed to 10,200 ppm test article demonstrated twitching/headshaking, lethargy, no grip strength, cool to the touch appendages, prostrate posture, and unkempt appearance. One rat had continuous seizures every 30 seconds for one hour and was subsequently euthanized 2 hours post-exposure; necropsy revealed foam and fluid-filled trachea and red fluid dripping from nares. The remaining 2 rats from the 10,200 ppm exposure group were found dead the following day, necropsy showed lungs were dark cherry red. Control animals demonstrated no adverse signs of clinical toxicity during the course of the study. Based on the results of the study, the 4-hour LC50 of the test article is greater than 20.3 mg/L (1,570 ppm) and less than 131 mg/L (10,200 ppm).