Reaction mass of potassium trifluoroacetate and potassium trifluoromethanesulphinate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 Oct 2019 to 18 Jun 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

2019-02-11

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of potassium trifluoroacetate and potassium trifluoromethanesulphinate

EC Number:

911-467-3

Molecular formula:

C2O2F3K and CO2F3KS

IUPAC Name:

Reaction mass of potassium trifluoroacetate and potassium trifluoromethanesulphinate

Constituent 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Details on test material:

- Appearance: Yellow to slightly brown liquid
- Analytical purity: 30%
- Impurities (identity and concentration): Sulfates 0.02%; Sulfites 0.08%; Dimethylformamide 0.06%
- Composition of test material, percentage of components: Potassium triflinate (TFSK) 14.2%, Potassium trifluoroacetate (TFAK) 14.8%, Water: to complete the composition
- Purity test date: 2019-02-13
- Lot/batch No.: SSK1904360
- Expiration date of the lot/batch: March 27, 2022
- Storage conditions: Room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF (Beijing) Biotechnology Co., Ltd
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 339-368 g (males) and 219-224 g (females)
- Housing: Suspended, stainless steel cages (L32xW28xH20 cm); housed individually
- Diet: SPF Rodent Maintenance Feed (Shenyang Maohua Biotechnology Co., Ltd), ad libitum (except during exposure)
- Water: Purified water, ad libitum (except during exposure)
- Acclimation period: 10 days. Animals were acclimated for the restraining tubes twice prior to dosing in order to minimize stress. First pre-adaptation was about 1 hour, second pre-adaptation was about 2 hours. No abnormalities were found.
- Method of randomisation in assigning animals to test and control groups: use of Excel's random function

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.3 - 24.9°C (target value 20 - 25°C)
- Humidity (%): 27-63% (target value: 40-70%)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

snout only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber: Small animals snout-only aerosol inhalation system was used. Before exposure, each rat was restrained in a confined transparent polyacrylic tube. The exposure tubes were installed in the portholes of the inhalation chamber and the chamber was sealed up. Filtered and compressed air was mixed with quantitative test item and aerosol was sent to the exposure chamber (0.0014 m3). The aerosol was continuously generated from a generation system on the top of the chamber with an aerosol producer. A slight negative pressure was maintained in outer plenum of the chamber to prevent leakage to the surrounding area. The exhaused air was removed from the outlet at the bottom of the chamber to an absorption unit. During the exposure, chamber airflow, chamber temperature, relative humidity, concentration of oxygen and carbon dioxide were determined.

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: Constituent components of the test item were determined by high performance liquid chromatographic (HPLC) analysis method. Samples were collected by U type porous glass plate absorption tube with 10 ml ultra-purified water. Frequency of determination was at least 1 time within 4 hours. According to the analysis results, the components of the original sample and inhalation sample were consistent. Actual concentration at the animal's breathing zone was determined by using gravimetric analysis. Samples were collected by using a filter fixed in a filter holder attached the the sample zone of the inhalation chamber (airflow of 1 L/min, 5 min and volume of 5 L). Frequency of determination was about once per hour. The total used mass of the test item was divided with total passed through air volume during the exposure period. The particle size distribution of the test atmosphere was determined by using an Aerosol Instrument for Aerodynamic Particle Sizer (APS 3321).
- Samples taken from breathing zone: yes

VEHICLE
No vehicle used except air.

TEST ATMOSPHERE
- Particle size distribution: The aerodynamic particle sizes less than 4 micro (mass%) for two times measurement was 56.59 and 58.87%, respectively.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD for the two times measurement was 3.19 µm and 2.94 µm, respectively. The geometric standard deviation (GSD) was 2.18 and 1.94, respectively.

CLASS METHOD
- Rationale for the selection of the starting concentration: Based on the available data showing low acute toxicity (Acute Oral LD50 >2000 mg/kg) and according to OECD Guideline 436, 5000 mg/m3 was selected as starting concentration.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrically measurement

Duration of exposure:

4 h

Concentrations:

5000 mg/m3 (target concentration)

No. of animals per sex per dose:

3/sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: Clinical observations were recorded once during the exposure and twice with more than 30 minutes interval after exposure on the exposure day and then once daily to the end of the observation period.
Body weights: The animals were weighed in the first 24 hours after arrival, prior to exposure (day 0), day 1, 3, 7 and day 14.
- Necropsy of survivors performed: yes. All surviving animals at the end of the study were subjected to gross necropsy.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 040 mg/m³ air (analytical)

Based on:

act. ingr.

Exp. duration:

4 h

Mortality:

No animals were found dead during the test period.

Clinical signs:

other: Directly after exposure, symptoms of moist fur, moist chest and abdomen, soiled perineal region were found in 2 female animals. No abnormalities were found in other animals during the obervation period.

Body weight:

The body weight of all females and 2 males decreased on Day 1 after exposure and increased on Day 3.

Gross pathology:

No abnormalities were found in female and male animals at gross necropsy.

Any other information on results incl. tables

Test atmosphere characterization:

The actual mean concentration in the exposure cabinet of the four times measurement was 5040 ± 118 mg/m3. Nominal concentratino in the cabinet was 23396 mg/m3.

The value of air flow of exposure was 16.79 L/min. The temperature, relative humidity, oxygen and carbon dioxide concentration were considered appropriate for exposure.

Deviation from protocol:

One detection point of the relative humidity was 27% which deviated from the study plan (40 -70%). The time of the deviation was short and no abnormalities were found in animals during the test.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, the acute inhalation LC50 of the Reaction Mass of TFSK/TFAK in rats was established to be higher than 5040 mg/m3.

Executive summary:

An assessment of the acute inhalation toxicity of the Reaction mass of TFSK/TFAK to Sprague-Dawley rats was realized according to the OECD 436 guideline (Acute Toxic Class Method) and under GLP conditions.
TFSK TFAK Reaction mass was administered at 5040 mg/m3 concentrations to 6 animals (3 males and 3 females) for 4 hours by snout-only inhalation. Clinical observations were made once during exposure and twice after exposure on the dosing day and then once daily during the 14 days observation period. Body weights were determined on day 0, 1, 3, 7 and 14. Concentrations were analysed four times and particle size distributions were measured two times during exposure. Macroscopic examination was performed to all animals at the end of observation.

The actual mean concentration in the exposure chamber was 5040 ± 118 mg/m3. The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (GSD) for the two times measurement was 3.19 µm (GSD 2.18) and 2.94 µm (GSD 1.94), respectively. The aerodynamic particle sizes less than 4 micron (mass%) for the two times measurement was 56.59 and 58.87%, respectively.

No animals were found dead during the test period. The body weight of all females and most males decreased on Day 1 after exposure and increased on Day 3. No abnormalities were found in female and male animals at gross necropsy. Based on the results, the acute inhalation LC50 in SD rats for the Reaction mass of TFSK/TFAK was established to be higher than 5040 ± 118 mg/m3