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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:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed in 1997 and thus predates the adoption of OECD Guideline 429.

Test material

Constituent 1
Test material form:
liquid: viscous
Details on test material:
- Substance type: Technical product.
- Storage condition of test material: No data.
- Concentration information of the constituents: no data

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, England.
- Weight at study initiation: 377-431 g
- Fasting period before study: 18-19 hours prior to dosing until 5.5-6 hours after dosing.
- Housing: stainless steel wire cages with five animals per cage.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: six days.

ENVIRONMENTAL CONDITIONS
- Temperature: 18.5-21°C.
- Humidity: 36-62%.
- Air changes: approximately 15 air changes per hour.
- Photoperiod: 12 hours light / 12 hours dark.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: See 'Concentration'
Concentration / amount:
Induction intradermal injection: 7.5% w/v in Alembicol D (product of coconut oil, supplied by Alembic products, Saltney, Chester, England).
Induction topical application: 33.3% w/v in Alembicol D.
Challenge application: 33.3 and 16.65% w/v in Alembicol D.
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
other: See 'Concentration'
Concentration / amount:
Induction intradermal injection: 7.5% w/v in Alembicol D (product of coconut oil, supplied by Alembic products, Saltney, Chester, England).
Induction topical application: 33.3% w/v in Alembicol D.
Challenge application: 33.3 and 16.65% w/v in Alembicol D.
No. of animals per dose:
Twenty test and ten control guinea-pigs.
Details on study design:
RANGE FINDING TESTS: The intradermal and topical irritancy of a range of dilutions of the test substance was investigated to identify a concentration of the test substance that would produce irritation suitable for the induction phase and a maximum non-irritant concentration for the challenge phase.

A. INDUCTION EXPOSURE
- Test animals: Three pairs of intradermal injections (0.1 ml) were made into a 20x40 mm area:
1. Freund's complete adjuvant (FCA)
2. Test substance 7.5% w/v in Alembicol D
3. Test substance 7.5% w/v in a 50:50 mixture of FCA and Alembicol D
Six days after the injections the same site was pre-treated with 0.5 ml of 10% w/w sodium lauryl sulphate in petrolatum. Twenty-four hours later a 20x40 mm patch was saturated with approximately 0.4 ml of the test substance, 33.3% w/v in Alembicol for 48 hours.

- Control animals: The control animals were treated similarly to the test animals with the exception that the test substance was omitted from the intradermal injections and topical application.

B. CHALLENGE EXPOSURE
- Control and test animals: Both the control and test animals were challenged with 2-amylanthraquinone.
- No. of exposures: one.
- Day(s) of challenge: two weeks after the topical induction.
- Exposure period: 24 hours.
- Site: a 20 x 20 mm area on the anterior and posterior site of the left flank.
- Concentrations: 33.3% (anterior site) and 16.64% (posterior site) in Alembicol D.
- Evaluation (hr after challenge): 24 and 48 hours.
Positive control substance(s):
yes
Remarks:
The sensitivity of the guinea-pig strain used is checked periodically with known sensitisers hexyl cinnamic aldehyde, benzocaine and 2-mercaptobenzothiazole.

Results and discussion

Positive control results:
The positive control substances all induced a sensitising effect after challenge.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
33.3% and 16.65%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of ill health or toxicity were recorded
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 33.3% and 16.65%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No signs of ill health or toxicity were recorded.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
33.3% and 16.65%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of ill health or toxicity were recorded
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 33.3% and 16.65%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No signs of ill health or toxicity were recorded.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
33.3% and 16.65%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No signs of ill health or toxicity were recorded
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 33.3% and 16.65%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No signs of ill health or toxicity were recorded.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
33.3% and 16.65%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No signs of ill health or toxicity were recorded
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 33.3% and 16.65%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No signs of ill health or toxicity were recorded.

Applicant's summary and conclusion

Interpretation of results:
other: not classified under Regulation 1272/2008/EC
Conclusions:
Based on the results of a GLP-compliant guideline study, 2-amylanthraquinone is considered to be not sensitizing to skin.
Executive summary:

Sensitizing potential of 2-amylanthraquinone was examined in the Guinea pig maximization test using twenty test and ten control guinea-pigs. After intradermal induction exposure to 2-amylanthraquinone (7.5% w/v) and induction topical application (33.3% w/v), the animals were subjected two weeks later to a challenge exposure (concentration 33.3% (anterior site) and 16.64% (posterior site)). Skin reactions were evaluated 24 and 48 hours after the end of exposure period. Since no animal showed an allergic response, the test substance is considered to be non sensitizing to skin.