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Skin sensitisation

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Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 March 1998 to 14 May 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to GLP and internationally accepted test guidelines.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Qualifier:
equivalent or similar to
Guideline:
other: Guinea Pig Maximisation test of Magnusson B & Kligman A M, J. Invest. Dermatol. (1969) 52:268-276
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A Guinea Pig Maximisation study result which pre-dates the OECD guideline for the LLNA is available and the study is considered to be of sufficient reliability to satisfy the data requirement. On this basis it is considered that a supplementary LLNA would not be appropriate.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately eight to twelve weeks old
- Weight at study initiation: animals weighed 328 to 405g
- Housing:animals were housed singly or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Free access to mains tap water was allowed throughout the study.
- Water (e.g. ad libitum):Free access to food (Guinea Pig FD1 Diet, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Acclimation period:at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 21
- Humidity (%): 46 to 60%.
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light):twelve hours continuous light and twelve hours darkness


IN-LIFE DATES: From: 16 March 1998 To: 14 May 1998
Route:
intradermal and epicutaneous
Vehicle:
other: Freund's Complete Adjuvant
Concentration / amount:
0.05% water/vehicle emulsion
Route:
epicutaneous, occlusive
Vehicle:
other: Freund's Complete Adjuvant
Concentration / amount:
0.05% water/vehicle emulsion
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
Intradermal Induction-Range Finding
4 guinea pigs, each received four 0.1 ml injections of either 5%, 1%, 0.5% or 0.1% w/v in distilled water. Observed and assess 24, 48, and 72 hours and 7 days after injection. The highest concentration causing only mild to moderate skin irritation, and which was well tolerated systemically, was selected for the the intradermal induction stage of main study.

Topical Induction-Range Finding
Two guinea pigs were treated with undiluted test material and three preparations of the test material (75%, 50%, and 25% v/v in distilled water). An additional two guinea pigs were treated with four preparations of the test material (25, 10, 5 and 2% v/v in distilled water). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 48 hours. The degree of erythema and oedema was evaluated 1, 24 and 48 hours after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.

Topical Challenge-Range Finding
Four preparations of the test material (10, 5, 2, and 1% v/v in distilled water) wer applied to the clipped flanks of two guinea pigs under occlusive dressings for an exposure period of 24 hours. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to 15 days. The degree of erythema and oedema was evaluated approximately 1, 24, and 48 hours after dressing removal. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.

MAIN STUDY
10 test and five control animals were used in the test

A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period:Intradermal application made on day 0; topical application made 7 days after the intradermal induction.
- Test group: 10 animals
- Control group: 5 animals
- Site: 40 mm x 60mm
- Frequency of applications: twice, seven days apart. first intradermal, second topical
- Duration: 48 hours (Topical appication), performed 7 days after the intradermal application.
- Concentrations: (0.1ml)
Test
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) a 0.05% w/v emulsion of the test material in distilled water
c) a 0.05% w/v emulsion of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.
Control
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) distilled water
c) a 50% w/v formulation of distilled water in Freund's Complete Adjuvant/distilled water 1:1

B. CHALLENGE EXPOSURE
- No. of exposures: 2 (each on opposite flanks)
- Day(s) of challenge: begin day 21
- Exposure period: 48 hours
- Test groups: 10 animals
- Control group: 5 animals
- Site: 20 mm x 20 mm
- Concentrations: 1 % and 2% v/v in distilled water
- Evaluation (hr after challenge): 24 and 48


Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2 % v/v in distilled water
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: 2 % v/v in distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
other: not reported
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Remarks on result:
other: not reported
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
2% v/v in distilled water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2% v/v in distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
other: not reported
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Remarks on result:
other: not reported
Interpretation of results:
GHS criteria not met
Conclusions:
The test material produced a 0% (0 reactions / 10 animals) sensitisation rate and was classified as a non-sensitiser to guinea pig skin. The test material did not meet the criteria for classification as a sensitiser according to EU labelling regulatoins. No risk phrase is required.
Executive summary:

A study was performed to assess the contact sensitisation potential of the test material in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

Intradermal Induction:       0.05% w/v in distilled water

Topical Induction:              5% v/v in distilled water

Topical Challenge:              2% and 1% v/v in distilled water

The test material produced a 0% (0 reactions / 10 animals) sensitisation rate and was classified as a non-sensitiser to guinea pig skin. The test material did not meet the criteria for classification as a sensitiser according to EU labelling regulations.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the available information indicates that the substance should be classified for respiratory sensitisation or corrosivity
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A study was performed to assess the contact sensitisation potential of the test material in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Ten test and five control animals were used for the main study.

Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

Intradermal Induction:       0.05% w/v in distilled water

Topical Induction:              5% v/v in distilled water

Topical Challenge:              2% and 1% v/v in distilled water

The test material produced a 0% (0 reactions / 10 animals)

sensitisation rate and was classified as a non-sensitiser to guinea pig skin. The test material did not meet the criteria for classification as a sensitiser according to EU labelling regultions.

Migrated from Short description of key information:
Sensitization test in Guinea Pigs (Magnusson-Kligman test) - not sensitising (0/10 reactions found).

Justification for classification or non-classification

No evidence of sensitisation (delayed-contact hypersensitivity) was found for 1,3 -BAC in an adjuvant-type test (Magnusson-Kilgmann test). On the evidence of this study, there is no basis on which to classify the test substance as a dermal sensitiser.