3-methyl-1-vinyl-1H-imidazolium methyl sulphate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and 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

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study was already available and conducted before LLNA was chosen as prefered test system.

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-1-vinyl-1H-imidazolium methyl sulphate

EC Number:

247-832-2

EC Name:

3-methyl-1-vinyl-1H-imidazolium methyl sulphate

Cas Number:

26591-72-0

Molecular formula:

C6H9N2.CH3O4S

IUPAC Name:

1-ethenyl-3-methyl-1H-imidazol-3-ium methyl sulfate

Details on test material:

Name of the test substance used in the study report: 3-Methyl-l-vinylimidazolium methosulfat
Degree of purity / content: 46.4 g/100 g in water, regarded as 100 % substance preparation

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH
- Age at study initiation: young adult animals
- Weight at study initiation: 326 - 378 g
- Housing: 5 animals/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

epicutaneous induction: not further diluted => 46.4 %
intradermal induction: 5 % => 2.32 %
epicutaneous challenge: 75% => 34.8 %

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

epicutaneous induction: not further diluted => 46.4 %
intradermal induction: 5 % => 2.32 %
epicutaneous challenge: 75% => 34.8 %

No. of animals per dose:

10 (test group)
5 (control group 1) + 5 (control group 2)

Details on study design:

RANGE FINDING TESTS:
The concentrations of the test substance suitable for use in the main experiment were determined in a pretest.
Two 24-hour percutaneous occlusive applications were performed within 96 hours. The minimum irritant
concentration was found to be the undiluted test substance (=> 46.4 % in water). The maximum non-irritant concentration was
found to be a 75 % test substance preparation in aqua bidest (=> 34.8 % in water).
Applicability: it was possible to inject a 5 % test substance preparation in 0 .9 % aqueous NaCl-solution resp . in Freund's adjuvant / 0 .9 % aqueous NaClsolution (1 : 1) with a syringe (=> 2.32 %).

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal induction :
- 6 intradermal injections in groups of two per animal
Injections for the test group:
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 NaCl-solution (1 : 1) with test substance
Injections for control groups 1 and 2:
- The animals were given the same injections (A, B,C) but without test substance, only with the formulating agent.
Site of application :
- shoulder
Readings :
- 24 h after the beginning of application
Assessment of the skin findings :
- analogous to the pretest
Percutaneous induction :
- Percutaneous induction was carried out one week after intradermal induction.
Amount applied :
2 x 4 cm filter paper strips containing the test substance were applied to the skin of the shoulder under an occlusive dressing . The filter paper strip was soaked in the test substance. The dressing consisted of rubberized linen patches (4 x 6 cm from Russka) and Fixomull Stretch (adhesive fleece) from Beiersdorf AG.
The control groups were not treated, since the test substance was applied undiluted and thus no solvent was used.
Duration of exposure :
- 48 hours
Site of application :
- shoulder, same area as in the case of the previous intradermal application
Readings:
- 48 h after the beginning of application
Assessment of skin findings:
- analogous to the pretest

B. CHALLENGE EXPOSURE
The challenge was performed 14 days after the percutaneous induction.
Amount applied :
2 x 2 cm filter paper strips containing the test substance formulation were applied to the skin of the
flank under an occlusive dressing. The filter paper strip was soaked in the test substance formulation.
The dressing consisted of rubberized linen patches
(4 x 4 cm from Russka), patches of Idealbinde (5 x 5 cm from Pfälzische Verbandstoff-Fabrik) and Fixomull Stretch (adhesive fleece) from Beiersdorf
A.G .
- The test group and control group 1 were treated with the test substance formulation (control group 2 remained untreated) .
Duration of exposure :
- 24 hours
Site of application :
- intact flank
Readings :
- 24 and 48 h after the removal of the patch
Assessment of skin findings :
- analogous to the pretest

Positive control substance(s):

yes

Remarks:

Alpha-Hexylcinnamaldehyde techn . 85%

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

75% => 34.8 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75% => 34.8 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

other: control group 1

Dose level:

control

No. with + reactions:

0

Total no. in group:

4

Clinical observations:

one animal died due to pneumonia

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control group 1. Dose level: control. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal died due to pneumonia.

Any other information on results incl. tables

Induction

After the intradermal induction well-defined erythema and slight edema were observed at the injection sites

of all control group animals and all test group animals, at which only Freund's adjuvant / 0 .9% aqueous

NaCl-solution (1 : 1) was applied . Injections of 5% test substance preparations in 0 .9% aqueous NaClsolution

or in Freund's adjuvant / 0 .9% aqueous NaClsolution (1 : 1) caused well-defined erythema and slight edema in all test group animals. The injection sites of all control group animals, at which 0 .9% aqueous NaCl-solution was applied, did not show any

skin reactions.

After the percutaneous induction with the undiluted test substance (=> 46.4 %) 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.

Challenge

The challenge with a 75% (=> 34.8 %) test substance preparation did not cause any skin reactions, neither in control

group 1 nor in the test group 24 and 48 hours after removal of the patches.

Since no borderline results were observed, a 2nd challenge was not performed.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information