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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 November 1982 - 5 December 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliability 2 is assigned because the study conducted similar to OECD TG 406 (GPMT), without GLP and with minor deviations that do not influence the quality of the results.
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Test material information:
Composition 1
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire
- Age at acclimatization start: 4-6 weeks
- Weight at acclimatization start: 310-417 g
- Housing: suspended cages with wire mesh floors
- Diet: free access to Vitamin C-enriched guinea pig diet (Special Diets Services Limited)
- Water: free access to tap water
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS (check details)
- Temperature (°C): +/- 21
- Humidity (%): 30-70
- Air changes (per hr): +/- 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
- 5% (v/v) for the intradermal induction
- Undiluted (100%) for the epidermal induction
- 1%, 5%, 10% and 20% (v/v) for the challenge
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
- 5% (v/v) for the intradermal induction
- Undiluted (100%) for the epidermal induction
- 1%, 5%, 10% and 20% (v/v) for the challenge
No. of animals per dose:
Test animals: 15
Control animals: 15
Details on study design:
RANGE FINDING TESTS
Intradermal and topical irritancy of a range of dilutions of the test substance in liquid paraffin was investigated to identify irritant test substance concentrations suitable for the induction phase of the main study. A range of non-irritant concentrations was selected for the challenge phase following consultation with the Sponsor.

MAIN STUDY
A. INDUCTION EXPOSURE
1) Intradermal injections
- Concentration: 5%
- Site: the dorsal scapular region (clipped free of hair)

Test group (three pairs of 0.1 mL intradermal injections):
1) Freund's complete adjuvant (FCA) 50:50 with water
2) Test substance at 5% (v/v) in vehicle
3) Test substance at 5% (v/v) in a 50:50 mixture of FCA with vehicle

Control group (three pairs of 0.1 mL intradermal injections):
1) Freund's complete adjuvant (FCA) 50:50 with water
2) Vehicle
3) 50:50 mixture of FCA with vehicle

2) Topical applications one week after the injections:
- Site: the dorsal scapular region (clipped and shaved free of hair)
- Concentration: test animals undiluted test article (100%), control animals no data (page missing in report)
- Amount: saturated patch
- Area: 8 cm2
- Exposure period: 48 hours (occlusive)

B. CHALLENGE EXPOSURE (control and test group)
- Concentrations: 1%, 5%, 10% and 20%
- Evaluation: 24, 48 and 72 hours after start of challenge
- Other information on challenge exposure: no data (page missing in report)
Positive control substance(s):
no
Reading:
other: 24, 48 and 72 hours after challenge
Group:
negative control
Dose level:
1%
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading:
Reading:
other: 24, 48 and 72 hours after challenge
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading:
Reading:
other: 24, 48 and 72 hours after challenge
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading:
Reading:
other: 24, 48 and 72 hours after challenge
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading:
Reading:
other: 24, 48 and 72 hours after challenge
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading:
Reading:
other: 24, 48 and 72 hours after challenge
Group:
test group
Dose level:
5%
No. with + reactions:
8
Total no. in group:
15
Remarks on result:
other: Reading:
Reading:
other: 24, 48 and 72 hours after challenge
Group:
test group
Dose level:
10%
No. with + reactions:
7
Total no. in group:
15
Clinical observations:
Result in one animal was inconclusive
Remarks on result:
other: Reading:
Reading:
other: 24, 48 and 72 hours after challenge
Group:
test group
Dose level:
20%
No. with + reactions:
12
Total no. in group:
14
Clinical observations:
Result in one animal was inconclusive, one animal was excluded
Remarks on result:
other: Reading:

Results of the three readings (24, 48 and 72 hours after start of challenge) are summarized per challenge concentration. From one guinea-pig the patch was lost during the 4th challenge (20% test substance) application. No scores were therefore recorded for this animal on this occasion.

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, performed in accordance with a method similar to OECD 406, it was observed that skin sensitisation occurred in >30% of the test animals at tested concentrations at and above 5%, but not at 1%. Based on these results, the test substance can be considered a skin sensitiser.
Executive summary:

The skin sensitisation potential of the substance was investigated by performing a guinea pig maximisation test performed in accordance with a method similar to OECD 406 (GPMT), but there is no indication of GLP compliance. A concentration of 5% was used for the intradermal induction, 100% (undiluted test article) for the epidermal induction and 1%, 5%, 10% and 20% for the challenge. In the 1% test group none of the fifteen animals showed a sensitisation response. In the groups exposed to 5%, 10% and 20% of the test sample, 8/15 animals (53%), 7/15 animals (47%) and 8/14 animals (86%) showed a positive response, respectively. Based on these results the substance is considered to be a skin sensitiser as >30% of the animals showed sensitisation at these concentrations.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:
Migrated from Short description of key information:
The skin sensitisation potential of the substance was investigated by performing a guinea pig maximisation test performed in accordance with a method similar to OECD 406, but there is no indication of GLP compliance. A concentration of 5% was used for the intradermal induction, 100% (undiluted test article) for the epidermal induction and 1%, 5%, 10% and 20% for the challenge. In the 1% test group none of the fifteen animals showed a sensitisation response. In the groups exposed to 5%, 10% and 20% of the test sample, 8/15 animals (53%), 7/15 animals (47%) and 8/14 animals (86%) showed a positive response, respectively. Based on these results the substance is considered to be a skin sensitiser as >30% of the animals showed sensitisation at these concentrations.

Justification for selection of skin sensitisation endpoint:
The result of this study is sufficiently reliable and sufficiently adequate for covering this endpoint.

Justification for classification or non-classification

According to the criteria outlined in Annex VI of 67/548/EEC (DSD) and Annex I of 1272/2008/EC (CLP), the substance needs to be classified as a skin sensitizer (Skin Sens. 1B, H317) as at an intradermal induction concentration of 5% (the highest concentration tested) more than 30% response were seen at the challenge phase.