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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 5, 1988 - May 19, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1981
Qualifier:
according to
Guideline:
other: Magnusson and Kligman (J. invest. Dermatol. 52, 268-276, 1969, Cont. Dermatitis 6, 46-50, 1980),
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Several valid guinea pig studies are available, no further information from an LLNA is required.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: liquid, insoluble in water
- Storage condition of test material: room temperature
In addition to the test compound, the following leather samples were used in the challenge reactions:
B = blind sample
C = treated sample, compounds solubilized in buthylacetate
D = treated sample, compounds solubilized in a nitrolacquer
Specific details on test material used for the study:
In addition to the neat test material, leather patches treated with the test material were used in addition for challenge reactions.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 331 to 424 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: ad libitum standard guinea pig pellets - NAFAG No. 846, Gossau SG
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: seame oil
Concentration / amount:
1%
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
30%
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
10%
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 male and 10 females per group
Details on study design:
RANGE FINDING TESTS:
The concentrations of the test article for the induction and challenge periods were determined on separate animals.

MAIN STUDY
A. INDUCTION EXPOSURE
The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites. Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows: adjuvant and saline (1:1), test compound in sesame oil, test compound in the adjuvant saline mixture. Concentration of test compound in sesame oil and adjuvant mixture: 1 %. One week later the test compound was incorporated in vaseline and applied on a filterpaper patch to the neck of the animals (patch 2 x 4 cm; occluded administration for 48 hours). Dose of application: approx. 0.4 g paste of 30 % test compound in vaseline.

B. CHALLENGE EXPOSURE
First challenge: two weeks after the epidermal induction application the animals were tested on the flank with test compound in vaseline and with the blind leather patch sample B (patch 2 x 2 cm; occluded administration for 24 hours). Dose of application: approx. 0.2 g paste of 10 % test compound in vaseline.
Second Challenge: After a further rest period of 10 days, a second challenge application was performed. The animals were treated on the contralateral flanks with one patch of the treated leather fabrics C and D. Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings.

CONTROL GROUP
A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the neat test compound (at least 10 animals) to control the maximum subirritant concentration of the test article in adjuvant treated animals. Separate animals were treated with test compound and the leather samples to control the primary irritant effects. On account of experience from other experiments 3% and 10% test compound were tested in vaseline. No erythema reactions were induced with both concentrations. Therefore 10 % was used as the maximum subirritant concentration for the challenge application with the test compound.

Results and discussion

Positive control results:
The sensitivity of the strain is checked every six months with Paraphenylene-diamine or Potassium-diehromate.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
14
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
14
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
all leather samples
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
all leather samples
No. with + reactions:
0
Total no. in group:
20

Any other information on results incl. tables

Under the experimental conditions employed, 14 animals of the test group reacted to the neat product 24 and 48 hours after removing the dressing . No reactions were elicited with the treated leather samples.

Applicant's summary and conclusion

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
70% of the animals were sensitized by the test compound under the experimental conditions employed. But none of the animals reacted to the challenge application of leather patches treated with the test compound. According to the maximization grading the neat test compound showed a strong grade of skin-sensitizing (contact allergenic) potential in albino guinea pigs.