Registration Dossier

Administrative data

Description of key information

skin sensitisation (m/f), 30% challenge, not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
LLNA not available as test method at the time of testing
Species:
guinea pig
Sex:
male/female
Details on test animals and environmental conditions:
The test was performed on 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group, respectively, initially weighing between 330 to 390 g. The animals were housed i n d i v i d u a l l y 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, kept at a constant room temperature of 22+/- 3°C, at a r e l a t i v e humidity of 30 to 70% and a 12 hours light cycle day.The animals received ad libitum standard guinea pig pellets -NAFAG No. 845, Gossau SG and fresh water. All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer. Analytical results are available at the animal supply office. The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesserschutz) are available to CIBA-GEIGY Limited, as well as the results of inhouse chemical analysis by the analytical laboratories of the Pharmaceutical Division, CIBA-GEIGY Limited.
Route:
intradermal and epicutaneous
Vehicle:
other: vaseline
Concentration / amount:
Intradermal induction: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 pre-test-adjuvant/saline mixture 1:1 (v/v)-5% of test item in physiological saline (w/v)-5% of test item in the adjuvant/saline mixture (w/v)The intradermal induction was administered into the neck regionEpirdermal induction:The concentrations of the epidermal applications were selected on account of the primary irritation potential of the test item. The following concentrations have been examined on separate animals for the determination o the maximum sub-irritant concentration: 10, 20, 30 and 50% in vaseline.Erythema reactions were observed with 50% of the test item in vaseline. 50% of the test item in vaseline applied on a filter paper patch to neck of the animals (patch 2x4 cm, ca. 0.4 g paste per patch, occluded administration for 48h)Challenge 30% of the etst item in vaseline applied on the flank (on a patch 2x2 cm, ca. 0.2g paste per patch, occluded administration for 24h) and vaseline alone
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
Intradermal induction: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 pre-test-adjuvant/saline mixture 1:1 (v/v)-5% of test item in physiological saline (w/v)-5% of test item in the adjuvant/saline mixture (w/v)The intradermal induction was administered into the neck regionEpirdermal induction:The concentrations of the epidermal applications were selected on account of the primary irritation potential of the test item. The following concentrations have been examined on separate animals for the determination o the maximum sub-irritant concentration: 10, 20, 30 and 50% in vaseline.Erythema reactions were observed with 50% of the test item in vaseline. 50% of the test item in vaseline applied on a filter paper patch to neck of the animals (patch 2x4 cm, ca. 0.4 g paste per patch, occluded administration for 48h)Challenge 30% of the etst item in vaseline applied on the flank (on a patch 2x2 cm, ca. 0.2g paste per patch, occluded administration for 24h) and vaseline alone
Details on study design:
The induction stage was performed in 2 weeks ( first week intradermal, second week epicutaneous). During weeks 3 and 4 no treatments were performed. At week 5 the challenge exposure was performed.Induction reactionsAfter the intradermal and the epidermal induction application irritant reactions are normally induced by the adjuvant and the high test article concentration. Because most of the reactions are treatment related and not compound related, the reactions are only described in special cases in the section of results. Twenty four and forty eight hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale (Appendix 1)The body weight was recorded at start and end of the test.
Challenge controls:
A control group of 10 animals (5 m/5 f) 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 article to check the maximum subirritant concentration of the test article in adjuvant treated animals.
Positive control substance(s):
yes
Remarks:
potassium dichromate
Positive control results:
90% of animals at 24 and 48h
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30%. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30%. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
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: test group. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
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: test group. Dose level: 0. No with. + reactions: 0.0. 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:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
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: other: control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other:
Dose level:
30%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control. Dose level: 30%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control
Dose level:
30%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: control. Dose level: 30%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
n.a.
No. with + reactions:
9
Total no. in group:
10

No erythema nor oedhema were recorded for the test group animals.

No test item related effect on the body weight of the animals was observed.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
The test item was tested for skin sensitisation following OECD 406. Under the experimental conditions the test item does not show skin sensitising properties.
Executive summary:

The test item was tested for skin sensitisation following OECD 406. Guine pigs (10 males and 10 females) were tested with intradermal and epicutaneous occlusive induction at 50% of the test item (with adjuvant for the intradermal test, vaseline for the epicutaneous) in the first two weeks. At week 5 the challenge step was performed with an occlusive patch at 30% of the test item. Skin irritation was recorded, together with animals weight.

Under the experimental condition 5% at 24h after patch removal and 10% of the animals at 48h showed positive reactions.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The analogue test item was tested for skin sensitisation following OECD 406 (Huntsman, 1993). The test item is a mixture of different substances that are closely related by a structural point of view. Under the experimental conditions the test item did not show any skin sensitizing potential.

Based on the read across considerations the same resutls can be applied to Acid Black 107:1


Justification for classification or non-classification

Under Regulation 1272/2008 a substance is classified as skin sensitizer category 2 if, in a GPMT over the tested animals ≥ 30 % to < 60 % responding at > 0,1 % to ≤ 1 % intradermal induction dose or ≥ 30 % responding at > 1 % intradermal induction dose.

The intradermal induction dose wa at 4% and the percentage responding is 10% at 48h, therefore the substance is not classified as skin sensitizer.