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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted according to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Details on test material:
- Physical state: solid
- Purity: commercial grade
- Stability under test conditions: In the report it was stated that stability was guaranteed by the sponsor.
- Storage condition of test material: room temperature

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: CIBA-GEIGY LTD. Tierfarm, Sisseln, Switzerland
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 304 - 461 g
- Housing: individually in Macrolon type-3 cages.
- Diet (ad libitum): standard guinea pig pellets, NAFAG No. 846
- Water (ad libitum): fresh water
- Acclimation period: 9 days

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: For intradermal treatment sesame oil and for epidermal treatment vaseline was used as vehicle.
Concentration / amount:
Intradermal induction was performed with 1 % dilution of test article in sesame oil or in adjuvant/physiological saline. A 1:1 mixture of adjuvant and saline served as control.
Epidermal induction was conducted with 10 % test article in vaseline as a paste of 0.4 g.
The challenge was performed with 0.3 % test article in vaseline as paste of 0.2 g.


Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: For intradermal treatment sesame oil and for epidermal treatment vaseline was used as vehicle.
Concentration / amount:
Intradermal induction was performed with 1 % dilution of test article in sesame oil or in adjuvant/physiological saline. A 1:1 mixture of adjuvant and saline served as control.
Epidermal induction was conducted with 10 % test article in vaseline as a paste of 0.4 g.
The challenge was performed with 0.3 % test article in vaseline as paste of 0.2 g.


No. of animals per dose:
20 animals (10 males, 10 females)
Details on study design:
RANGE FINDING TESTS
The concentration of the test compound for the induction and challenge periods were determined on four separate animals with concentrations of 0.3 %, 1 %, 3 %, 10 %. No further details are given.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2; one intradermal injection (0.1 ml/site) of 1 % dilution in sesame oil and one epidermal application of 10 % dilution in vaseline one week after intradermal injection under occlusive conditions.
- Exposure period: Epidermal application was performed for 48 h.
- Site: neck

B. CHALLENGE EXPOSURE (TWO WEEKS AFTER INDUCTION)
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 h
- Site: flank
- Concentrations: 0.3 % test article in vaseline
- Evaluation (hr after challenge): approximately 24 and 48 hours after challenge

SCORING
Evaluation of skin reactions according to Draize (1959)

Erythema and eschar formation
- No erythema 0
- Very slight erythema (barely perceptible) 1
- Well defined erythema 2
- Moderate to severe erythema 3
- Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Edema formation
- No edema 0
- Very slight edema (barely perceptible) 1
- Slight edema (edges of area well defined by definite raising) 2
- Moderate edema (raised approximately 1 mm) 3
- Severe edema (raised more than 1 mm and extending beyond area of exposure) 4
Challenge controls:
During the induction period a control group was treated with adjuvant and the vehicle. One half of this group was challenged with vehicle and the other half with test article.
Positive control substance(s):
yes
Remarks:
The sensitivity of the strain is checked every six months with paraphenylene-diamine or potassium-dichromate according to Maurer and Hess 1994 (Toxicology 31, 217-222) in the testing facility.

Results and discussion

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
Clinical observations:
no skin irritations were observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no skin irritations were observed .
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no skin irritations were observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no skin irritations were observed.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no skin irritations were observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.3 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no skin irritations were observed .
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.3 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no skin irritations were observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.3 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no skin irritations were observed .

Applicant's summary and conclusion