Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1974

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

Test animals

Species:
rat
Strain:
other: ChR-CD
Sex:
male
Details on test animals 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

Administration / exposure

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

Results and discussion

Effect levels
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.