Carbonyl difluoride

Endpoint summary

Description of key information

The results of a reliable study showed a 4-hour LC50 around 34.3 ppm. The result was supported by results of other less documented studies indicating that the 4-hour LC50 is below 100 ppm, and the 1-hour LC50 is approx 360 ppm.

Analytical information indicated negligible formation of hydrogen fluoride under the conditions of the study.

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:

1976-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: the test consists in determining the concentration expected to cause death in 50% of the treated animals.
- Short description of test conditions: 7 groups of rats were exposed to a single exposure of carbonyl fluoride at increasing concentrations for 4 hours to determine the LC50.
- Parameters analysed / observed: mortality, clinical signs, gross pathology

GLP compliance:

not specified

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: In-house source, Batch No. 9990
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL: no data

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: 240-260g
- 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: cylindrical (12" diameter) Plexiglass chamber
- Exposure chamber volume: 20-liter
- Source and rate of air: 20-liter/minute
- System of generating atmosphere: test atmosphere was generated by syringe driving COF2 into a dilution air stream passing through a Teflon line, and introduced through the top of the 20-liter cylindrical chamber and exhausted through a hole in the bottom of the chamber.
- Treatment of exhaust air: vacuum exhaust, no further details
- Temperature, humidity, pressure in air chamber: 45% humidity (average)

TEST ATMOSPHERE
- Brief description of analytical method used: Infra-red analysis using Miran IR analyser. The method can discriminate HF from COF2, thus allowing to assess the extent of hydrolysis of COF2 to HF.
- Samples taken from breathing zone: no information

VEHICLE
- Composition of vehicle (if applicable): air

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

measured concentrations: 26.7 to 47.6 ppm (v/v) (see result table)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: not specified
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes, gross pathology on 3 rats (basis of selection not provided)
- Other examinations performed: clinical signs

Statistics:

no data

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

34.3 ppm

Based on:

test mat.

95% CL:

>= 23.3 - <= 40.4

Exp. duration:

4 h

Mortality:

Reported in the table

Clinical signs:

other: Few clinical signs were observed. Rapid shallow to convulsive respiration occurred, varying with exposure concentration.

Gross pathology:

Examination of 3 rats (no details on corresponding concentration, and whether they were among the surviving animals):
Observation of white plaques, red focal spots, consolidation and edema of the lungs. Liver congestion and bright red spleens.

Analysis of chamber samples by infrared analysis to discriminate HF from COF2 indicated an average concentration of 48.8 ppm of COF2, with no detection of HF. The rate of hydrolysis to HF was negligible under the test conditions. Thus the acute inhalation toxicity cannot only be attributed to the formation of hydrogen fluoride.

Results :

analytical concentration (TWA) (ppm COF2, v/v)	sd  (ppm COF2, v/v)	mortality observed (number of dead animals/total in test group)
26.7	4.1	5/10
30.8	3.3	3/10
32.7	1.7	3/10
41.3	6.7	6/10
44.7	6.2	8/10
47.2	4.6	9/10
47.6	6.8	6/10

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

The 4-hour acute LC50 for gaseous carbonyl fluoride was determined to be 34.3 ppm (v/v) in air.

Executive summary:

Carbonyl fluoride was assessed in an acute inhalation toxicity study in rats. Seven groups of 10 males and 10 females were exposed for 4 hours (whole body) to increasing concentrations (26.7 to 47.6 ppm v/v) of carbonyl fluoride to determine the LC50.

Animals were observed for mortality, clinical signs. The gross pathology examination performed on 3 rats (no details on corresponding concentration, and whether they were among the surviving animals) showed white plaques, red focal spots, consolidation and edema of the lungs, liver congestion and bright red spleens.

The LC50 was determined to be 34.3 ppm (v/v) in air.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

92.4 mg/m³

Quality of whole database:

The results of a reliable study showed a 4-hour LC50 around 34.3 ppm. The result was supported by results of other less documented studies indicating that the 4-hour LC50 is below 100 ppm.

Additional information

Carbonyl fluoride is predicted to hydrolyse in the presence of water or moisture to hydrogen fluoride and carbon dioxide. However, it seems the acute toxicity of carbonyl fluoride is greater than that of hydrogen fluoride that would be released by hydrolysis.

Pathological examination provided evidence of inflammation and signs of pulmonary oedema following a single administration, indicating that the gas could reach the deeper airways. Focal haemorrhage may be indications of local corrosivity.

Alveolar damages seen following a 1-hour exposure at 360 ppm were reversible (Scheel et al., 1968).

Justification for classification or non-classification

The results of a reliable study showed a 4-hour LC50 around 34.3 ppm. The result was supported by results of other less documented studies indicating that the 4-hour LC50 is below 100 ppm.

Thus the classification for carbonyl fluoride is Acute Toxicity cat. 1, H330: Fatal if inhaled.

There is no sufficient information at non-lethal concentration levels to justify a STOT SE classification.

However, as the acute toxicity observed may be related to the corrosive potential of the hydrogen fluoride expected to be formed from hydrolysis of carbonyl fluoride in the presence of moisture, the supplemental labelling statement EUH071: ‘corrosive to the respiratory tract’ is considered appropriate.