difluoro(fluorosulphonyl)acetyl fluoride and 3,3,4,4-tetrafluoro-1,2-oxathietane 2,2-dioxide

Endpoint summary

Description of key information

An acute inhalation study is available on the substance. The atmosphere was generated from vapours of the substance heated at 40°C, with tubing leading to the exposure chamber kept above 29°C. The LC50 (4hrs) was 220 ppm. Clinical and pathological examinations showed evidence of irritation and corrosion in particular on skin, eyes and in the lung.

Key value for chemical safety assessment

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974 (no details)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

- Principle of test: similar to standard test methods. Groups of 6 males were exposed to a gaseous atmosphere of the test substance at 5 different concentrations.
- Short description of test conditions: 4 hour exposure followed by a 14-day post-exposure period.
- Parameters analysed / observed: lethality, clinical signs, gross pathology and micrscopic examination.

GLP compliance:

not specified

Remarks:

Prior to GLP standards

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

fluorosulfonyl difluoroacetyl fluoride, boiling point 29°C
For the study, the test material was kept in the gaseous state (BP 29°C) by heating the cyclinder to 40°C

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 250-300 g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: not specified

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the cylinder containing the test material was placed in an upright mutliple unit electric furnace heated to 40°C and controled by a Pyr-o-vane controller. Concentration was regulated by dual valve system. Stainless steel tubing, enveloped in heating tapes to keep the temperature above 29°C, led to the top of the exposure chamber.
- Exposure chamber volume: 20 liters
- Air flow: 2.4L/minute N2 and 0.6 L/Minute O2
- Temperature, humidity, pressure in air chamber: no data

TEST ATMOSPHERE
Test chamber air was drawn by vacuum pump into midget impingers containing 10 ml of 0.05 NaOH. Samples were read on a Beckman pH meter with a fluorine selective elctrode and compared to a standard curve (w/v) of the substance in 0.05 NaOH.

VEHICLE
- Composition of vehicle: air
- Chamber O2: 18-20%, checked with a Beckman O2 meter.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

135, 226, 272, 872, 1790 ppm (v/v)

No. of animals per sex per dose:

6 males/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no details
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
- Histopathology on the following tissues: lung, trachea, bronchi, liver, kidney, testis, epididymis, thymus, thyroid, adrenal, esophagus; stomach, intestine, heart, pancreas, brain, eye, bone marrow, skin (ear).

Statistics:

The LC50 was determined by the Litchfield-Wilcoxon method

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 220 ppm

Based on:

test mat.

95% CL:

>= 176 - <= 275

Exp. duration:

4 h

Mortality:

Animals exposed to the highest concentration died during the exposure period.
See details in result table.

Clinical signs:

other: At lethal concentration: erythema, gasping, corneal opacity, hypersensitivity to touch At non-lethal concentrations: red eyes, increased respiration

Body weight:

The weight was recorded, but no figures provided in the report.
At high concentrations there was a moderate to severe weight loss for several days post-exposure, followed by slow weight gain.

Gross pathology:

see result table

Other findings:

- Histopathology: tubular cell necrosis was observed in the animals of the high concentration, and in the surviving rat of the 272 ppm group
- Potential target organs: kidney
- Other observations: corneal opacity was reported in several animals at lethal concentrations, and in one surviving animal of the 226 ppm group.

Table 1 - results

concentration (ppm v/v)	lethality	comments	gross pathology	histopathology
135	0/6			no unusual findings
226	3/6	1 died within 72 hours, 2 died within 96 hours post-exposure	1 of the surviving rats had bilateral corneal opacity	no unusual findings in the 3 surviving rats after 14-day post-exposure No pathological examination was performed on the 3 rats that died 5 days post exposure due to putrefied condition
272	5/6	2 died during exposure, 2 died within 48 hours, 1 died 96 hours post-exposure		- kidney: renal tubular cell necrosis in the surviving rat
872	6/6	3 died during exposure, 3 died within 24 hours post-exposure	(not examined)	(not examined)
1790	6/6	died during exposure	- bilateral corneal opacity in 2 rats (out of 2 examined) - moderate subcutaneous edema in the ear skin of 2 rats (2 examined)	- lung: intra-alveolar hemorrhage - kidney: focal cortical tubular cell necrosis - thymus: moderate to marked focal hemorrhage

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The 4-hour acute LC50 for fluorosulfonyl difluoroacetyl fluoride was determined to be 220 ppm (v/v) in air.

Executive summary:

Fluorosulfonyl difluoroacetyl fluoride was assessed in an acute inhalation toxicity study in rats. Five groups of 6 males were exposed for 4 hours (whole body) to increasing concentrations (135 to 1790 ppm v/v) of Fluorosulfonyl difluoroacetyl fluoride in a gaseous form to determine the LC50.

Animals were observed for mortality and clinical signs for 14-day post-exposure.

In the groups exposed to the two highest concentrations, all the animals died during the exposure period, or within 24 hours (3 animals in the 872 ppm group). At the lethal concentrations, animals displayed erythema, gasping, corneal opacity and hypersensitivity to touch, and at the non-lethal concentrations, red eyes and increased respiration.

Gross pathology examination of some of the animals of the highest concentration rats showed corneal opacity and subcutaneous edema in the ear skin.

Microscopic examination showed in the dead animals of the high concentration group intra-alveolar haemorrhage to the lung and focal haemorrhage in the thymus. Focal cortical tubular necrosis (kidney) was seen in animals of the high concentration and in the surviving animal of the group exposed to 272 ppm. All animals of the lowest concentration (135 ppm) survived with no unusual changes.

The LC50 was determined to be 220 ppm (v/v) in air. Clinical and pathological examinations showed signs of irritation and/or corrosion.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 617 mg/m³

Quality of whole database:

The study was conducted according to a method similar to guidelines.

Additional information

Signs of irritating or corrosive effects on skin, eyes, lungs indicates that the toxicity may be related to corrosive properties of the test material, most likely following hydrolysis in the presence of moisture to form hydrogen fluoride and 2,2-Difluoro-2-(fluorosulfonyl)acetic Acid.

Therefore, studies by other routes of exposure (oral, dermal) are not considered appropriate.

Justification for classification or non-classification

The 4-hour LC50 of 220 ppm (1.617 mg/L) in male rats obtained in a reliable acute inhalation toxicity study triggers a classification as acute toxic category 2, H330 according to criteria in Regulation (EC) No. 1272/2008 for the Classification, Labelling and Packaging of Substances and Mixtures (CLP/EU GHS).

Damage to the renal tubular cells were observed at lethal concentration (highest concentration) and there was no sufficient information at non-lethal concentrations to justify a STOT SE classification.

As the macroscopic and microscopic observations indicate that the toxicity could be related to the corrosive potential of the test material, the supplemental labelling statement EUH071: "corrosive to the respiratory tract" is deemed appropriate.