1,1-difluoroethane

Endpoint summary

Description of key information

Inhalation: Acute Lethal Concentration (ALC) Test; rat; NOAEC = 66400 ppm (179280 mg/m3). Reliability = 2

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Principles of method if other than guideline:

Male rats were exposed to the test substance at 6.64, 17.52, 31.9, 38.3, and 45.75% for 4 hours and were observed for 14 day after treatment. Gross pathology was performed on surviving rats after 14 days.

GLP compliance:

not specified

Test type:

other: Acute Lethal Concentration (ALC) Test

Limit test:

no

Species:

rat

Strain:

other: Chr-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: 240-297 g
- Fasting period before study: No
- Housing: Not reported
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum): Not reported
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Route of administration:

inhalation: gas

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure chamber; no further details provided
- Exposure chamber volume: Not reported
- Method of holding animals in test chamber: Not reported
- Source and rate of air: Not reported
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: The gas was regulated through a calibrated flowmeter into a mixing chamber. Regulated flows of air and/or oxygen were used as the carrier gas from the mixing chamber to the exposure chamber. For the exposure with an analytical concentration of 6.64% (v/v), only air was used as the carrier gas. Starting with the 17.52% exposure, the chamber oxygen concentrations were 16-17%, which can cause hypoxemic symptoms. All subsequent exposures had oxygen added in an amount sufficient to maintain a chamber oxygen concentration of ~20%.
- Treatment of exhaust air: Not reported
- Temperature, humidity, pressure in air chamber: Not reported

TEST ATMOSPHERE
- Brief description of analytical method used: Atmospheres were sampled at 30-minute intervals and analyzed by thermal conductivity gas chromatography. Concentrations were determined from a standard curve.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Thermal conductivity gas chromatography

Duration of exposure:

4 h

Concentrations:

6.64, 17.52, 31.9, 38.3, and 43.75%. (66400, 175200, 319000, 383000, and 437500 ppm)

No. of animals per sex per dose:

6 males per concentration

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Not reported
- Frequency of weighings: Not reported
- Necropsy of survivors performed: yes

Sex:

male

Dose descriptor:

LC50

Effect level:

> 43.75 other: % (437500 ppm)

Exp. duration:

4 h

Remarks on result:

other: Mortality in 2/6 at 43.75% and 1/6 at 38.3%. At ≥ 17.52% lethargy, laboured breathing, reduced responsiveness to sound were observed. At 6.64% only hyperaemia and shallow breathing were observed.

Mortality:

Mortality ratio of 1/6 occurred at 38.3% (383000 ppm) and 2/6 occurred at 43.75% (437500 ppm).

Clinical signs:

other: Shallow breathing and hyperaemia were observed at 6.64%. During subsequent exposures additional signs observed included laboured breathing, lethargy, and unresponsiveness to sound were observed during exposure. Laboured breathing was more noticeable as

Gross pathology:

No gross changes were observed.

Conclusions:

The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

4-hour ALC = 38.3% (v/v) with oxygen added to maintain a chamber level of ca. 20% O2.

Executive summary:

Male rats were exposed to 6.64, 17.52, 31.90, 38.3, or 43.75% (v/v) (66400, 175200, 319000, 383000 or 437500 ppm) of the test substance for 4 hours and were observed for 14 days. At the end of 14 days all surviving rats were given a gross necropsy. The 4-hour ALC (approximate lethal concentration) was 38.3% (v/v; 383000 ppm) with oxygen added to maintain a chamber level of ~20%.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

179 280 mg/m³ air

Additional information

Toxicity Description: The substance has low inhalation toxicity with a rat 4-hour LC₅₀ value of greater than 437500 ppm. During inhalation to substance concentrations of 175200 ppm and higher, acute toxicity was associated with laboured breathing, lethargy and reduced responsiveness to sound. All effects resolved quickly at termination of exposure. There was mortality in 1/6 animals and 2/6 animals in the 383000 and 437500 ppm exposure groups, respectively.

Dose-response relationship: The acute systemic toxicity effects were observed in a dose dependent manner, but resolved quickly after exposure. This substance is a gas, and tests to evaluate dermal and oral systemic toxicity were not feasible.

Dose Descriptor: NOAEC for significant systemic effects resulting from acute inhalation exposure was 6.64% (66400 ppm).

Justification for selection of acute toxicity – inhalation endpoint
Acute Lethal Concentration (ALC) Test, Reliability = 2

Justification for classification or non-classification

Based on the rat 4-hour LC₅₀ greater than 437500 ppm (1181250 mg/m³) and the observations during the acute inhalation exposure, the substance does not need to be classified for acute toxicity according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.