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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:
guideline study with acceptable restrictions
Justification for type of information:
see section 13

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, 1959, the US Association of Food and Drug Officials
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An in vitro or in chemico skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Test material

Constituent 1
Reference substance name:
Similar Substance 02
Molecular formula:
n.a
IUPAC Name:
Similar Substance 02

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age: 10 weeks old
- Body weight: 270 - 360 g.
- Accommodation: individually in Macrolon type-3 cages
- Diet: pelleted standard NAFAG N. 830 (Gossau SG) ad libitum, supplemented with fresh carrots.
- Acclimatation: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 1 °C
- Relative humidity: 55 ± 5 %
- 14 hours light cycle day

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1 % solution of test substance in physiological saline (0.1 ml)
Day(s)/duration:
3 weeks
Challengeopen allclose all
No.:
#1
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1 ml of freshly prepared 0.1 % solution of test substance in physiological saline
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
1 %
Day(s)/duration:
24 hours
No. of animals per dose:
10 males and 10 females
Details on study design:
During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections. One control group was treated with the vehicle alone ("negative control"). On the first day, injections of 0.1 ml were administered into the shaven skin of the right flank and the back, while on the following days a single intracutaneous injection was given into the back.
During the second and third week of the induction period the test material was incorporated in a mixture of the normal vehicle with complete Bacto Adjuvant (vehicle : adjuvant = 1 : 1).
Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1 % solution was administered into the skin of the left flank.
Twenty-four hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded. The two largest perpendicular diameters (in mm) and the increase in the skin-fold thickness (in mm) were measured and by multiplication of these values "reaction volume was obtained (in pi) for each reading from each animal.
The mean volume plus one standard deviation of the induction reactions observed in the individual animal in the first week was taken as representing the skin irritation "threshold" for each animal. Any challenge reaction greater than this threshold value in the induction period was graded as an allergic reaction and the animal termed "positive". The number of "positive" animals in the test group was compared with the number of animals in the control group (treated with thevehicle alone) that showed a non-specific reaction of at least the same magnitude ("negative control").Ten days after the intracutaneous challenge injection a subirritant dose of the test compound (1 % in vaseline) was applied epicutaneously under occlusive dressings which were left in place for 24 hours. The reactions were evaluated 24 h after removing of the bandages according the Draize scoring scale.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
10
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: not reported

Any other information on results incl. tables

No animals gave positive reactions after occlusive epicutaneous application

Under the experimental conditions employed, significant differences between the test group and the vehicle treated controls were only seen after intradermal challenge application of test item, i.e. when the skin barrier was intentionally by-passed. No difference between the test and the control group was seen after epidermal challenge application. The negative results upon epidermal challenge demonstrate that, in artificially sensitized guinea-pigs, exposure of the intact skin to the test compound does not provoke contact dermatitis.

Applicant's summary and conclusion

Interpretation of results:
other: skin sens 1A (H317), according to the CLP Regulation
Conclusions:
Under the experimental conditions, 50 % of the animals of the test group were sensitised after intradermal challenge injection. No animals gave positive reactions after occlusive epicutaneous application.
Executive summary:

The skin sensitisation potential was evaluated using an intracutaneous sensitization procedure similar to the method reccomended in the Appraisal of the safety of chemicals in Foods, Drug and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO).

Under the experimental conditions, 50 % of the animals of the test group were sensitised after intradermal challenge injection.

Whereas, no animals gave positive reactions after occlusive epicutaneous application.

Therefore, according to the CLP Regulation (EC n. 1272/2008), the substance is classified as skin sensitiser, category 1A, since in the Guinea pig maximisation test the response in more than 30 % of the animals was positive, responding at ≤ 0,1 % intradermal induction dose.

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