Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From September 26th to December 1th, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test conducted according to internationally accepted testing guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

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:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Validity: May, 1999
- Storage conditions: room temperature

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
- Weight at study initiation: 301-421 g
- Housing: individually in Macrolon cages (type 3) randomly
- Diet (e.g. ad libitum): ad libitum standard guinea pig pellets -NAFAG No. 845, Gossau SG
All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer.
- Water (e.g. ad libitum): fresh water
The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972).
- Acclimation period: from 21th of September 1994
- Sensitivity of the strain: checked once or twice a year with a known mild to moderate sensitiser, such as mercaptobsnzothiazole, hexyl cinnamic aldehyde or potassiumdichromate.

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: intradermal injection and epidermal application
Vehicle:
physiological saline
Concentration / amount:
INTRADERMAL INJECTION: 5 % in physiological saline (w/v).
EPIDERMAL APPLICATION: 30 and 50 % in physiological saline
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
INTRADERMAL INJECTION: 5 % in physiological saline (w/v).
EPIDERMAL APPLICATION: 30 and 50 % in physiological saline
No. of animals per dose:
INTRADERMAL APPLICATION
Three pairs of intradermal injections (0.1 ml per injection):
- adjuvant/saline mixture 1:1 (v/v)
- 5 % FAT 21070/B in physiological saline (w/v)
- 5 % FAT 21070/B in the adjuvant/saline mixture (w/v)

EPIDERMAL APPLICATION
The application site of all animals was pretreated with 10 % sodium-laurylsulfate (open application)
- 50 % FAT 21070/B in physiological saline

CHALLENGE
- 30 % FAT 21070/B in physiological saline
Details on study design:
RANGE FINDING TESTS:
The test started with the minimum number of animals (5 per sex for the test group and 5 of one sex for controls). After the challenge procedure, it was
not possible to conclude if the test substance is a sensitiser or not and therefore testing in additional animals was performed to give a total of 20 test and 10 controlanimals.

MAIN STUDY
A. INDUCTION EXPOSURE: INTRADERMAL INJECTION
- No. of exposures: 3 pairs
- Control group: adjuvant/saline mixture and physiological saline
- Site: left and right side of the shaved neck
- Frequency of applications: three simultaneously

A. INDUCTION EXPOSURE: EPIDERMAL APPLICATION
- No. of exposures: 6 animals
The application site of all animals was pretreated with 10% sodium-laurylsulfate (open application)
- Type of application: on a filterpaper patch patch 2x4 cm; 0,4 g per patch; occluded administration;
- Site: the neck of the animals
- Duration: 48 h
- Control group: a physiological saline only

B. CHALLENGE EXPOSURE
- No. of exposures: 6 animals
- Type of application: flank in physiological saline; 2x2 cm patch; 0.2 g per patch
- Site: the neck of the animals
- Duration: 24 h
- Control group: a physiological saline only

Results and discussion

Positive control results:
Number of positive animals per group after occlusive epidermal application : 0 (24 and 48 hours)

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
after occlusive epidermal application
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: after occlusive epidermal application. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
after occlusive epidermal application
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: after occlusive epidermal application. No with. + reactions: 3.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group- vehicle control
Dose level:
epidermal application-removal of dressing
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
DRAIZE score= erythema; edema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control group- vehicle control. Dose level: epidermal application-removal of dressing. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: DRAIZE score= erythema; edema.
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group- test article control
Dose level:
epidermal application-removal of dressing
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
DRAIZE score= erythema; edema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control group- test article control. Dose level: epidermal application-removal of dressing. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: DRAIZE score= erythema; edema.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group-vehicle control
Dose level:
epidermal application-removal of dressing
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
DRAIZE score= erythema; edema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: control group-vehicle control. Dose level: epidermal application-removal of dressing. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: DRAIZE score= erythema; edema.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group- test article control
Dose level:
epidermal application-removal of dressing
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
DRAIZE score= erythema; edema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: control group- test article control. Dose level: epidermal application-removal of dressing. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: DRAIZE score= erythema; edema.
Reading:
1st reading
Hours after challenge:
24
Group:
other: test group-vehicle control
Dose level:
epidermal application-removal of dressing
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
DRAIZE score=erythema; edema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test group-vehicle control. Dose level: epidermal application-removal of dressing. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: DRAIZE score=erythema; edema.
Reading:
1st reading
Hours after challenge:
24
Group:
other: test group- vehicle control
Dose level:
epidermal application-removal of the dressing
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
DRAIZE score=erythema; edema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test group- vehicle control. Dose level: epidermal application-removal of the dressing. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: DRAIZE score=erythema; edema.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test group-vehicle control
Dose level:
epidermal application-removal of the dressing
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
DRAIZE score=erythema; edema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test group-vehicle control. Dose level: epidermal application-removal of the dressing. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: DRAIZE score=erythema; edema.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test group-test article
Dose level:
epidermal application-removal of the dressing
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
DRAIZE score=erythema; edema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test group-test article. Dose level: epidermal application-removal of the dressing. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: DRAIZE score=erythema; edema.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
30% intradermal injections of an adjuvant/saline mixture 1:1 (v/v; 0.1 ml per injection)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
erithema, edema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30% intradermal injections of an adjuvant/saline mixture 1:1 (v/v; 0.1 ml per injection). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: erithema, edema.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% intradermal injections of an adjuvant/saline mixture 1:1 (v/v; 0.1 ml per injection)
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
erythema, edema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% intradermal injections of an adjuvant/saline mixture 1:1 (v/v; 0.1 ml per injection). No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: erythema, edema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
30% intradermal injections of an adjuvant/saline mixture 1:1 (v/v; 0.1 ml per injection)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
erythema;edema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30% intradermal injections of an adjuvant/saline mixture 1:1 (v/v; 0.1 ml per injection). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: erythema;edema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% intradermal injections of an adjuvant/saline mixture 1:1 (v/v; 0.1 ml per injection)
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
edema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% intradermal injections of an adjuvant/saline mixture 1:1 (v/v; 0.1 ml per injection). No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: edema.

Any other information on results incl. tables

After removal of the dressing on day 10, irritation of the epidermal application site was observed in 10/10 control and in 20/20 test group animals.

Body weights were not affected by treatment.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information According to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions employed, 10 % and 15 % of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings, respectively.
Executive summary:
The determination of the sensitizing potential was determined by a Maximixation test, according to OECD 406 guideline and GLP. The reaction on the test substance was observed in Guinea Pigs for 48 hours. Induction reactions, challenge reactions and changes in body weight were observed. Under the experimental conditions employed, 10 % and 15 % of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings, respectively. The test shows low reactions to the test item, up to 15% of positive reaction. Body weights were not affected by treatment.