Registration Dossier

Administrative data

Description of key information

A guinea pig maximization assay according OECD guideline 406 was performed to assess the skin senitization potential of the substance. Injection of the test item caused slight irritation, a sensitization reaction was not observed. In addition, a mixture containing the test item was examined in a human patch test with 200 volunteers. Sensitization was not recorded, skin changes were also not observed. The substance is therefore not considered to be a skin sensitizer.

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:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
yes
Remarks:
no data concerning test substance, no positive control data
Principles of method if other than guideline:
B. Magnusson and A.M. Kligman (1970) in "Allergic Contact Dermatitis in the Guinea Pig - Identification of Contact Allergens", (C.C. Thomas, Springfield, Illinois, U.S.A.) and by G. Klecak in "Advances in Modern Toxicology", Vol. 4 (Francis N. Marzulli and Howard I. Maibach, Hemisphere Publishing Corporation, Washington, U.S.A., 1977).
GLP compliance:
not specified
Remarks:
Internal Quality assurance signature page included.
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA is not required since adequate data from a guinea pig maximization study are available.
Species:
guinea pig
Strain:
other: albino
Sex:
female
Route:
intradermal
Vehicle:
paraffin oil
Concentration / amount:
5%
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
50%
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
50%
No. of animals per dose:
20
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
An area of dorsal skin 4x6 cm in the scapular region was clipped free of hair with an electric clipper. Three pairs of intradermal injections were given simultaneously into this area. Each dose was 0.05 mL.
Preparation of injection were made as follows:
1. Freund's complete adjuvant was diluted 1:1 with water for injection.
2. 5% test article in paraffin oil (w/v) (for control group only paraffin oil was used)
3. Freund's complete adjuvant diluted 1:1 with water for injection 0.04 mL and 5% test article in paraffin oil (w/v) 0.02 mL. Freund's complete adjuvant diluted 1:1 with water for injection and the test article was imcompatible. Therefore two injections were given separately on top of each other. (For control group Freund's adjuvant, water for injection and paraffin oil 1:1:1 was used)
Six days after the injections, the same 4x6 cm scapular area was clipped free of hair. To provoke a mild inflammatory reaction 10% sodium laurylsulphate was massaged into the skin with a glass rod. 24 hours later 0.4 g of the test article saturated with 0.4 g paraffin oil was spread over a 3x5 cm patch of Whatman No. 3 MM paper. The patch was placed on the skin and covered with 7 cm impermeable plastic adhesive tape. This was firmly secured by an elastic adhesive bandage wound around the trunk. The dressing was left in place for 48 hours. For the control group only paraffin oil was used.

B. CHALLENGE EXPOSURE
The guinea pigs were challenged topically three weeks after the intradermal induction period using undiluted test article and paraffin oil.
Hair was removed with electric clipper from a 5x5 cm area on the left and right flank on each guinea pig. 0.1 g test article saturated with 0.1 g paraffin oil was applied to a 2x2 cm Whatman No. 3 paper in a fashion similar to that used for topical application and placed on the left flank of the test and on the right flank of the control group. On the right flank of the test group a similar patch with 0.1 mL paraffin oil was placed.
The patches were sealed to the flank for 24 hours under a 4 cm strip of "Blenderm" secured by "Scanpor Tape" wound around the trunk.
Each challenge site was evaluated 24, 48 and 72 hours after removal of the patch. Observation of the sites was aided by clipping away the hair and cleaning with water three hours before evaluation.
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20

Intradermal injections of Freund's complete adjuvant, both alone and mixed with the test article, elicited irritation. A slight dermal irritation was observed following intradermal injections of the test article, 5% in paraffin oil.

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A guinea pig maximization assay according OECD guideline 406 was performed to assess the skin senitization potential of the substance. For induction the material was dissolved in paraffin oil and administered intradermally at 5% and topical at 50% onto dorsal skin. The challenge reaction was performed by epicutaneous application of a 50% solution. A positive control was not performed. Injection of the test item caused slight irritation, a sensitization reaction was not observed. In addition, a mixture containing the test item was examined in a human patch test with 200 volunteers (2 -65 years old, 33% men, 66% woman) representing the general population. The material was administered onto skin as a 4% solution for 2 days during 5 weeks under occlusive conditions. Two weeks after the last induction, a challenge reaction was provoked by topical application of the mixture for 48h. Sensitization was not recorded, any skin changes were also not observed. In conclusion, repeated administration of the test material to animals or humans did not induce an allergic reaction. The substance is therefore not considered to be a skin sensitizer.

Justification for classification or non-classification

Classification, Labeling, 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.