1,2,3-Oxadiazolium, 5-amino-3-(4-morpholinyl)-, chloride (1:1)

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A guinea pig maximisation test was already available before the actual requirement for a LLNA-test was released.

Test material

Test material information

Constituent 1

Reference substance name:

5-amino-3-(morpholin-4-yl)-1,2,3-oxadiazolidin-3-ium chloride

EC Number:

605-254-1

Cas Number:

16142-27-1

Molecular formula:

C6 H11 N4 O2 . Cl

IUPAC Name:

5-amino-3-(morpholin-4-yl)-1,2,3-oxadiazolidin-3-ium chloride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Linsidomin Substanz
- Physical state: white powder
- Lot/batch No.: W003
- Storage condition of test material: brown glass bottle, room temperature, dark

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Twenty-three female, albino Dunkin-Hartley guinea pigs were supplied by David Hall Limited, Burton-on-Trent, Staffordshire, U.K. At the start of the main study the animals weighed 344-445 g, and were approximately eight to twelve weeks old. After a minimum acclimatisation period of five days, each animal was selected at random and given a number unique within the study which was written on a small area of clipped rump using a black indelible marker-pen.

The animals were housed in groups of up to two in solid-floor polypropylene cages furnished with wood flakes. Free access to mains tap water and food (Guinea Pig FD1 Diet, Special Diets Services Limited, Witham, Essex, U.K.) was allowed throughout the study.

The animal room was maintained at a temperature of 20-23°C and relative humidity of 34–59 %. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

arachis oil

Induction 2

Concentration / amount:

Topical induction: 50 % w/w
Topical Challenge: 50 % and 25 % w/w

Challenge

Challenge 1

Route:

intradermal

Vehicle:

arachis oil

Challenge 2

Concentration / amount:

Topical induction: 50 % w/w
Topical Challenge: 50 % and 25 % w/w

No. of animals per dose:

5 per group.

Details on study design:

The method used for assessing the sensitising properties of the test material was based on the Guinea Pig Maximisation test of Magnusson B. & Kligman A.M., J. Invest. Dermatol. (1969) 52: 268 - 276.

Challenge controls:

5 Animals were used as negative controll group.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

9

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Results 2

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

9

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

Main Study

a) Skin Reactions Observed After Intradermal Induction

Well-defined erythema was noted at the intradermal induction site of one test group animal at the 24-hour observation. Very slight erythema was noted at the intradermal induction sites of all other test group animals at this time. Very slight erythema was noted in five test group animals at the 48-hour observation.

No erythema was noted at the intradermal induction sites of control group animals at the 24 and 48-hour observations.

b) Skin Reactions Observed After Topical Induction

Very slight to well-defined erythema with very slight to slight oedema was noted at the induction sites of all test group animals at the one-hour observation. Bleeding of the treatment site was commonly noted. Residual test material was also noted at four induction sites.

Very slight to well-defined erythema persisted at the induction sites of nine test group animals at the 24-hour observation. Very slight oedema was noted at four treatment sites. Small superficial scattered scabs were noted at eight induction sites at this time.

No skin reactions were noted at the treatment sites of control group animals at the 1 and 24-hour observations.

c)Skin Reactions Observed After Topical Challenge

 

50% w/w in Arachis Oil B.P.

Positive sensitisation reactions (erythema grades 1 or 2 with without oedema) were noted at the challenge sites of nine test group animals at the 24-hour observation. These reactions persisted at the challenge sites of six test group animals at the 48-hour observation. Other adverse skin reactions (crust formation with loss of skin elasticity) prevented accurate evaluation of erythema and oedema at the challenge sites of a further two test group animals at this time. Desquamation was commonly noted.

No skin reactions were noted at the challenge sites of control group animals at the 24 and 48-hour observations.

25% w/w in Arachis Oil B.P.

Positive sensitisation reactions (erythema grades 1 or 2 with without oedema) were noted at the challenge sites of nine test group animals at the 24-hour observation. These reactions persisted at the challenge sites of six test group animals at the 48-hour observation. Other adverse skin reactions (crust formation with loss of skin elasticity) prevented accurate evaluation of erythema and oedema at the challenge sites of a further two test group animals at this time. Desquamation was commonly noted.

No skin reactions were noted at the challenge sites of control group animals at the 24 and 48-hour observations.

Bodyweight

Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material, LINSIDOMIN SUBSTANZ, produced a 90% (9/10) sensitisation rate and was classified as an EXTREME SENSITISER to guinea pig skin.
The test material was also classified as a sensitizer according to EC labelling regulations. The risk phrase R 43 "MAY CAUSE SENSITISATION BY SKIN CONTACT" is therefore required. According to EG 1272/2008 the substance was classified as skin sensitizer class 1A. The risk phrase H317 "May cause an allergic skin reaction" is required.