Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
method of Magnusson and Kligman (1970)
Principles of method if other than guideline:
see attached file
GLP compliance:
yes
Type of study:
other: The sensitising properties of the test sample were asse.ssed using the maximisation test of Magnusson and Kligman (1970).

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Substance HI07597
- Sample reference: NBW 8809/52
- Physical state: red powder
- Purity: 100% (w/w)
- Moisture: <0.2%
- CTL reference number: Y04203/002/001

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Barriered Animal Breeding Unit, ICI Pharmaceuticals, Alderley Park, Macclesfield, Gheshire, UK
- Age at study initiation: young adults
- Weight at study initiation: 279-369g
- Weight at positive control study initiation: 262-385g
- Housing: housed individually in suspended cages (37cm length x 32cm width x 20cm height)
- Diet (e.g. ad libitum): free access to food (Labsure RGP Guinea Pig Diet)
- Water (e.g. ad libitum): unl imited access to water vi a an automatic system.
- Acclimation period: minimum of six days prior to the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 2°C
- Humidity (%): 50 ± 10%
- Air changes (per hr): 20-30 air-changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light and 12 hours of darkness.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
See "Details on study design" section.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
See "Details on study design" section.
No. of animals per dose:
A group of thirty female guinea pigs was used for the main study, twenty test and ten control.
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
Before exposure :
A row of three injections (0.05-0.1mL each) was made on each side of the mid-line. The injections were:
(i)Top: Freund's Complete Adjuvant plus 3% DMF in corn oil in the ratio 1:1 ;
(ii) Middle: a 1% (w/v) preparation of the test sample in 3% OMF in corn oil ;
(iii) Bottom: a 1% (w/v) preparation of the test sample ina 1:1 preparation of Freund's Complete Adjuvant plus 3% DMF in corn oil.
The injections were checked for any adverse effects for up to 48 hours.

One week later, the scapular area was clipped again and treated as decribed below :
- No. of exposures: 1
- Exposure period: 48 hours.
- Control group: yes with topical application with corn oil only
- Site: scapular area
- Concentrations: application of 0.25g of 75% (w/v) preparation in corn oil
- Observations: 24 hrs after removal of the dressing.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 24 hrs
- Site: on one or both flanks of all the test and control animals
- Concentrations: A 75% (w/v) preparation of the test sample (approximately 0.13g) was applied to one of the pieces of filter paper and 0.05-0.1ml of a 30% (w/v) preparation in corn oil was applied to the second piece of filter paper. The dressing was placed onto the guinea pig so that the 75% (w/v) preparation was on the right shorn flank and the 30% (w/v) preparation was on the left shorn flank.
- Evaluation (hr after challenge): 24 and 48hrs
Positive control substance(s):
yes
Remarks:
Formaldehyde (40% (w/v) solution in water)

Results and discussion

Any other information on results incl. tables

The substance was assessed for its skin sensitisation potential using the method of Magnusson and Kligman (1970) . Challenge with the test sample caused staining which obscured all application sites. Histopathological examination of the challenge sites revealed that 30% and 75% (w/v) preparations of test substance in corn oil had elicited a skin sensitisation response. In a positive control study, under similar conditions, formaldehyde elicited an extreme sensitisation response in previously-induced guinea pigs .

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: Magnusson B al1ld Kl igman A M (1970)
Conclusions:
Histopathological examination of the challenge sites revealed that 30% and 75% (w/v) preparations of the Substance had elicited a skin
sensitisation response.
Executive summary:

sensitising