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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: the protocol of Guillot-Gonnet-Clément-Brulos published by the AFNOR: FD n° T03-300, 1982
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
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: June 1989
- Lot/batch No.: 00015 I9 001 ex Piere-Bénite/Allied
- Expiration date of the lot/batch: n/a
- - Stability under test conditions: Stable
- Storage condition of test material: storage in original container, protected from heat.
- Other:

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Lebeau
- Age at study initiation: young Adult
- Weight at study initiation: 381 to 492 g (main study)
- Housing: housed by sex in groups of 5 or 6 (or 2 in preliminary studies) in polystyrene cages with perforated flooring (internal dimensions 560 x 335 x 315 mm)
- Diet (e.g. ad libitum): ad libitum, complete pelleted guinea-pig maintenance diet (U.A.R. formula 114 - U.A.R., Villemoisson - 91360 Epinay-S/Orge - France).
- Water (e.g. ad libitum): ad libitum (automatic watering), filtered and softened mains drinking water. Bacteriological and chemical analysis twic a year.
- Acclimation period: preliminary study: 26 days before beginning treatment; main study: 18 days before beginning treatment


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.5 to 22.5
- Humidity (%): 25 to 62
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12 (photo period 07.30 to 19.30 hrs)


IN-LIFE DATES: From: To:

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 ml liquefied HFA 134a
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 ml liquefied HFA 134a
No. of animals per dose:
10 males and 10 females in main study
Details on study design:
RANGE FINDING TESTS: to determine maximum non-irritant dose level to be used in main test.
One group of 2 males and 2 females
Dose levels 0.25 and 0.50 ml of HFA 134a applied to the clipped skin of dorsal region under an occlusive bandage for 48 hours.
Cutaneous examinations were performed 6, 24 and 48 hours after removal of the bandages.
0.5 ml HFA 134a produced no macroscopic reaction in the 4 guinea pigs examined and therefore was chosen as the dose level for the main study.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 7
- Exposure period: 48 hours Days 1,3,8,10 &15; 72 hours Days 5 and 12
- Test groups: 10 male and 10 female
- Control group: no
- Site: upper clipped costal region immediately behind the right scapulum
- Frequency of applications: Days 1, 3, 5, 8, 10, 12 & 15
- Duration: 48 or 72 hours
- Concentrations: 0.5 ml


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 29
- Exposure period: 48 hours
- Test groups: 10 male and 10 female
- Control group: no
- Site: left lateral abdominal region, not previously treated
- Concentrations:
- Evaluation (hr after challenge): 6, 24 and 48 hours after removal of occluisve dressing


OTHER:
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
6
Group:
test group
Dose level:
0.5 ml
No. with + reactions:
0
Total no. in group:
18
Clinical observations:
3 animals were found dead during the study with causes not related to treatment. Only one was replaced giving a total of 18 animals examined.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 6.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 18.0. Clinical observations: 3 animals were found dead during the study with causes not related to treatment. Only one was replaced giving a total of 18 animals examined..
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5 ml
No. with + reactions:
0
Total no. in group:
18
Clinical observations:
as above
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 18.0. Clinical observations: as above.
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5 ml
No. with + reactions:
0
Total no. in group:
18
Clinical observations:
as above
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 18.0. Clinical observations: as above.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Evaluation of the cutaneous delayed hypersensitivity of HFC 134a was performed in the albino Dunkin-Hartley guinea pig according to a maximised protocol using one treated group of 20 animals of both sexes.
0.5 ml of HFA 134a per guinea pig was administered for the 7 applications of the induction phase and the single challenge application.
Macroscopic examinations were performed on he application site 6, 24 and 48 hours following removal of the occlusive bandage.
HFA 134a did not provoke any cutaneous sensitisation reaction.
Executive summary:

Guinea pigs received one single intradermal injection of Freund's complete adjuvant followed by 7 occlusive epicutaneous administrations of 0.5 ml of liquefied HFC-134a, which was applied to the occlusive bandage before it was put in place, every 2 or 3 days over a 15-day period. The treated occlusive bandage was left in place between each application. After a period of 12 days without treatment, the challenge administration was performed by occlusive epicutaneous treatment with 0.5 ml of liquefied HFC-134a. No evidence of skin sensitisation was observed.