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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Contact allergy to colour developing agents in the guinea pig.
Author:
Liden, C. and Boman, A.
Year:
1988
Bibliographic source:
Contact Dermatits 19: 290-295

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
not specified
Principles of method if other than guideline:
The test was performed in 1988 according to the procedure described by Magnusson & Klingman 1969 when the OECD Guideline 406 adopted 1981 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) was considered acceptable.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was done before LLNA as first-choice method for in-vivo testing was set into force.

Test material

Reference
Name:
Unnamed

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: JA Sahlin, Malmo, Sweden

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
initial test: 0.25% intradermally and 20% in water topically
Day(s)/duration:
initial test: intradermal induction on day 0, topical induction on day 6, challenge on day 21
Adequacy of induction:
other: moderate irritant concentration
Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
final test: 0.2% intradermally and 25% in petrolatum topically
Day(s)/duration:
final test: intradermal induction on day 0, topical induction on day 7, challenge on day 21
Adequacy of induction:
other: moderate irritant concentration
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: saline
Concentration / amount:
initial test: 1%
Day(s)/duration:
challenged on day 21; reactions read 48 and 72 h after application
Adequacy of challenge:
other: non-irritant concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
final test: 0.5 and 0.1 mol/kg in petrolaum
Day(s)/duration:
challenged on day 21; reactions read 48 and 72 h after application
Adequacy of challenge:
other: non-irritant concentration
No. of animals per dose:
21 animals in the initial test; 20 animals in the final test
Details on study design:
RANGE FINDING TESTS: Pre-testing for irritancy was carried out with separate animals using dilutions with both water and petroleum to establish concentrations at which moderate irritation and no irritation occured. These concentrations were used to determine the induction (moderate irritation) and challenge (no irritation) concentrations.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: One intradermal and one topical exposure
- Exposure period: initial test: intradermal induction on day 0, topical induction on day 6, challenge on day 21; final test: intradermal induction on day 0, topical induction on day 7, challenge on day 21
- Test groups: initial test: 21 treated animals and 21 negative control animals; final test: 20 treated animals and 20 negative control animals
- Control group: yes; saline and petrolatum
- Site: not reported
- Frequency of applications: the induction period consisted of 2 exposures
- Duration: initial test: intradermal induction on day 0, topical induction on day 6, challenge on day 21; final test: intradermal induction on day 0, topical induction on day 7, challenge on day 21
- Concentrations: initial test: 0.25% intradermally and 20% in water topically; final test: 0.2% intradermally and 25% in petrolatum topically

B. CHALLENGE EXPOSURE
- No. of exposures: One topical exposure
- Day(s) of challenge: challenged on day 21
- Exposure period: challenged on day 21; reactions read 48 and 72 h after application
- Test groups: initial test: 21 treated animals and 21 negative control animals; final test: 20 treated animals and 20 negative control animals
- Control group: yes; saline and petrolatum
- Site: not reported
- Concentrations: initial test: 1%; final test: 0.5 and 0.1 mol/kg in petrolaum
- Evaluation (hr after challenge): reactions read 48 and 72 h after application
Challenge controls:
Saline and petrolatum
Positive control substance(s):
no

Results and discussion

Positive control results:
Not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
initial test: 1% in saline
No. with + reactions:
6
Total no. in group:
21
Clinical observations:
not reported
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
other: solvent control
Dose level:
initial test: saline
No. with + reactions:
0
Total no. in group:
21
Clinical observations:
not reported
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
final test: 0.5 mol/kg in petrolatum
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
not reported
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
final test: 0.1 mol/kg in petrolatum
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
not reported
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
other: solvent control
Dose level:
final test: petrolatum
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
not reported
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

The 48 hour readings were reported without the 72 hour readings because there were only minor variations without statistically significant differences.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS Category 1 (H317) according to Regulation (EC) No 1272/2008
Conclusions:
In a published guinea pig maximization test, guinea pigs were induced with 0.25% CD-3 intradermally and 20% CD-3 in water topically in an initial test. Animals were then challenged with 1% of CD-3. In the final test, animals were induced with 0.2% CD-3 intradermally and 25% CD-3 in petrolatum topically. Animals were then challenged topically with 0.5 and 0.1 mol/kg in petrolaum. Results from the initial test showed that 6/21 animals showed a positive response to CD-3 at the 48 hour observation. All animals (n=20) in the final test showed sensitization for both dose levels. Based on these results, CD-3 was established as a skin sensitizer.