Registration Dossier

Administrative data

Description of key information

The substance did not cause skin sensitization in guinea pigs as tested in a GLP compliant study following OECD testing guideline 406.

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
Study period:
April 11,1989 - May 12, 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
yes
Remarks:
(in housing conditions (temperature)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1984
Deviations:
yes
Remarks:
(in housing conditions (temperature)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1989 when the guinea pig maximisation test was an accepted and recommendet method to assess skin sensitization potential. The GPMT is valid and sufficient, no further animal study is necessary.
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
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, 4332 Stein, Switzerland
- Age at study initiation: approx. 10 wks
- Weight at study initiation: 381-467 g
- Housing: individually in Macrolon cages (type 3)
- Diet: standard guinea pig pellets (NAFAG No. 845, Gossau SG); ad libitum
- Water: ad libitum
- Acclimation period: 8 d
All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
other: sesame oil
Concentration / amount:
1 %
Day(s)/duration:
day 1
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
30 % in vaseline
Day(s)/duration:
1 wk after intradermal induction / 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
10 %
Day(s)/duration:
2 wks after epicuatneous induction / 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Number of animals in test group: 20
Number of animals in negative control group: 20
Details on study design:
RANGE FINDING TESTS:
The following concentrations were examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration of the test article: 10 and 30 % in vaseline.
Results:the concentration (1 %) for the intradermal injections was selected on account of the solubility of the test article in standard vehicles.
Erythema reactions were observed with 30% in vaseline. 30 % was, therefore, selected for the epidermal induction application and 10 % as maximum subirritant concentration for the epidermal challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE (intradermal)
- Test substance group: (cranial) Freund's complete adjuvant (FCA) 1 + 1 (v/v) blended with saline
- Test substance group: (middle) test article in vehicle
- Test substance group: (caudal) test article in Freund's complete adjuvant (FCA)/saline-mixture
- Control group (cranial): Freund's complete adjuvant (FCA) 1 + 1 (v/v) blended with saline
- Control group (middle): vehicle
- Control group (caudal): Freund's complete adjuvant (FCA)/saline-mixture
- Site: interscapular region (2x4 cm)
- Concentrations: 1 %
- Vehicle: sesame oil
- Volume per injection: 0.1 mL
- Evaluation (hr after injection): no data

Epicutaneous induction exposure
- Time schedule: 1 wks after intradermal injection.
- Site: same as intradermal injection
- Method of test substance application: on 2 x 4 cm test patches
- Type of coverage: occlusive
- Concentration: 30 % test article
- Vehicle: vaseline
- Amount applied: approx. 0.4 g per patch
- Duration: 48 h
- Evaluation: (hr after challenge): no data

B. CHALLENGE EXPOSURE
- Time schedule: 2 wks after the epidermal induction application
- Site: one flank (test substance and vehicle), other flank (vehicle alone)
- Area of application: 2 x 2 cm
- Concentration: 10 %
- Vehicle: vaseline
- Amount applied: approx. 0.2 g per patch
- Duration: 24 h
- Evaluation (hr after challenge): 24 and 48 hours after termination of exposure according to Draize Scoring Scale
Positive control substance(s):
yes
Remarks:
The sensitivity of the strain is checked every six months with Paraphenylene-diamine or Potassium-dichromate.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20

animal weights (g):

males, control group:(at start) 431 ± 18.2; (at end) 674.7 ± 38.0

males, test group: (at start) 430.4 ± 27.0; (at end) 673.8 ± 35.5

females, control group:(at start) 430.1 ± 30.5; (at end) 573.7 ± 43.2

females, test group: (at start) 417.4 ± 20.4; (at end) 552.7 ± 39.1

Local effects (skin) were not documented.

Interpretation of results:
GHS criteria not met
Conclusions:
No animal of the test group was sensitised by the test item under the experimental condition employed.
Executive summary:

A GLP-compliant guinea pig maximization test was performed following OECD guideline 406. The test was performed on 10 male and 10 female guinea pigs per group. During induction, 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 article (1%) in sesame oil; test article (1%) in the adjuvant saline mixture. One week later the test item was incorporated in vaseline (30%) and applied on a filterpaper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g paste per patch; occluded administration for 4 8 hours). Two weeks after the epidermal induction application the animals were tested on the flank with the test item in vaseline (10%) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours). 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 article (at least 10 animals) to control the maximum subirritant concentration of the test article in adjuvant treated animals. Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. Under the experimental conditions employed, none of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings.

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

Guinea Pig Maximisation Test

In the key dermal sensitization study, the test article in sesame oil for intradermal induction and in vaseline for epidermal treatments, was tested in approx. 10 weeks old Pirbright White Strain guinea pigs (10/sex) using the guinea pig maximisation test (OECD 406; EU-Method B.6). Reactions were graded according to the Draize scoring scale 24 and 48 h after challenge. No mortality or clinical signs occurred during the observation period (ca. 23 days). The positive control substances (paraphenylene-diamine or potassium-dichromate) induced the appropriate responses. In this study, the test article is not a dermal sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218.