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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:
10.11.2003 - 5.12.2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
(3S,5S)-5-[(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl]-3-(propan-2-yl)oxolan-2-one
EC Number:
608-748-5
Cas Number:
324763-46-4
Molecular formula:
C25 H39 N3 O5
IUPAC Name:
(3S,5S)-5-[(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl]-3-(propan-2-yl)oxolan-2-one

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: albino
Sex:
male/female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal: olive oil, epicutaneous (induction and challenge): vaseline
Concentration / amount:
Induction - intradermal: 10% test substance in olive oil
Induction - topical application: 50 % test substance in vaseline
Challenge - topical application: 0.5% and 1 % test substance in vaseline
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: intradermal: olive oil, epicutaneous (induction and challenge): vaseline
Concentration / amount:
Induction - intradermal: 10% test substance in olive oil
Induction - topical application: 50 % test substance in vaseline
Challenge - topical application: 0.5% and 1 % test substance in vaseline
No. of animals per dose:
treatment group: 10 (4 males and 6 females), control group: 5 (2 males and 3 females)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single intradermal injection on Day 0 and 48 h epicutaneous treatment on Day 6
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/olive oil
Injection 2: 10% of test substance in olive oil
Injection 3: 10% of test substance in a 1:1 mixture (v/v) FCA/olive oil

Epicutaneous: 50% of the test substance in vaseline (24 h before, the skin was pre-treated with 10% sodium lauryl sulphate in vaseline)

- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/olive oil
Injection 2: olive oil
Injection 3: olive oil in a 1:1 mixture (v/v) FCA/olive oil

Epicutaneous: vaseline (24 h before, the skin was pre-treated with 10% sodium lauryl sulphate in vaseline)

- Site: shoulder region (intradermal and epicutaneous, respectively)
- Frequency of applications: on Days 0 and 6
- Concentrations: intrdermal 10%, epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 20
- Exposure period: 24 h
- Site: one flank
- Concentrations: 0.5 and 1%
- Evaluation (hr after challenge): 48 and 72 h
Positive control substance(s):
yes
Remarks:
benzocaine

Results and discussion

Positive control results:
The reliability of the experimental technique was checked in intervals of approximately 6 months by testing the positive control substance benzocaine. At the last experiment in August 2003, the positive control substance induced positive reactions in 5/10 animals (50%), thus meeting the reliability criteria for the GPMT test.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5% test substance in vaseline
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical observations
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no clinical observations.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5% test substance in vaseline
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
no clinical observations
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% test substance in vaseline. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: no clinical observations.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0.5% test substance in vaseline
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical observations
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0.5% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no clinical observations.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
0.5% test substance in vaseline
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical observations
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.5% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no clinical observations.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to REGULATION (EC) No 1272/2008 (CLP) the test substance has to be classified as a skin sensitizer.