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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline-study performed under QAU Deficiencies: - no details on the composition of the adjuvant mixture - exact guideline was not mentioned ("...study was carried out as recommended in the OECD guidelines 1981....") - diet supplementation with ascorbic acid is equivocal - no details on the pilot/range finder study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1981
Deviations:
yes
Remarks:
no details on the composition of the adjuvant mixture; exact guideline was not mentioned ("..study was carried out as recommended in the OECD guidelines 1981...."); diet supplementation with ascorbic acid is equivocal; no details on the pilot/range finder
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
When this study was performed in 1985, the LLNA did not yet exist.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Physical state: powder
- Analytical purity: commercial grade
- Batch No.: EN 94903.52
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in-house breeding
- Age at study initiation: about 10 weeks
- Weight at study initiation: 303-426 g
- Housing: individually
- Diet (ad libitum): standard guinea pigs pellets - NAFAG No. 846, Gossau SG
- Water (ad libitum): fresh water, supplemented with fresh carrots
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: sesame oil (intradermal induction), vaseline (epicutaneous application)
Concentration / amount:
intradermal induction: 1%
epicutaneous induction: 30% (about 0.4 g/patch)
challenge: 10% (about 0.2 g/patch)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: sesame oil (intradermal induction), vaseline (epicutaneous application)
Concentration / amount:
intradermal induction: 1%
epicutaneous induction: 30% (about 0.4 g/patch)
challenge: 10% (about 0.2 g/patch)
No. of animals per dose:
10 males and 10 females
Details on study design:
RANGE FINDING TESTS: The concentrations of the test compound for induction and challenge periods were determined on separate animals (no further information).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal exposure (Day 1) and 1 epicutaneous exposure (one week later)
- Exposure period: Day 1: 2 intradermal injections; Readings: 24 hours after the beginning of application. After one week: 48 hours epicutaneous exposure.
- Test groups: Intradermal: Each two injections: A) front row: 0.1 ml mixture adjuvant and saline; B) middle row : 0.1 ml of the test substance formulation in sesame oil; C) back row : 0.1 ml of the test substance formulation in the adjuvant saline mixture
Epicutaneous: about 0.4 g of the test substance incorporated in vaseline under an occlusive dressing, duration of exposure 48 hours; Readings 48 hours after the beginning of application. The application sites were pretreated the day before with 10% sodium lauryl sulfate (open application).
- Control group: Intradermal: same injections (A, B, C) but without test substance. Epicutaneous: Animals were treated analogously to the test group, but only with the solvent.
- Site: neck
- Frequency of applications: 2 intradermal injections and 1 epicutaneous exposure (see above)
- Duration: Day 1 (intradermal injection) – after one week (epicutaneous exposure)
- Concentrations: 1 % of the test substance with intradermal induction; 30 % of the test substance with epicutaneous application

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 days after intradermal injection
- Exposure period: 24 hours
- Test groups: about 0.2 g of the test substance (flank) under an occlusive dressing.
- Control group: animals were treated with the vehicle as well as with the test compound to control the maximal subirritant concentration of the test compound in adjuvant treated animals (no further information).
- Site: flank (the application sites where chemically depilated 3 hours before examination (Veet, about 5 minutes))
- Concentrations: 10 % of the test substance
- Evaluation (hr after challenge): 24, 48 hours after removal of the patch

OTHER: The test was carried out according to the maximization test of Magnusson and Kligman (J. invest. Dermatol. 52, 268-276, 1969).
Positive control substance(s):
yes
Remarks:
p - phenylenediamine

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

After occlusive epicutaneous administration, no skin reactions were found in the control and test groups.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information