Perhydroazepine

Skin sensitisation

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

Test material information

Constituent 1

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)

Induction

Induction 1

Route:

other: epicutanous, open (TEST 1) or occlusive (TEST 2)

Vehicle:

other: epicutanous open (TEST 1): acetone ; epicutanous occlusive (TEST 2): propylene glycol

Induction 2

Concentration / amount:

epicutanous open (TEST 1): 1 %
epicutanous occlusive (TEST 2): 1 %

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

other: epicutanous open (TEST 1): acetone ; epicutanous occlusive (TEST 2): propylene glycol

Challenge 2

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)

Results

Results 1

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.

Results 2

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.