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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:
guideline study
Remarks:
non GLP test

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study has been performed in 1986 following the standards valid at that time

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): FAT 40'224/B
- Contents of active ingredients: a.i:80%
- Physical properties: powder; solubility in water >100g/L; pH: 6,5(lg/L water)
- Lot/batch No.: TZ 2382/8
- Validity: May 1987

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
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 old
- Weight at study initiation: 305 to 416 g
- Housing: The animals were housed individually in Macrolon cages (Type3).
- Diet (e.g. ad libitum): The animals received ad libitum standard guinea pig pellets - NAFAG No.846, Gossau SG.
- Water (e.g. ad libitum): Fresh water, ad libitum
- Acclimation period: 9 days

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal: NaCl; epicutaneous: vaseline
Concentration / amount:
First Induction intradermal application:
Concentration of FAT 40224/B in NaCl and adjuvant mixture: 1 %.

Second Induction, epidermal application:
Dose of application: approx. 0.4 g paste of 30 % FAT 40224/B in vaseline

Challenge
Dose of application : approx. 0.2 g paste of 10 % FAT 40224/B in vaseline.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: intradermal: NaCl; epicutaneous: vaseline
Concentration / amount:
First Induction intradermal application:
Concentration of FAT 40224/B in NaCl and adjuvant mixture: 1 %.

Second Induction, epidermal application:
Dose of application: approx. 0.4 g paste of 30 % FAT 40224/B in vaseline

Challenge
Dose of application : approx. 0.2 g paste of 10 % FAT 40224/B in vaseline.
No. of animals per dose:
10/sex/dose
Details on study design:
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 one week later.
First Induction intradermal application:
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 FAT 40224/B in NaCl
- test compound FAT 40224/B in the adjuvant saline mixture
Concentration of FAT 40224/B in NaCl and adjuvant mixture: 1 %.

Second Induction, epidermal application
One week later FAT 40224/B was incorporated in vaseline and applied on a filter paper patch to the neck of the animals (patch 2 x 4 cm; occluded administration for 48 hours). The application sites were pretreated the day before with 10 % sodium lauryl sulfate (open application). Dose of application: approx. 0.4 g paste of 30 % FAT 40224/B in vaseline

B. CHALLENGE EXPOSURE
Two weeks after the epidermal induction application the animals were tested on the flank with FAT 40224/B in vaseline and the vehicle alone (patch 2 x 2 cm; occluded administration for 24 hours). Dose of application: approx. 0.2 g paste of 10 % FAT 40224/B in vaseline. The concentration of the test compound for the induction and challenge periods were determined on separate animals.

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 test compound (at least 10 animals) to control the maximal subirritant concentration of the test compound in adjuvant treated
animals.

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. The sensitizing potential of FAT 40224/B was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.

Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
17
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 17.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
17
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 17.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
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.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
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.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the maximization grading the test substance showed an extreme grade of skin-sensitizing (contact allergenic) potential in albino guinea pigs.
Executive summary:

In a skin sensitization study, performed according to OECD guideline 406, Pirbright White strain guinea pigs were treated with test substance. The test was performed on 10 male and 10 female animals per group. The induction was a two-stage operation. For the first induction three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows: 1) adjuvant and saline (1:1), 2) test substance in NaCl, 3) test substance in the adjuvant saline mixture. The concentration of test substance in NaCl and adjuvant mixture was 1 %. Second induction was performed one week later by epidermal application over the injection sites. The test substance was incorporated in vaseline and applied on a filter paper patch to the neck of the animals (occluded administration for 48 hours). The application sites were pretreated the day before with 10 % sodium lauryl sulfate (open application). Dose of application was approx. 0.4 g paste of 30 % test substance in vaseline. Two weeks after the epidermal induction application the animals were tested on the flank with test substance in vaseline and the vehicle alone (occluded administration for 24 hours), approx. 0.2 g paste of 10 % test substance in vaseline. 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 test compound (at least 10 animals). Twenty four hours and 48 hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. Under the experimental conditions employed, 85 % of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings. The test substance is, therefore, classified as an extreme sensitizer in albino guinea pigs according to the grading of Magnusson and Kligman.