Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 15, 1992 - October 21, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles. Limited information available to verify the composition of the used test substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(1984)
Deviations:
no
Principles of method if other than guideline:
"Experimental Skin Sensitization in the Guinea pig and Man", Buehler E.V. and Griffith F. in: Animal models in dermatology (ed. H.I. Maibach), pp. 56-66, Edinburgh, Churchill Livingstone, 1975.
GLP compliance:
yes
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): KY-MA
- Physical state: Light yellow solid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Himalayan
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: Approx. 9 weeks
- Weight at study initiation: 357 - 517 grams
- Housing: Group housing of 2 animals in labelled metal cages with wire-mesh floors.
- Diet (e.g. ad libitum): Free access to standard guinea pig diet, including ascorbic acid (LC 23-B, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands). In addition, hay (B.M.I., Helmond, The Netherlands) was provided once a week.
- Water (e.g. ad libitum): Free access to tap-water, diluted with decalcified water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Preliminary study: 50%, 25%, 10% and 5%
Main study: 25%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Preliminary study: 50%, 25%, 10% and 5%
Main study: 25%
No. of animals per dose:
Preliminary study: 5
Main study: Experimental group: 20; control group: 10
Details on study design:
RANGE FINDING TESTS: One animal was treated epicutaneously at the shaved left flank with 0.5 mL of a 50% concentration of the test substance using a Scotchpak-non-woven patch (2.5 x 2.2 cm) mounted on Micropore tape and held in place with Coban elastic bandage. After 24 hours, the dressings and residual test substance were removed using a tissue moistened with tap-water. The treated skin was assessed for erythema and oedema, 24 and 48 hours after bandage removal.
Four further animals were shaved on the left flank and exposed to 0.05 mL of 50%, 25%, 10% and 5% (w/w) concentrations of the test substance, occlusively administered by means of Square chambers mounted on Micropore tape. The bandage was fixed in place by means of Coban elastic bandage. After 6 hours, the dressings and residual test substance were removed using a tissue moistened with tap-water. The reaction sites were assessed for erythema and oedema, 24 and 48 hours after bandage removal.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: nine during a period of 3 weeks (days 1, 3, 5, 8, 10, 12, 15, 17 and 19).
- Exposure period: 6 hours. The treated skin area was scored immediately after removal of the dressings on day 19.
- Test groups: one
- Control group: one
- Site: left flank
- Concentrations: 25%

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: ten days after the last induction (day 29)
- Exposure period: 6 hours
- Test groups: one
- Control group: one
- Site: right flank
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48 hours after removal of the dressings
Positive control substance(s):
yes
Remarks:
periodically with Formaldehyde.

Study design: in vivo (LLNA)

Statistics:
Not performed.

Results and discussion

Positive control results:
See the document Summary of positive control data Buehler test in the attached background material.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No symptoms of systemic toxicity were observed in the animals of the main study during the study period. No mortality occurred during this main study.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No symptoms of systemic toxicity were observed in the animals of the main study during the study period. No mortality occurred during this main study..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No symptoms of systemic toxicity were observed in the animals of the main study during the study period. No mortality occurred during this main study.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No symptoms of systemic toxicity were observed in the animals of the main study during the study period. No mortality occurred during this main study..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No symptoms of systemic toxicity were observed in the animals of the main study during the study period. No mortality occurred during this main study.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No symptoms of systemic toxicity were observed in the animals of the main study during the study period. No mortality occurred during this main study..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No symptoms of systemic toxicity were observed in the animals of the main study during the study period. No mortality occurred during this main study.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No symptoms of systemic toxicity were observed in the animals of the main study during the study period. No mortality occurred during this main study..

Any other information on results incl. tables

Preliminary study:

No skin irritation and no signs of systemic toxicity were observed in the animals of the preliminary study during the study period. However, body weight loss was noted in one of the five animals.

The choice of propylene glycol as vehicle in this test was based on the fact that propylene glycol produced the best usable suspension. However, the 25% test substance concentration was chosen as the highest usable concentration in the main study, as higher concentrations were too viscous and dry.

Main study:

- Induction: Three experimental animals showed slight erythema after the last epicutaneous induction exposure. No skin irritation was observed in the other experimental animals.

- Body weights: The average body weight gain of experimental and control animals was similar.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a Buehler test performed according to OECD Guideline 406 (1981) and GLP principles, KY-MA showed no skin sensitising properties.
Executive summary:

Nine epicutaneous exposures of KY-MA in the induction phase resulted in slight erythema in three animals and no skin irritation in the other experimental animals. The epicutaneous exposure of KY-MA in the challenge phase resulted in no sensitisation reactions in response to the 25% test substance concentration. Therefore, the substance needs not to be classified as a skin sensitiser in accordance with the CLP Regulation.