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Skin irritation / corrosion

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Administrative data

skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
other: The protocol published by "Arrêté" of 1 February 1982 in the "Journal Officiel de la République Française" of 21 February 1982.
GLP compliance:
yes (incl. certificate)

Test material

Details on test material:
- Name of test material (as cited in study report): HFA 134a (1,1,1,2-tetrafluoroethane)
- Substance type: pure active substance
- Physical state: liquefied gas
- Analytical purity: >99.8%
- Purity test date: received 10 July 1989 2 x 250 ml and 22 September 1989 about 5 kg.
- Lot/batch No.: 00015 I9 001
- Stability under test conditions: yes
- Storage condition of test material: room temperature
- Other:

Test animals

New Zealand White
Details on test animals and environmental conditions:
- Source: Bancel (Albon - 26140 Saint-Rambert-d'Albon-France)
- Age at study initiation: Adult
- Weight at study initiation: 2.45 to 2.70 kg
- Housing: cages - housed individually in polystyrene cages with perforated flooring (internal dimensions 560 x 355 x 315 mm)
- Diet (e.g. ad libitum): About 150g per animal and per day of complete pelleted rabbit maintenance diet (U.A.R., Villemoisson - 91360 Epinay S/Orge - France).
- Water (e.g. ad libitum): filtered (15um) and softened mains drinking water (automatic dispenser). Bacteriological and chemical analysis twice a year.
- Acclimation period: 19 days before start of treatment

- Temperature (°C): 20 to 22°C
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12 (photoperiod 0730 to 1930 hrs).


Test system

Type of coverage:
Preparation of test site:
other: scarified and intact
unchanged (no vehicle)
Amount / concentration applied:
Liquefied gas, 0.5ml on each treated area per animal
Duration of treatment / exposure:
24 hours
Observation period:
The cutaneous examinations were performed approximately 30 minutes after removal of the occlusive patch and then again 48 hours later, that is approximately 24 and 72 hours after the application of the test substance.
Number of animals:
One single goup of 6 males
Details on study design:
Preparation of the treated area: the day before application of the test substance, the back and flanks of the rabbits were carfully clipped to expose an area approximately 14 cm x 14 cm.
Three parallel incisions appromimately 2cm long and 0.5cm apart were made parellel to the vertibral axis on the right flank of each rabbit using a sterile lancet. The incisions were performed to cut the epidermis without damaging the dermis and avoiding any bleeding.
The tests substance was applied to a square of Codex hydrophilic 8 layers thick and approximately 2.5 cm square and placed in a "capsule" to avoid loss of material.
Application was perfomed on the scarified area of the right flank and on the intact area of the left flank.
The test substance and gauze pad were held in contact with the skin with the aid of the polypropylene "capsule", which was 28mm wide and fixed by a micorporous adhesive band.
The capsule was further secured by an 8 cm wide adhesive band applied on strip of crepe gauze. This encircled the trunk, without restricting respiratory or abdominal movement, and completely covered the clipped area to avoid any possible irritant reactions. The rabbits were then placed in individual cages.
Scoring was carried out with the animals immobilised on a table under the same conditions of ambient light. Evaluation of both the scarified and intact sites was according to the criteria in Table 1.
At each observation period for each animal the total of the values obtained for erythema and oedema was calculated for the intact and scarified areas.
The sum of all vaues was calculated. The mean was determined by dividing the sum of all valuesl by the number of data (n=24). See Table 2.
The mean value thus obtained corresponds to the index of Primary Cutaneous Irritation (PCI).

Results and discussion

In vivo

Irritation parameter:
primary dermal irritation index (PDII)
Time point:
other: total for obsevations at 24 & 72 hours
Max. score:
other: At 72 hours following treatment a very slight oedema persited in one animal in a scarified area only. Erythema showed a good reversibility.
Remarks on result:
other: 24 hours after application a barely visible erythema was observed in 5/6 animals as well as a slight odema in 6/12 areas treated.
Irritant / corrosive response data:
Slight irritation to intact skin (See Table 2)

Any other information on results incl. tables

Table 2. Results of the HFC 134a Cutaneous Primary Irritation Test in the Rabbit
                         Evaluation of Irritation
 Rabbits  Zones         24 hours         72 hours  Total
     Erythema  Oedma  Total  Erythema  Oedema  Total   24&72 hr Ery + Oed
 55673 Intact  1  1  2  0  0  0  2
  Scarified   1  2  3  1  1  2  5
 55657 Intact  1  0  1  0  0  0  1
  Scarified  1  1  2  0  0  0  2
 55655 Intact  1  0  1  0  0  0  1
  Scarified  1  0  1  0  0  0  1
 55672 Intact  0  0  0  0  0  0  0
  Scarified 0  0  0  0  0  0
 55668 Intact  1  2  0  0  0 2
  Scarified 1  1  2  1  0  1 3
 55658 Intact  1  0  1  1  0  1  2
  Scarified  1  1  2  0  0  0  2
                       Total (t)  21
  Total No. of data (d) 24 
Cutaneous Primary Irritation Score (PCI) (t/d) = 21/24  0.88
Table 3. Expression of Results
 Primarty Cutaneous Index PCI Classification of the test substance
 PCI < / = 0.5 Non-irritant
 0.5 < PCI < / = 2 Slightly irritant
 2 < PCI  < / = 5 Irritant
 5 < PCI < / = 8 Very Irritant

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Migrated information Criteria used for interpretation of results: other: according to the calculated primary cutaneous irritation index and the table published in the "Journal Officiel de la République Française" ( 21 February 1982)
Primary Cutaneous Irritation Index (P.C.I.) = 0.88.
From this result obtained under the test conditions used, when applied to the skin of the rabbit in liquid form HFC 134a may be considered slightly irritant.
HFC 134a did not provoke any noticeable pathological cutaneous lesion.
Executive summary:

Liquefied HFC-134a (0.5 ml per application site) was applied on to a square of 8 layers of thick gauze pads. The gauze pads were placed on scarified and intact skin areas of rabbits, covered with an occlusive polypropylene film and fixed with an adhesive tape. Slight irritation to intact skin, possibly due to local freezing, appeared after 24 hours of contact.