1,1,2,2,3,3,4,4,4-nonafluoro-N-(2-hydroxyethyl)-N-methylbutane-1-sulphonamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

T-7599

IUPAC Name:

T-7599

Details on test material:

- Name of test material (as cited in study report): T-7599
- Substance type: White powder
- Analytical purity: >99.9% 1-Butanesulfonamide, 1, 1, 2, 2, 3, 3, 4, 4, 4-Nonafluoro-n-(2-Hydroxyethyl)-N-Methyl; < 0.1% Methylamine.
- Lot/batch no.: Lot 6
- Expiration date of the lot/batch: 07 August 2002
- Stability under test conditions: Not indicated
- Storage condition of test material: At room temperature in the dark

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M Company, Lot 40066
- Expiration date of the lot/batch: 30 September, 2022
- Purity test date: 09 October, 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle: Homogenized in polyethylene glycol 400 (PEG 400)

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test article was homogenized in PEG 400
- Final preparation of a solid: Homogenized in PEG 400

Test animals

Species:

rat

Strain:

other: Wistar Han

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 9-12 weeks old
- Weight at study initiation: 177-201 g
- Fasting period before study: None
- Housing: On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) and following assignment to the study, animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. The room in which the animals were kept was documented in the study records. Animals were separated during designated procedures/activities. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Tap-water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 27-50%
- Air changes (per hr): 10 or greater
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03 December, 2018 To: 03 January, 2019

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: Polyethylene Glycol 400 (PEG 400)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- % coverage: 10
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with water following the 24 hour exposure
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- For solids, paste formed: Homogenized in PEG 400

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/kg body weight

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings. Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing. Animals were weighed individually on Day 1 (predose), 8 and 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred at 2000 mg/kg.

Clinical signs:

other: Chromodacryorrhoea (snout) was noted for one animal on Day 1 only. No other abnormal clinical findings were observed.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, the dermal LD50 of the test article is rats is greater than 2,000 mg/kg body weight.

Executive summary:

The acute dermal lethality potential of the test article was evaluated in female Wistar Han rats. The study was conducted according to OECD 402 (2017) in compliance with OECD GLP regulations. The test article was homogenized in polyethylene glycol 400 (PEG 400) prior to dosing so as to deliver 2,000 mg/kg body weight to each animal at a dose volume of 10 mL/kg body weight. One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped. The test item was applied in an area of approximately 10% of the total body surface, i.e. 18 cm² for females. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages. The application period was 24 hours, after which the dressing was removed and the skin cleaned of residual test item using water. Initially, the test article was administered to a single female Wistar Han rat by a single dermal application at 2000 mg/kg body weight for 24 hours in a range finder study. Based on the results, the main study was performed by dosing two females at 2000 mg/kg. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Chromodacryorrhoea (snout) was noted for one animal on Day 1 only. No irritation was noted for any of the animals at any time point. The body weight gain shown by the animals during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. Based on the results of the study, the dermal LD50 of the test article is rats is greater than 2,000 mg/kg body weight.