Registration Dossier

Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Storage condition of test material: under nitrogen in the dark at 4 °C.

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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
Challengeopen allclose all
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

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
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: other: 24, 48 and 72 hours after challenge. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 15.0.
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: other: 24, 48 and 72 hours after challenge. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 15.0.
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: other: 24, 48 and 72 hours after challenge. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 15.0.
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: other: 24, 48 and 72 hours after challenge. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 15.0.
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: other: 24, 48 and 72 hours after challenge. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 15.0.
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: other: 24, 48 and 72 hours after challenge. Group: test group. Dose level: 5%. No with. + reactions: 8.0. Total no. in groups: 15.0.
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: other: 24, 48 and 72 hours after challenge. Group: test group. Dose level: 10%. No with. + reactions: 7.0. Total no. in groups: 15.0. Clinical observations: Result in one animal was inconclusive.
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: other: 24, 48 and 72 hours after challenge. Group: test group. Dose level: 20%. No with. + reactions: 12.0. Total no. in groups: 14.0. Clinical observations: Result in one animal was inconclusive, one animal was excluded.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.