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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:
30 August 1999 - 8 October 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
STI571 Y5A
IUPAC Name:
STI571 Y5A
Constituent 2
Chemical structure
Reference substance name:
3-Dimethylamino-1-(3-pyridinyl)-2-propen-1-one
Cas Number:
55314-16-4
Molecular formula:
C10 H12 N2 O
IUPAC Name:
3-Dimethylamino-1-(3-pyridinyl)-2-propen-1-one
Details on test material:
- Physical state: Brown solid
- Analytical purity: 98.6%
- Lot/batch No.: 992301
- Expiration date of the lot/batch: 01 July 2001
- Storage condition of test material: In refrigerator in the dark

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
induction intradermal 20%
induction epidermal 50%
challenge: 0 and 50%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
induction intradermal 20%
induction epidermal 50%
challenge: 0 and 50%
No. of animals per dose:
Experimental group: 10 females.
Control group : 5 females.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no.
Reading:
2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
no
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: no.
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
no
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: no.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no.

In vivo (LLNA)

Results
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Not applicable (no LLNA test)

Any other information on results incl. tables

During the challenge phase skin reactions varying between grades 2 and 3 were observed in all experimental animals in response to the 50% test substance concentration. No skin reactions were evident in the control animals. Eschar formation and fissuring of the skin was seen in some treated skin sites among the experimental animals.

No mortality occurred and no symptoms of systemic toxicity were observed in the animals of the main study.

Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The skin reactions observed in response to a 50% test substance concentration in ten (of the ten) experimental animals in the challenge phase were considered indicative of sensitisation, based on the absence of any response in the control animals.
These results indicate a sensitisation rate of 100 per cent.
Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), STI571 Y5A should be labelled as: may cause sensitisation by skin contact (R 43) and according CLP EEC 1272/2008 classified as skin sensitizer, Category 1.