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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

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 study and an old LLNA were available in the litterature before REACH registration. No new study were performed on skin sensitisation endpoint to fill the REACH dossier.

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
Vehicle:
other: olive oil
Concentration / amount:
0, 20, 200, 2000, 20000 ppm
Route:
epicutaneous, open
Vehicle:
other: petrolatum
Concentration / amount:
0, 250000 ppm
Challenge
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: acetone
Concentration / amount:
0, 2, 20, 200, 2000 ppm
No. of animals per dose:
2-10 per group
Details on study design:
Study protocol :
According to the method of Magnusson and Kligman (Magnusson B, Kligman AM. The identification of contact allergens by animal assay. The guinea pig maximization test. J Invest Dermatol 1969: 52: 268 -276.),a surface of 8 cm² (2x4 cm) was exposed to DETU.

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
Positive control substance(s):
yes
Remarks:
but not concomitant

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:
7
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 (20 ppm)
No. with + reactions:
0
Total no. in group:
7
Clinical observations:
challenge concentrations =0, 2, 20, 200 or 2000 ppm
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction (200 ppm)
No. with + reactions:
0
Total no. in group:
7
Clinical observations:
challenge concentrations =0, 2, 20, 200 or 2000 ppm
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction (2000 ppm)
No. with + reactions:
0
Total no. in group:
7
Clinical observations:
challenge concentrations =0 or 2 ppm
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction (2000 ppm)
No. with + reactions:
3
Total no. in group:
7
Clinical observations:
Challenge concentration = 20 ppm
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction (2000 ppm)
No. with + reactions:
4
Total no. in group:
7
Clinical observations:
challenge concentrations = 200 or 2000 ppm
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction (20 000 ppm)
No. with + reactions:
2
Total no. in group:
7
Clinical observations:
challenge concentrations = 2 ppm
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction (20 000 ppm)
No. with + reactions:
4
Total no. in group:
7
Clinical observations:
challenge concentrations =20 ppm
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Group:
test group
Dose level:
Intradermal induction (20 000 ppm)
No. with + reactions:
7
Total no. in group:
7
Clinical observations:
challenge concentrations = 200 or 2000 ppm
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Group:
positive control
No. with + reactions:
7
Total no. in group:
7
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

Below 2000 ppm no cutaneous reactions were observed after the challenge application.
In the animals induced by an injection of 2000 ppm, 3/7 of those challenged by 20 ppm, 4/7 of those challenged by 200 ppm and 4/7 of those challenged by 2000 ppm displayed a positive reaction. Mean response were respectively 0.4, 0.7 and 0.8.
In animals induced by an injection of 20000 ppm, 2/7 of those challenged by 2 ppm, 4/7 of those challenged by 20 ppm, 7/7 of those challenged by 200 ppm and 7/7 of those challenged by 2000 ppm had a positive reaction. 
Mean response were respectively 0.3, 0.6, 1.6 and 2.0.

 

Applicant's summary and conclusion

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

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

In induction phase, guinea pigs were exposed by intradermal injection (0, 20, 200, 2000, 20000 ppm of DETU) and by topical administration (0 or 250 000 ppm of DETU). In the challenge phase, animals were exposed by topical administration at : 0, 20, 200, 2000 or 20000 ppm of DETU.

Below 2000 ppm (induction phase) no cutaneous reactions were observed after the challenge application.
In the animals induced by an injection of 2000 ppm, 3/7 of those challenged by 20 ppm, 4/7 of those challenged by 200 ppm and 4/7 of those challenged by 2000 ppm displayed a positive reaction. Mean response were respectively 0.4, 0.7 and 0.8.
In animals induced by an injection of 20000 ppm, 2/7 of those challenged by 2 ppm, 4/7 of those challenged by 20 ppm, 7/7 of those challenged by 200 ppm and 7/7 of those challenged by 2000 ppm had a positive reaction. 
Mean response were respectively 0.3, 0.6, 1.6 and 2.0.

 According this Guinea pigs maximalisation test, DETU is a skin sensitizer .