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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:
weight of evidence
Study period:
From April 23 to June 15, 1979.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Internationally accepted guideline, well documented and scientifically acceptable.

Data source

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

Materials and methods

Principles of method if other than guideline:
The optimization test was used, an intracutaneous sensitization procedure exceeding the sensitivity of 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
Remarks:
Pre GLP.
Type of study:
Maurer optimisation test
Justification for non-LLNA method:
Valid test available

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: test laboratory.
- Age at study initiation: ca 10 weeks old.
- Weight at study initiation: between 280 to 390 grams.
- Housing: housed individually in Macrolon cages type 3.
- Diet: ad libitum standard guinea pig pellets - NAFAG, No. 830, Gossau SG.
- Water: ad libitum.
- Acclimation period: the animals were acclimatized for 10 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 1 °C
- Humidity: 55 ± 5 %
- Photoperiod: 14 hours light cycle day.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: intradermal: physiological saline; epidermal: vaseline PhH VI.
Concentration / amount:
0.1% for intradermal application.
30% for epidermal application.
Challengeopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal: physiological saline; epidermal: vaseline PhH VI.
Concentration / amount:
0.1% for intradermal application.
30% for epidermal application.
No. of animals per dose:
1 male and 10 female guinea pigs.
Details on study design:
A. INDUCTION EXPOSURE
- No. of exposures: one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared solution.
- Control group: one control group was treated with the vehicle alone ("negative control").
- Site: 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.

B. CHALLENGE EXPOSURE
Intradermal
- First challenge injection: fourteen days after the last sensitizing injection.
- Site: administered into the skin of the left flank.
- Observation: 24 hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded.
- Evaluation/scoring system: 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").

Epicutaneous
- Application: 10 days after the intracutaneous challenge injection.
- Dose: subirritant dose of the test compound: 30 % in vaseline.
- Route: test substance was applied epicutaneously under occlusive dressings.
- Duration/exposure: 24 hours.
- Scoring system: 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
Reading:
other: Incidence of positive animals per group after intradermal challenge injection.
Group:
test group
Dose level:
0.1 %
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
other: Reading:
Reading:
other: Incidence of positive animals per group after occlusive epicutaneous application.
Group:
test group
Dose level:
30 %
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading:

Any other information on results incl. tables

Intradermal injection of the vehicle alone failed to induce sensitization.

Incidence of positive animals per group after intradermal challenge injection.

N. of positive animals/N. treated animals P
Vehicle control 0/20
Test substance 16/20 < 0.01

Incidence of positive animals per group after occlusive epicutaneous application.

N. of positive animals/N. treated animals P
Vehicle control 0/20
Test substance 2/20 > 0.01

Challenge reactions after occlusive epicutaneous administration of the test material.

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

Animal N. males 681 682 683 684 685 686 687 688 689 690
Score 0 0 0 1 0 0 2 0 0 0
Animal N. females 691 692 693 694 695 696 697 698 699 700
Score 0 0 0 0 0 0 0 0 0 0

Reaction volumes (µl) after intradermal injection of test substance.

Animal identification number Induction (mean + s) after skin sensitization  + = positive reactor
Application N.  Mean Standard deviation
1 2 3 4
681 M 0 0 0 0 0 0 0 0 -
682 M 0 0 0 0 0 0 0 32 +
683 M 0 0 0 0 0 0 0 9 +
684 M 0 0 0 0 0 0 0 224 +
685 M 0 0 0 0 0 0 0 65 +
686 M 0 0 9 0 2.3 4.5 6.8 64 +
687 M 0 0 0 0 0 0 0 62 +
688 M 0 0 0 0 0 0 0 6 +
689 M 0 0 0 0 0 0 0 18 +
690 M 0 0 0 0 0 0 0 7 +
691 F 0 0 0 0 0 0 0 72 +
692 F 0 0 0 0 0 0 0 0 -
693 F 0 0 0 0 0 0 0 0 -
694 F 0 0 0 0 0 0 0 79 +
695 F 0 0 0 0 0 0 0 45 +
696 F 0 0 0 0 0 0 0 112 +
697 F 0 0 0 0 0 0 0 315 +
698 F 0 0 0 0 0 0 0 13 +
699 F 5 0 0 0 1.3 2.5 3.8 170 +
700 F 0 0 0 0 0 0 0 0 -
Goup mean 0.3 0 0.5 0 64.7 16/20

Reaction volumes (µl) after intradermal injection of physiological saline.

Animal identification number Induction (mean + s) after skin sensitization  + = positive reactor
Application N.  Mean Standard deviation
1 2 3 4
641 M 0 0 0 0 0 0 0 0 -
642 M 0 0 0 0 0 0 0 0 -
643 M 0 0 0 0 0 0 0 0 -
644 M 0 0 0 0 0 0 0 0 -
645 M 0 0 0 0 0 0 0 0 -
646 M 0 0 0 0 0 0 0 0 -
647 M 0 0 0 0 0 0 0 0 -
648 M 0 0 0 0 0 0 0 0 -
649 M 0 0 0 0 0 0 0 0 -
650 M 0 0 0 0 0 0 0 0 -
651 F 0 0 0 0 0 0 0 0 -
652 F 0 0 0 0 0 0 0 0 -
653 F 0 0 0 0 0 0 0 0 -
654 F 0 0 0 0 0 0 0 0 -
655 F 0 0 0 0 0 0 0 0 -
656 F 0 0 0 0 0 0 0 0 -
657 F 0 0 0 0 0 0 0 0 -
658 F 0 0 0 0 0 0 0 0 -
659 F 0 0 0 0 0 0 0 0 -
660 F 0 0 0 0 0 0 0 0 -
Goup mean 0 0 0 0 0 0/20

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Intradermal injection of the vehicle alone failed to induce sensitization.
Executive summary:

Method

The optimization test was used, an intracutaneous sensitization procedure exceeding the sensitivity of 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).

Results

Intradermal injection of the vehicle alone failed to induce sensitization.