2,3,3,3-tetrafluoro-2-[1,1,2,2,3,3,4,4-octafluoro-4-(fluorosulfonyl)butoxy]propanoyl fluoride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,3,3,3-tetrafluoro-2-[1,1,2,2,3,3,4,4-octafluoro-4-(fluorosulfonyl)butoxy]propanoyl fluoride

EC Number:

833-066-1

Cas Number:

117516-16-2

Molecular formula:

C7F14O4S

IUPAC Name:

2,3,3,3-tetrafluoro-2-[1,1,2,2,3,3,4,4-octafluoro-4-(fluorosulfonyl)butoxy]propanoyl fluoride

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: 3M Company, lot 20005
- Purity, including information on contaminants, isomers, etc.: 96.2%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage: No data
- Stability in the medium, i.e. sensitivity of the test material to hydrolysis and/or photolysis: No data
- Solubility and stability of the test material in the solvent/vehicle and the exposure medium: No data
- Reactivity of the test material with the incubation material used (e.g. plastic ware): No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): solubolized in perfluorohexane for 50 mg/kg dose; for all other doses, the test article was applied unchanged
- Preliminary purification step (if any): No data

FORM AS APPLIED IN THE TEST: administed unchanged for 300 and 2000 mg/kg doses and solubolized in perfluorohexane for 50 mg/kg dose

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 146-192
- Fasting period before study: No data
- Housing: All rats were group housed in solid bottom cages.
- Historical data: No data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data
- Method of randomisation in assigning animals to test and control groups: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 72 ± 3°F
- Humidity (%): 30 – 70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 2020/07/22 To: 2020/10/06

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

at 50 mg/kg dose, vehicle was perfluorohexane

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 mg/kg dose in vehicle only
- Amount of vehicle (if gavage): 0.057 mL of test article mixed with 9.943 mL perfluorohexane
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: No data

DOSAGE PREPARATION (if unusual):
The test material was dosed “neat” via oral gavage for the 300 and 2,000 mg/kg dose levels. The dose volumes per animal were calculated in the following manner:(BW (kg) X (Dose Level in mg/kg))/(Density X 100) = mL test material to administer
For 50 mg/kg, the test material was dosed in a perfluorohexane vehicle via oral gavage. The dose volumes per animal were calculated in the following
manner: 0.057 mL of MTDID 32950 mixed with 9.943 mL perfluorohexane, (BW (kg) X (5 mL/kg)) = Dose in mL

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on the chemistry of the test article and professional judgement

Doses:

1

No. of animals per sex per dose:

1 female/dose in sighting study; 6 females/dose in follow-up study for 50 and 300 mg/kg doses

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily clinical observations, weekly weighing
- Necropsy of survivors performed: yes
- Clinical signs including body weight : clinical observations, body weights, and gross necropsy:

Statistics:

There were no statistical analyses were performed

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mL/kg bw

Based on:

test mat.

Mortality:

No animals survived the 2000 mg/kg dose. Four of 6 animals survived the 300 mg/kg dose. All 6 animals survived the 50 mg/kg dose with no clinical signs of toxicity noted throughout the 14-day post-dose recovery period.

Clinical signs:

other: The animal dosed at 2,000 mg/kg exhibited lethargy and labored breathing approximately 15 minutes post dose. The animal was deceased approximately 30 minutes post dose. The animal dosed at 300 mg/kg displayed no clinical adverse signs of toxicity up to 7-

Gross pathology:

Upon macroscopic examination at gross necropsy, the animal dosed with 2,000 mg/kg test article displayed stomach tissue was white with areas of dark red. The liver was dark red with light red patches throughout. One animal in the 300 mg/kg test article dose group that was euthanized in extremis approximately 2 hours post-dose displayed bright reg lungs and a swollen stomach, containing colorless liquid, that appeared inflamed on the caudal side. A second animal in this group that was found dead in cage 2 days post-dose displayed red lungs with red discoloration in spots on the stomach. Four of the 6 surviving animals in the 300 mg/kg dose group had no significant findings or gross lesions during necropsy at the conclusion of in-life. There were no test material-related lesions identified in the animals dosed at 50 mg/kg test article upon gross necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 of CASRN 117516-16-2 is greater than 300 but less than 2,000 mg/kg.

Executive summary:

The acute oral toxicity potential of CASRN 117516-16-2 was assessed in an OECD Guideline 423: Acute Oral Toxicity – Acute Toxic Class Method. In the sighting study, two female Sprague Dawley rats were dosed with either 300 or 2000 mg/kg unchanged via oral gavage. The animal dosed with 2000 mg/kg was deceased approximately 30 minutes post dose, and the animal dosed with 300 mg/kg displayed no clinical adverse signs of toxicity up to 7-days post-dose. An additional 5 females received 300 mg/kg unchanged test article via oral gavage. 4 of the 6 animals dosed with 300 mg/kg survived to the end of the study period and had no significant findings or gross lesions during necropsy at the conclusion of in-life. Due to death shortly after administering both initial dose levels, an additional single animal was administered 50 mg/kg test article in perfluorohexane vehicle. This single animal displayed no clinical signs of toxicity after dosing and continued to gain weight for 7 days post-dose, so an additional 5 animals were dosed at 50 mg/kg. All 6 female rats dosed at 50 mg/kg test article displayed no clinical signs of toxicity and had body weight measurements taken over a 14-day recovery period. Under the conditions of this study, the acute oral LD50 of CASRN 117516 -16 -2 is greater than 300 but less than 2,000 mg/kg.