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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:
weight of evidence
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Murine Local Lymph Node Assay (LLNA) is the first-choice method for in vivo testing according to the REACH Regulation. However, this test was performed before entry into force of the REACH Regulation.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Jeffcat DMP
Specific details on test material used for the study:
- Name of test material (as cited in study report): 1,4-Dimethylpiperazin
- Physical state: liquid, slight yellowish
- Analytical purity: 99.7 %
- Lot/batch No.: 32-1659
- Storage condition of test material: room temperature, exclusion of oxygen (stored under nitrogen)

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White, Dunkin Hartley Cr1: (HA)BR [SPF]
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River GmbH - Wiga, Kisslegg, FRG
- Age at study initiation: Young adult animals
- Weight at study initiation: 348 - 396 g
- Housing: 5 per cage
- Diet (ad libitumn): Kliba Labordiaet 341 (Kaninchen-Meerschweinchen-Haltungsdiaet)
- Water (ad libitum): tap water; about 2 g of ascorbic acid per 10 L water was added to the drinking water twice a week
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction: test substance 0.5% in 0.9% aqueous NaCl-solution
Percutaneous induction: test substance 10% in aqua bidest.
Challenge: test substance 2% in aqua bidest.
Challenge
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction: test substance 0.5% in 0.9% aqueous NaCl-solution
Percutaneous induction: test substance 10% in aqua bidest.
Challenge: test substance 2% in aqua bidest.
No. of animals per dose:
Test groups: 10
Control groups: 5
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6 intradermal injections in groups of two per animal ((A) front row: 2 injections each of 0.1 ml Freund's adjuvant* without test substance emulsified with 0.9% aqueous NaCl-solution in a ratio of 1 : 1 (B) middle row: 2 injections each of 0.1 ml of the test substance formulation
(C) back row: 2 injections each of 0.1 ml Freund's adjuvant / 0.9% aqueous NaC1-solution (1 : 1) with test substance) and one percutaneous exposure 1 week after intradermal induction.
- Exposure period: percutaneous exposure: 48 h
- Test groups: 10 animals
- Control group: 5 animals
- Site: shoulder, same area as in the case of the previous intradermal application

B. CHALLENGE EXPOSURE
- No. of exposures: single percutaneous exposure
- Day(s) of challenge: 24 h
- Site: intact flank
- Concentrations: 2 x 2 cm filter paper strips containing the test substance.
- Evaluation (hr after challenge): 24 and 48 h after removal of the patch.

Positive control substance(s):
yes
Remarks:
Performed in a separate study twice a year in the laboratory with alpha-hexylcinnamaldehyde.

Results and discussion

Positive control results:
A positive control (reliability check) with a known sensitizer is not included in this study. However, a seperate study is performed twice a year in the laboratory. The positive control with Alpha-Hexylcinnamaldehyde techn. 85% showed that the test system was able to detect sensitizing compounds under the laboratory conditions shown.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2 %
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
2 %
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5%
No. with + reactions:
11
Total no. in group:
18
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
5%
No. with + reactions:
5
Total no. in group:
18
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
5%
No. with + reactions:
8
Total no. in group:
18
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5%
No. with + reactions:
5
Total no. in group:
118

Any other information on results incl. tables

Maximization Test: Test group results after challenge:

 Form of application: right flank: 2% in aqua bidest.                               
Animal No.  1  2  3  4  5  6  7  8  10
Findings 24 h after removal of the patch  0/0  0/0  0/0  0/0  0/0  0/0  0/0  0/0  0/0  0/0
Findings 48 h after removal of the patch  0/0  0/0  0/0  0/0  0/0  0/0  0/0 0/0   0/0 0/0

x/y: Erythema/Edema

The intradermal induction with 0.5% test substance preparations caused slight to well-defined signs of skin irritation in all test group animals. After the percutaneous induction with a 10% test substance preperation incrustation, partially open (caused by the intradermal induction) could be observed in addition to well-defined erythema and slight edema in all test group animals.

After the challenge with a 2% test substance preparation the animals of control group1 (no application on animals of control group 2) and the test group animals did not show any skin reactions 24 and 48 hours after removal of the patches.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The intradermal induction with dimethyl piperazine with 0.5% test substance preparations caused slight to well-defined signs of skin irritation in all test group animals. After the percutaneous induction with a 10% test substance preperation incrustation, partially open (caused by the intradermal induction) could be observed in addition to well-defined erythema and slight edema in all test group animals. After the challenge with a 2% test substance preparation the animals of control group 1 (no application on animals of control group 2) and the test group animals did not show any skin reactions 24 and 48 hours after removal of the patches. Based on these results and according to the criteria laid down in the CLP Regulation, the substance is considered not classified as skin sensitizer.