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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
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test was not valid at time of test conduct

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production,4332 Stein / Switzerland
- Weight at study initiation: between 312 to 412 g
- Housing: The animal s were housed individually in Macrolon cages (Type 3), assigned to the different groups by means of random numbers generated by the random number generator, identified by individual ear tags
- Diet (e.g. ad libitum): ad libitum standard guinea pig pellets - NAFAG No. 845, Gossau SG
- Water (e.g. ad libitum): ad libitum, fresh water
- Acclimation period: November 19, 1992

ENVIRONMENTAL CONDITIONS
- Temperature (°C):2 2+-3
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
The concentration for the intradermal injections was selected on account of the solubility of the test article in standard vehicles and its local and systemic tolerability in a pretest.
The following concentrations of test article have been prepared for intradermal injection: 5 % in physiological saline.
Since 5% FAT 41001/F in physiological saline could be injected and was well tolerated, this concentration was used for the intradermal induction.
- 5% FAT 41001/F in physiological saline (w/v)
- 5% FAT 41001/F in the adjuvant/saline mixture (w/v)
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
The concentrations for the epidermal applications were selected on account of the primary irritation potential of the test article. The following concentrations have been examined on separate animals for the determination of the maximum sub irritant concentration :
10, 20, 30, and 50% in Vaseline.
The tested concentrations did not induce erythema reactions, therefore the following concentration was selected:
Epidermal induction
Concentration of test article: 50%
Vehicle: Vaseline
No skin irritation was observed in the pretest. Therefore the application site was pretreated with 10% sodium-lauryl sulfate (open application) 24 hours prior to the epidermal induction application.
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
The concentrations for the epidermal applications were selected on account of the primary irritation potential of the test article. The following concentrations have been examined on separate animals for the determination of the maximum sub irritant concentration: 10, 20, 30, and 50% in Vaseline.
The tested concentrations did not induce erythema reactions, therefore the following concentration was selected for epidermal challenge:
Concentration of test article: 50%
Vehicle: Vaseline

Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Test groups: 10 male and 10 female
Control groups: 5 males and 5 females
Details on study design:
Test procedure

Induction procedure (weeks 1 and 2):
The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.
First induction week, intradermal injection
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
- adjuvant/saline mixture 1:1 (v/v)
- test article FAT 41001/F in physiological saline (w/v)
- test article FAT 41001/F in the adjuvant/saline mixture (w/v)
Second induction week, epidermal application
In the second week of induction FAT 41001/F was incorporated in Vaseline (w/w) and applied on a filter paper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g paste per patch; occluded administration for 48 hours).
Rest period
During weeks 3 and 4 no treatments were performed.
Challenge (week 5)
The animals were teste d on the flank with FAT 41001/F in Vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours).
Control group
A control l group of 10 animals (5 m/5 f) was treated d 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 test t article e to check the maximum sub irritant concentration of the test article e in adjuvant treated animals.
Positive control substance(s):
yes
Remarks:
potassium dichromate

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
1%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The test substance is classified as skin sensitiser in albino guinea pigs according to the grading of Magnusson and Kligman.
Executive summary:

A sensitisation test in albino guinea pigs was performed to determine the contact allergenic potency of FAT 41001/F in albino guinea pigs . This test was based on the OECD Guideline No. 406, adopted May 12, 1981, adapted July 17, 1992, by the OECD council

100 and 90 % of the animals were sensitised by the test subsance under the experimental conditions employed.

According to the maximisation grading the test substance showed skin-sensitising (contact allergenic ) effects in albino guinea pigs .