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Specific investigations: other studies

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specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliability: Medium because a suboptimal study design was used where animals were not individually titrated with adrenalin.

Data source

Reference Type:
review article or handbook
ECETOC Joint Assessment on Commodity Chemicals - 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) Cas No. 306-83-2 (3rd edition)
Malinverno G, Millischer R, Sarrif A, Schmit B, Trochimowicz H, Haebler W, Vrijhof H
Bibliographic source:
European Centre for Ecotoxicology and Toxicology of Chemicals, ISSN-0773-6339-47 - Brussels May 2005

Materials and methods

Test guideline
no guideline followed
GLP compliance:
not specified
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Constituent 2
Reference substance name:
Ethane, 2,2-dichloro-1,1,1-trifluoro-
Ethane, 2,2-dichloro-1,1,1-trifluoro-
Details on test material:
- Name of test material (as cited in study report): Trichlorodifluoroethane (Freon 123)
- Physical State: Gas

Test animals

Details on test animals or test system and environmental conditions:
no data

Administration / exposure

Route of administration:
other: air
Details on exposure:
The test animal received an intravenous control injection of adrenalin (0.008 mg/kg) prior to exposure and a challenge injection (same dosage) after breathing the compound for five minutes. Freon 123 is a liquid at room temperature and was generated from a syringe drive into a heated, metered, airstream. The compound-air mixture then passed into a heated one-liter mixing flask and subsequently to the dog mask. Exposure concentration (v/v in air) was sampled every 1 1/4 minutes and analyzed by a gas chromatograph employing a Porapak T column and a thermal conductivity detector.

Each dog was tested one at a time, in such a way that the results of any test was known before the next was begun. Each test was run at a concentration level different from the preceding one. Therefore, the staircase method (Finney, 1964) was the method of choice to estimate an EC50 for cardiac sensitization. With this statistical procedure, a series of concentrations was chosen, e.g. … X-2, X-1, X0, X1, X2 …, where X0 was the estimated EC50 and the values of X were equally spaced. The result of any one test determined the concentration level for the next test: if a dog exhibited a "marked response," the next dog was tested at a concentration one step lower, if the animal showed no "marked response," the next dog was tested at a level one step higher. The first test was run at X0. Using this method, a concentration of 4.0% (40,000 ppm) was chosen as the estimated X0 and concentrations selected below and above that level included 0.5 (5000 ppm), 1.0 (10,000 ppm), 2.0 (20,000 ppm), and 8.0% (80,000 ppm). A total of 12 individual dogs were used for this study.
Analytical verification of doses or concentrations:
Details on analytical verification of doses or concentrations:
Exposure concentration (v/v in air) was sampled every 1 1/4 minutes and analyzed by a gas chromatograph employing a Porapak T column and a thermal conductivity detector.
Duration of treatment / exposure:
5 minutes
Frequency of treatment:
single test
Doses / concentrationsopen allclose all
Doses / Concentrations:
10,000 ppm
nominal conc.
Doses / Concentrations:
20,000 ppm
nominal conc.
Doses / Concentrations:
40,000 ppm
nominal conc.
No. of animals per sex per dose:
three dogs were exposed to 10,000 ppm, six dogs to 20,000 ppm and three dogs to 40,000 ppm
Control animals:
not specified


An electrocardiogram was recorded during each experimental run and a "marked response" was noted when an arrhythmia developed which was considered to pose a serious threat to life (multiple consecutive ventricular beats or bigeminal rhythm) or which ended in cardiac arrest (ventricular fibrillation).

Results and discussion

Details on results:
Central nervous system depression (decreased motor reflexes, lassitude, etc. ) as well as tachycardia, prior to the challenge injection of adrenaline, occurred in the six animals that died as a result of this test. In the dog that exhibited a "marked response" and survived a 4.0% exposure, central nervoussystem excitation (struggling, tachycardia, labored respiration, etc.) preceded the challenge injection of adrenaline. Signs of central nervous system depression were also observed in the dogs that showed no positive response at 1.0 and 2.0% Freon 123. An EC50 for Freon 123 was calculated, along with 95% confidence intervals, and found to be 1.90% (19,500 ppm) (1.30-2.80% (13,000 - 28,000 ppm), 95% C.L.).

Applicant's summary and conclusion

Under the conditions of this study, the cardiac sensitization potential EC50 of Freon 123 (trichlorodifluoroethane) was determined to be 19,000 ppm in dogs.
Executive summary:

The cardiac sensitisation potential of HCFC-123 was evaluated in adrenaline-primed beagle dogs. Dogs were exposed to 10,000, 20,000 or 40,000 ppm (62,500, 125,000 or 250,000 mg/m3) HCFC 123. After approximately 5 minutes of exposure the dogs were given an intravenous injection of epinephrine (8 μg/kgbw) and monitored for cardiac arrhythmia. 3/3 dogs developed cardiac arrhythmia at an exposure level of 40,000 ppm and 4 out of 6 dogs after exposure to 20,000 ppm. A concentration of 10,000 ppm was tolerated without any signs of cardiac arrhythmia. The EC50 was estimated to be approximately 19,000 ppm (119,000 mg/m3) and the NOEL was 10,000 ppm for HCFC-123