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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Published: 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Development and Validation of an Alternative Dermal Sensitization Test: The Mouse Ear Swelling Test (MEST)
Author:
S. C. Gad, B. J. Dunn, D. W. Dobbs, C. Reilly, and R. D. Walsh
Year:
1986
Bibliographic source:
Toxicology and Applied Pharmacology 84, 93-114 (1986)

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Swelling of mouse ear measured after induction and challenge with test substance (MEST).
GLP compliance:
not specified
Type of study:
mouse ear swelling test

Test material

Constituent 1
Chemical structure
Reference substance name:
Perhydroazepine
EC Number:
203-875-9
EC Name:
Perhydroazepine
Cas Number:
111-49-9
Molecular formula:
C6H13N
IUPAC Name:
azepane
Details on test material:
- Name of test material (as cited in study report): Hexamethylenimine
- purity: >= 98 %

In vivo test system

Test animals

Species:
mouse
Strain:
CF-1
Sex:
female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: epicutanous, open (TEST 1) or occlusive (TEST 2)
Vehicle:
other: epicutanous open (TEST 1): acetone ; epicutanous occlusive (TEST 2): propylene glycol
Concentration / amount:
epicutanous open (TEST 1): 1 %
epicutanous occlusive (TEST 2): 1 %
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: epicutanous open (TEST 1): acetone ; epicutanous occlusive (TEST 2): propylene glycol
Concentration / amount:
epicutanous open (TEST 1): 1 %
epicutanous occlusive (TEST 2): 1 %
No. of animals per dose:
epicutanous open (TEST 1): 10-15 animals, 6-10 weeks old
epicutanous occlusive (TEST 2): no number indicated, 6-10 weeks old
Details on study design:
RANGE FINDING TESTS: yes, systemic toxicity is basis for selection of concentration.

MAIN STUDY
(TEST 1)
A. INDUCTION EXPOSURE, epicutanous, open
- No. of exposures: 4
- Exposure period: 4 days
- Control group: vehicle only
- Site: abdominal skin
- Frequency of applications: daily
- Duration: no removal of test substance
- Concentrations: 1 %
- Remark: on day 0 prior to substance exposure intradermal injection of Freund's Complete Adjuvant

(TEST 2)
A. INDUCTION EXPOSURE, epicutanous, occlusive
- No. of exposures: 3
- Exposure period: 6 days
- Control group: vehicle only
- Site: abdominal skin
- Frequency of applications: on days 0, 2 and 4
- Duration: each patch stayed on the skin for 24 h
- Concentrations: 1 %
- Remark: on day 0 prior to substance exposure intradermal injection of Freund's Complete Adjuvant

(TEST 1 and 2)
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1, challenge at 10 days (epicutanous, open, i.e. TEST 1) or 11 days (epicutanous, occlusive, i.e. TEST 2) after induction.
- Site: ear
- Concentrations: 5 %
- Evaluation (hr after challenge): 24 and 48 h after exposure

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: TEST 1, i.e. epicutanous, open: not clarified if the results are from the 24 or 48 h reading
Group:
test chemical
Dose level:
1 %
Clinical observations:
40 % responese, 106 % swelling
Remarks on result:
other: Reading: other: TEST 1, i.e. epicutanous, open: not clarified if the results are from the 24 or 48 h reading. Group: test group. Dose level: 1 %. Clinical observations: 40 % responese, 106 % swelling.
Reading:
other: TEST 2, i.e. epicutanous occlusive: not clarified if the results are from the 24 or 48 h reading
Group:
test chemical
Dose level:
1 %
No. with + reactions:
0
Clinical observations:
0 % response, 101 % swelling
Remarks on result:
other: Reading: other: TEST 2, i.e. epicutanous occlusive: not clarified if the results are from the 24 or 48 h reading. Group: test group. Dose level: 1 %. No with. + reactions: 0.0. Clinical observations: 0 % response, 101 % swelling.

Applicant's summary and conclusion

Conclusions:
Under open epicutanous conditions the test item has sensitizing effects in a MEST. Using the a non standard protocol (repeated patch protocol, epicutaneous occlusive) none of the animals showed a positive test result. Therefore the results are considered ambiguous.
Executive summary:

Sensitising properties of the test substance were investigated using a mouse ear swelling test (MEST). Therefore 10 -15 female CF-1 mice were treated under either epicutanous, open (standard) or occlusive (patch test) conditions. The test substance was applied as a 1% solution.

Using the standard protocol (epicutaneous open) the test substance showed sensitizing effects (40% sensitised; positive when left ear was at least 20% thicker than the right ear). Using the repeated patch protocol none of the animals showed a positive test result.

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