Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP methodology followed and OCED guideline 406 used to performed the experiment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
The test article was applied to 9 animals instead of 10 animals in the control group during the challenge of the main study (amount of test article insufficient).
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
semi-solid (amorphous): gel
Remarks:
migrated information: paste
Details on test material:
- Identification: FAT 92267/A.
- Identification for the study: 01255 G3 002
- Presentaion: Light yellow powder.
- Purity: 81.1%
- Batch number: 3.86
- Packaging: Plastic container
- Quantity received: 100 gr.
- Date of receipt: 7 July 1993
- Storage: Room temperature.
- Expiry date: August 1994.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Albino Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hartley guinea-pig, supplied by Charles River France (Saint-Aubin-Les-Elbeus, 76410 Cleon, France.
- Age at study initiation: Young adult (about 6 weeks)
- Weight at study initiation: 250-550 gr
- Housing: Animals housed in groups according to EEC/86/609 in stainless steel mesh cages (internal dimensions 500x600x200 mm).
- Diet : Pelleted complete guinea-pig diet ad libitum (Diet reference 114 C - Usine d'Alimentation Rationnelle, Villemoisson, 91360 Epinay-sur-Orge, FRANCE),
- Water : Softened and filtered 0.2 micrometer mains drinking water, ad libitum (via automatic system)
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 190+/- 3°C
- Humidity (%): >=45%
- Air changes (per hr): >= 22 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial)/ 12 hours dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Treated group:
By intradermal route : 3 series of 2 x 0.1 ml injections
- Freund's complete adjuvant at 50 % (V/V) in an isotonic injectable solution.
- test article in a 0.1 % (W/W) solution in sterile Codex liquid paraffin.
- mixture 50/50 (V/V) : test article in a 0.2 % (W/W) suspension in sterile Codex liquid paraffin
+ Freund's complete adjuvant at 50 % (V/V) in an isotonic injectable solution, i.e. a final 0.1 % concentration of the test article.

Control group :
The intradermal injections and the topical occlusive application for 48 hours were carried out under the same conditions as in the treated group, sterile Codex liquid paraffin replacing the test article.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Treated group:
By intradermal route : 3 series of 2 x 0.1 ml injections
- Freund's complete adjuvant at 50 % (V/V) in an isotonic injectable solution.
- test article in a 0.1 % (W/W) solution in sterile Codex liquid paraffin.
- mixture 50/50 (V/V) : test article in a 0.2 % (W/W) suspension in sterile Codex liquid paraffin
+ Freund's complete adjuvant at 50 % (V/V) in an isotonic injectable solution, i.e. a final 0.1 % concentration of the test article.

Control group :
The intradermal injections and the topical occlusive application for 48 hours were carried out under the same conditions as in the treated group, sterile Codex liquid paraffin replacing the test article.
No. of animals per dose:
Treated group: 10 males and 10 females.
Control group: 5 males and 5 females
Details on study design:
PRELIMINARY STUDIES:

*Preliminary study for the induction:
- Group : at least one treated group of 2 males and 2 females per application.
- Application: (2 males and 2 females)1 injection of 0.1 ml per area and per animal of the test article (FAT 92267/A) in a 50, 25 or 10% (w/w) solution in sterile codex liquid paraffin.
- Application: (2 males and 2 females)1 injection of 0.1 ml per area and per animal of the test article (FAT 92267/A) in a 5, 1 or 0.1% (w/w) solution in sterile codex liquid paraffin.
-Application: 0.5 ml per area and per animal of the test article as supplied or in a 50% (w/w) solution in steril codex liquid paraffin.

*Preliminary study for the challenge exposure:
- Application: 0.5 ml per area and per animal of the test article as supplied or in a 50% (w/w) solution in sterile codex liquid paraffin.

MAIN STUDY
A. INDUCTION EXPOSURE
By intradermal route : 3 series of 2 x 0.1 ml injections
- Freund's complete adjuvant at 50 % (V/V) in an isotonic injectable solution ;
- test article in a 0.1 % (W/W) solution in sterile Codex liquid paraffin ;
- mixture 50/50 (V/V) : test article in a 0.2 % (W/W) suspension in sterile Codex liquid paraffin
+ Freund's complete adjuvant at 50 % (V/V) in an isotonic injectable solution, i.e. a final 0.1 % concentration of the test article.

By topical occlusive route for 48 hours, with 0.5 ml of the test article as supplied.

*Control group :
- The intradermal injections and the topical occlusive application for 48 hours were carried out under the same conditions as in the treated group,
sterile Codex liquid paraffin replacing the test article.


B. CHALLENGE EXPOSURE
- During the "challenge", topical occlusive application for 24 hours was performed in the treated group and in the control group with the test article as supplied and at the dose level of 0.5 ml (Maximum Non-Irritant Concentration : M.N.I.C). The vehicle was also applied during the challenge.

The cutaneous macroscopic examinations were performed according to the Magnusson & Kligman scale and to the challenge application sites, 24 and 48 hours after removal of the patches.
Positive control substance(s):
yes
Remarks:
Performed to prove the sensitivity of guinea pig strain, no data in the report.

Results and discussion

Positive control results:
No date in the report.

Any other information on results incl. tables

RESULTS:

No signs of systemic toxicity and no influence on body weights were noted.

Signs of irritation were noted during induction after application of the test article in the treated group.

The macroscopic and histopathologicai examinations revealed pathological lesions of delayed hypersensitivity in 17 out of the 20 treated animals.

No cutaneous abnormality was noted in the 9 guinea-pigs examined in the control group.

From the results obtained under the experimental conditions employed, the test article provoked a reaction of cutaneous sensitization in 85 % of the animals examined.

From the classification of Magnusson & Kligman, its sensitizing potentiol to the guineg-pig' skin is EXTREME (Grade V).

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Remarks:
Migrated information
Conclusions:
From the results obtained under the experimental conditions employed, the test article provoked a reaction of cutaneous sensitization in 85 % of the animals examined. FAT 92267/A is sensitizing to the guinea pig skin.
Executive summary:

The evaluation of the delayed cutaneous hypersensitivity of the test article was performed, according to the OECD Guideline 406 (Skin Sensitisation) and follwing GLP methodology, in the albino Hartley guinea-pig (supplier : Charles River France).

30 animals of both sexes were used , one control group of 10 animals (induction : vehicle - challenge : test article) and one treated group of 20 animals (induction and challenge : test article) were used.

- The applications corresponding to "induction" were performed as follows :

Treated group :

*By intradermal route : 3 series of 2 x 0.1 ml injections

- Freund's complete adjuvant at 50 % (V/V) in an isotonic injectable solution ;

- test article in a 0.1 % (W/W) solution in sterile Codex liquid paraffin ;

- mixture 50/50 (V/V) : test article in a 0.2 % (W/W) suspension in sterile Codex liquid paraffin

+ Freund's complete adjuvant at 50 % (V/V) in an isotonic injectable solution, i.e. a final 0.1 % concentration of the test article.

Injection of the test article in a 0.1 % solution provoked a weak to moderate irritation during the preliminary study.

*By topical occlusive route for 48 hours, with 0.5 ml of the test article as supplied.

As this application provoked a weak to moderate irritation during the preliminary study, no skin painting was performed on Day 8, with 0.5 ml of sodium lauryl sulphate at 10 % (W/W) in Codex paraffin.

Control group :

The intradermal injections and the topical occlusive application for 48 hours were carried out under the same conditions as in the treated group, sterile Codex liquid paraffin replacing the test article.

- The rest period was 11 days without treatment.

- During the "challenge", topical occlusive application for 24 hours was performed in the treated group and in the control group with the test article as supplied and at the dose level of 0.5 ml (Maximum Non-Irritant Concentration : M.N.I.C). The vehicle was also applied during the challenge.

The cutaneous macroscopic examinations were performed according to the Magnusson & Kligman scale and to the challenge application sites, 24 and 48 hours after removal of the patches.

Histopathologicai examinations of the skin were performed for 4 animals of the treated group which showed doubtful macroscopic reactions at 24 hours.

RESULTS AND CONCLUSION:

- No signs of systemic toxicity and no influence on body weights were noted.

- Signs of irritation were noted during induction after application of the test article in the treated group.

- The macroscopic and histopathologicai examinations revealed pathological lesions of delayed hypersensitivity in 17 out of the 20 treated animals. No cutaneous abnormality was noted in the 9 guinea-pigs examined in the control group.

From the results obtained under the experimental conditions employed, the test article provoked a reaction of cutaneous sensitization in 85 % of the animals examined. FAT 92267/A is sensitizing to the guinea pig skin.