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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:
comparable to guideline study with acceptable restrictions
Remarks:
no detailed data about induction conditions

Data source

Reference
Reference Type:
publication
Title:
A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test.
Author:
Nakamura A, Momma, Sekiguchi H, Noda T, Yamano T, Kaniwa MA, Kojima S, Tsuda M abd Kurokawa Y.
Year:
1994
Bibliographic source:
Contact Dermatitis 1994 ; 31 : 72-85.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: Magnusson and Kligman J. Invest. Dermatol 1969 ; 52 : 268-276
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An old GPMT was available in the publication. No new study was performed for skin sensitisation endpoint for REACH regulation.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
no data

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: olive oil (intradermal induction), petrolatum (topical induction) and acetone (challenge)
Concentration / amount:
Induction / intradermal injection : 0, 2, 20, 200, 2000 ppm
Induction / topical : 0, 250 000 ppm
Challenge / topical : 0, 0.2, 2, 20, 200, 2000 ppm
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: olive oil (intradermal induction), petrolatum (topical induction) and acetone (challenge)
Concentration / amount:
Induction / intradermal injection : 0, 2, 20, 200, 2000 ppm
Induction / topical : 0, 250 000 ppm
Challenge / topical : 0, 0.2, 2, 20, 200, 2000 ppm
No. of animals per dose:
10 per group
Details on study design:
Challenge : On day 22, all the animals received a topical open application of 0.1 ml of the test substance in their right flank (while their left flank received the vehicle).
- Clinical examinations: no
- Mortality: no
- Body weight: no
- Necropsy: no
Challenge controls:
no
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Group:
negative control
Dose level:
no induction
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No effects with a challenge of 0 - 0.2 - 2 - 20 - 200 and 2000 ppm
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction of 2 ppm
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No effects at challenge concentrations (0 - 0.2 - 2 - 20 - 200 and 2000 ppm)
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
intradermal induction of 20 ppm
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No effects at challenge concentration of 0 - 0.2 - 2 and 20 ppm
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
intradermal induction of 20 ppm
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
at challenge concentrations of 200 ppm
Reading:
1st reading
Group:
test group
Dose level:
intradermal Induction of 20 ppm
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
At challenge concentration of 2000 ppm
Reading:
1st reading
Group:
test group
Dose level:
Interdermal induction of 200 ppm
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No effects at challenge concentration of 0 - 0.2 - 2 - 20 ppm
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal concentration of 200 ppm
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
at challenge concentration of 200 ppm
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction of 200 ppm
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
At challenge concentration of 2000 ppm
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction of 2000 ppm
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No effects at challenge concentrations of 0 - 0.2 and 2 ppm
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction of 2000 ppm
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
at challenge concentration of 20 ppm
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction of 2000 ppm
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
At challenge concentration of 200 ppm
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction of 2000 ppm
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
At challenge concentration of 2000 ppm
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

No redness was observed in the control animals (in animals not induced but challenged, and in animals not induced and not challenged).

In the test groups (induced and challenged), a positive effect (redness in more 30% of animal) was observed at the induction concentration of 200 ppm (0.02%) at 200 and 2000 ppm of challenge doses (60 and 80% respectively).

This positive effect was confirmed at the induction concentration of 2000 ppm.

DBTU is a skin sensitizer according to this GPMT test.

Applicant's summary and conclusion

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
According this Guinea pigs maximalisation test, DBTU is a skin sensitizer .
Executive summary:

A guinea pigs maximalisation test was performed according to the Magnuson and Kligman method with DBTU.

In induction phase, guinea pigs were exposed by intradermal injection (0, 2, 20, 200, 2000 ppm of DBTU) and by topical administration (250 000 ppm of DBTU).

In the challenge phase, animals were exposed by topical administration at : 0, 0.2, 2, 20, 200 or 2000 ppm of DBTU.

No redness was observed in the control animals (in animals not induced but challenged, and in animals not induced and not challenged).

In the test groups (induced and challenged), a positive effect (redness in more 30% of animal) was observed at the induction concentration of 200 ppm (0.02%) at 200 and 2000 ppm of challenge doses (60 and 80% respectively).

This positive effect was confirmed at the induction concentration of 2000 ppm.

DBTU is a skin sensitizer according to this GPMT test.