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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-04-27 to 1988-06-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: - guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The described guinea pig sensitisation test (Buehler test) according to OECD 406 was conducted in 1988 before the guidance for the LLNA (OECD429, first adopted in 2002) was available, and before the method was fully established and validated. And since the result of the Buehler test is considered to be scientifically valid, the test was not repeated also taking into account exposure and animal welfare considerations.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Albino Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in-house breeding facility
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: 270 - 410 g
- Housing: 1 per cage (stainless steel cages with grating floor)
- Diet: ad libitum
- Water: ad libitum, twice weekly ascorbic acid was added)
- Acclimation period: 1 day


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 +- 1
- Humidity (%): 55 +- 10
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: polyethylene glycol 400 (PEG 400), Windsor Laboratories Limited
Concentration / amount:
- 0.01 % (maximum non-irritating concentration after intradermal injection, as determined during a preliminary study). The same concentration was used also for challenge exposure.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: polyethylene glycol 400 (PEG 400), Windsor Laboratories Limited
Concentration / amount:
- 0.01 % (maximum non-irritating concentration after intradermal injection, as determined during a preliminary study). The same concentration was used also for challenge exposure.
No. of animals per dose:
- 12 animals in the treatment group
- 8 animals in the control group
Details on study design:
RANGE FINDING TESTS: no data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Site: scapular region
- Test groups: 12 animals
- Immunostimulation: Freunds Complete Adjuvant (FCA)
- Control group: 8 animals, treated only with vehicle
- Day 1: first induction, intradermal application
- clipping of an area of 4 cm x 6 cm of the scapular region
- three pairs of intradermal injections (0.1 mL) in the neck of the animals:
mixture of adjuvant and PEG 400 (1:1) (treatment group and control group)
test compound 0.01 % in PEG 400 (treatment group) OR PEG 400 alone (control group)
test compound 0.01 % in a mixture of FCA:PEG 400 (1:1) (treatment group) OR FCA:PEG 400 (1:1) alone (control group)

- Day 7:
- clipping of an area of 4 cm x 6 cm of the scapular region

- Day 8: second induction, epicutaneous application
- test compound 0.01 % in PEG 400 (treatment group) OR PEG 400 alone (control group)
- exposure to the clipped skin area of the injection sites and coverage with an occlusive patch, secured by elastic bandage (Paso, Poland)
- exposure duration: 48 hours

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Site: flank
- Test groups: 12 animals
- Control group: 8 animals, challenged identically as the test group
- Day 21:
- clipping of an area of 5 cm x 5 cm at both flank regions
- Day 22: challenge, epicutaneous application
- application of 0.01 % of the test compound in PEG 400 with an occlusive patch (Polovis, Poland) to the left flank and PEG 400 alone with an occlusive patch to the right flank
- exposure duration: 24 h
- Day 24 and 25: evaluation
- 24 h and 48 h after removal of the dressing the reactions were graded according to the Draize scoring
- Grading according to Draize scoring:
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation
injuries in depth 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond
the area of exposure 4

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.01 %
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.01 %. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: none.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.01 %
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.01 %. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: none.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.01 %
No. with + reactions:
12
Total no. in group:
12
Clinical observations:
slight to severe erythema, slight oedema in two animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.01 %. No with. + reactions: 12.0. Total no. in groups: 12.0. Clinical observations: slight to severe erythema, slight oedema in two animals.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.01 %
No. with + reactions:
12
Total no. in group:
12
Clinical observations:
slight to severe erythma
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.01 %. No with. + reactions: 12.0. Total no. in groups: 12.0. Clinical observations: slight to severe erythma.
Group:
positive control
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
other: Skin sensitizer Category 1A
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this skin sensitization study all animals showed positive reactions at 24h and 48 h (slight to severe erythema at both time points, slight oedema in two animals at the first time point). No deaths occurred during the study period. Based on the results it can be concluded that the test substance is a skin sensitizer.