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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
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report which meets basic scientific principles. Values for positive control substances not reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The optimisation test (Maurer, Th., Thomann, P., Weirich, E.G. and Hess, R. (1975) The Optimisation test in the guinea pig. A method for the predictive evaluation of the contact allergenicity of chemicals. Agents and Actions Vol. 5 (2), 174-179, 1975) was used, an intracutaneous sensitization procedure similar to the method recommended in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).
GLP compliance:
no
Type of study:
Maurer optimisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate
EC Number:
264-513-3
EC Name:
Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate
Cas Number:
63843-89-0
Molecular formula:
C42H72N2O5
IUPAC Name:
bis(1,2,2,6,6-pentamethylpiperidin-4-yl) butyl(3,5-di-tert-butyl-4-hydroxybenzyl)malonate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: solid
- Analytical purity: no data provided
- Lot/batch No.: EN 6398

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: bred on own premises
- Weight at study initiation: 400 - 450 g
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 14/10

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: polyethylenglycol (PEG) 400 + saline (70:30)
Concentration / amount:
intradermal: 0.1%
epicutaneous: 50%
Challengeopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: polyethylenglycol (PEG) 400 + saline (70:30)
Concentration / amount:
intradermal: 0.1%
epicutaneous: 50%
No. of animals per dose:
10 female and 10 male
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % dilution in polyethylene glycol (PEG 400) + saline (70 : 30 parts). 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).

B. CHALLENGE EXPOSURE
Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1 % dilution of the test substance in polyethylene glycol (PEG 400) + saline (70 : 30 parts) 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. Before examination, the reaction sites were depilated chemically (Butoquick®, 5 minutes).

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 µl) 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 the vehicle 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 was applied epicutaneously under occlusive dressings which were left in place for 24 hours.

Study design: in vivo (LLNA)

Statistics:
The exact Fisher test for comparison of the basic probability of two binominal distributions; L. Sachs, Statistische Auswertungsmethoden, Thieme Verlag, Stuttgart, 1971. A probability of p ≤ 0.01 was considered to indicate a significant difference.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

A) Incidence of positive animals per group after intradermal challenge injection:

   No. of positive animals/ No. of treated animals  P
 Vehicle control  1/20  0.75
 Test substance  12/20  < 0.001

B) Incidence of positive animals per group after occlusive epicutaneous application

   No. of positive animals/ No. of treated animals  P
 Vehicle control  0/20  -
 Test substance  0/20  -

C) Challenge reactions after occlusive epicutaneous administration of the test compound

Erythema score (Draize Score) 24 hours after removal of the dressing.

 Animal No.  male  1 2 10 
 Erythema Score     0  0  0  0
 Animal No.  female 11  12  13  14  15  16  17  18  19  20 
Erythema Score      0  0  0  0  0  0 0  0  0

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information

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