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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:
key study
Study period:
19 January 1998 - 21 March 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Performed according to OECD test guidelines and GLP principles.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): XDI (MR-6A)
- Physical state: Colourless liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 338 to 426 g
- Housing: animals were housed singly or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum (Guinea Pig FD1 Diet, Special diets services limietd, Witham, Essex, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimatisation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 37-58
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Remarks:
BP
Concentration / amount:
Sighting tests:
For Intradermal induction concentrations 0.01%, 0.05%, 0.1%, 0.5%, 1% and 5% w/v
For Topical induction concentration 25%, 50%, 75%, 100% v/v
For Topical challenge concentration 25%, 50%, 75% and 100% v/v
Main test:
Intradermal induction: 0.01% w/v in arachis oil BP, 0.01% w/v in a mixture of Freund's complete adjuvant plus distilled water (1:1)
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied and 75% v/v in arachis oil BP
Topical rechallenge: 50% and 25% v/v in arachis oil BP
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Remarks:
BP
Concentration / amount:
Sighting tests:
For Intradermal induction concentrations 0.01%, 0.05%, 0.1%, 0.5%, 1% and 5% w/v
For Topical induction concentration 25%, 50%, 75%, 100% v/v
For Topical challenge concentration 25%, 50%, 75% and 100% v/v
Main test:
Intradermal induction: 0.01% w/v in arachis oil BP, 0.01% w/v in a mixture of Freund's complete adjuvant plus distilled water (1:1)
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied and 75% v/v in arachis oil BP
Topical rechallenge: 50% and 25% v/v in arachis oil BP
No. of animals per dose:
Main test: 10 test and five control animals were used
Details on study design:
RANGE FINDING TESTS: Selection of concentrations for main study
Intradermal induction: 0.01%, 0.05%, 0.1%, 0.5%, 1% and 5% were injected. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically was selected for intradermal induction.
Topical induction: 25%, 50%, 75% and 100% was applied, highest concentration producing only mild to moderate dermal irritation was selected.
Topical challenge: 100%, 75%, 50% and 25% were applied occlusively for a period of 24 hours. The highest non irritant concentration and one lower concentration were selected for the topical challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three injections, 0.1 ml each: Freund's Complete Adjuvant plus distilled water in ratio 1:1, a 0.01% w/v formulation of the test material in arachis oil BP, a 0.01% w/v formulation of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.
- Exposure period: 24 and 48 hours after intradermal injection degree of erythema was evaluated. One week later Day 7, same region was clipped again and treated with a topical application of the undiluted test material. An occlusive dressing, including a filter paper saturated with undiluted test material, was kept in place for 48 hours. Degree of erythema was quantified 1 and 24 hours following removal of the patches.
- Control group: Identical procedure as test animals, 2nd and 3rd intradermal injections consisted of arachis oil BP, subsequently a 50% w/v formulation of arachis oil BP in Freund's Complete Adjuvant/distilled water 1:1. Topical applications also same procedure except nothing was applied to filter paper.
- Site: 40x60 mm area, hair was removed on the shoulder region
- Duration: 21 days

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge: Day 21
- Exposure period: A filter paper saturated with the undiluted test material on the right flank a filter paper saturated with 75% v/v test material was applied to the left skin site. Patches were occluded. After 24 hours, dressing removed, challenge sites swabbed.
- Control group: All animals were treated the same.
- Site: An area of 50x70 mm on both flanks of each animal was clipped free of hair with veterinary clippers.
- Evaluation (hr after challenge): 24 + 48 after dressing removal

C. RECHALLENGE
- 20 days after original challenge, animals (test and control) were re-challenged on previously untreated areas of skin using 50% and 25% test material.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole

Results and discussion

Positive control results:
A summary of positive control data fro the Magnusson and Kligman Maximisation study was included. Last result is from November 1997 restulting in 90% incidence of sensitisation.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
50 and 25%
No. with + reactions:
8
Total no. in group:
8
Clinical observations:
Same results 48 hours after challenge. One animal found dead on Day 8 and one animal killed for humane reasons on Day 10.
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50 and 25%. No with. + reactions: 8.0. Total no. in groups: 8.0. Clinical observations: Same results 48 hours after challenge. One animal found dead on Day 8 and one animal killed for humane reasons on Day 10. .
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
50 and 25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Same results 48 hours after challenge. Two animals showed physical damage caused during dressing removal.
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 and 25%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: Same results 48 hours after challenge. Two animals showed physical damage caused during dressing removal..

Any other information on results incl. tables

After challenge, both in test as well as the control group, very slight to well defined erythema were noted at the challenge sites sometimes together with very sligh oedema.

At 50%: After re-challenge very slight erythema was noted in one animal of the control group. Positive oedema responses were noted at challenge sites of all test group animals at the 24-h observation and five test group animals at the 48-h observation (erythema could not be scored due to adverse reactions). At 25%: no skin reactions were noted in the control group. Positive skin responses were noted at the challenge site of all animals at 24 hr observation and in 7/8 animals at 48 hr observation.

Bodyweight gains in test group were comparable to control group animals.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
XDI produced a 100% (8/8) sensitisation rate and was classified as an extreme sensitiser to guinea pig skin. According to EU labelling regulations: Xi and R43.