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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
Study period:
1989-01-18 till 1989-02-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD) with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(adopted 1981)
GLP compliance:
yes
Remarks:
(BASF AG, Department of Toxicology )
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trioxan-Schuppen
- Physical state: solid, crystalline, white
- Analytical purity: 99.9%
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagermann GmbH & Co.
- Weight at study initiation: 259-319 g
- Housing: 5 per cage
- Diet (e.g. ad libitum): Kliba 341.4 mm (Klingentalmühle AG, Kaiseraugst)
- Water (e.g. ad libitum): tap water, addition of about 2g ascorbic acid/10 L water twice every week
- Acclimation period: at least 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
PRETEST
- The animals were exposed to about 0.15 g of the test substance formulation applied to the skin under occlusive conditions

MAIN TEST
- Intradermal induction: 5% test substance formulation in either aqua dest. or Freund's adjuvant/ aqua dest. (1:1)
- Epicutaneous induction: 50% test substance formulation in either aqua dest.
- First Challenge: 50% test substance formulation in either aqua dest.
- Second Challenge: 50% test substance formulation in either aqua dest.

Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
PRETEST
- The animals were exposed to about 0.15 g of the test substance formulation applied to the skin under occlusive conditions

MAIN TEST
- Intradermal induction: 5% test substance formulation in either aqua dest. or Freund's adjuvant/ aqua dest. (1:1)
- Epicutaneous induction: 50% test substance formulation in either aqua dest.
- First Challenge: 50% test substance formulation in either aqua dest.
- Second Challenge: 50% test substance formulation in either aqua dest.

No. of animals per dose:
20 animals in the test group
10 animals in each of two control groups
Details on study design:
PRETEST
- No. of exposures: 2 times for 24 hours within a period of 96 hours (about 0.15 g of the test substance formulation under occlusive condition)
- Exposure period: 24h
- Test groups: 4 animals per test concentration
- Site: Flank, second application on the same spot
- Frequency of applications: 24h after initial application, second application was administered
- Reading: about 24h and 48h after the begining of application (assessment of skin findings)
- Duration: 96h

MAIN STUDY

INDUCTION
Intradermal Application
- No. of exposures: 6 intradermal injections in groups of two per animal
- Exposure period: 24h
- Test groups: 20 animals
- Control group: 10 animals
- Site: Shoulder
- Frequency of applications: one time
- Concentrations: 2 injections each of 0.1 ml Freund's adjuvant without test substance emulsified with water (1:1) followed by 2 injections each of 0.1 ml of the test substance formulation, followed by 2 injections each of 0.1 ml Freund's adjuvant/water (1:1) with test substance in the test group. Control group were given the same injections but without test substance, only with the formulating agent.

Percutaneous Application
- Time of application: one week after intradermal application
- No. of exposures: single dermal application
- Exposure period: 48h
- Test groups: 20
- Control group: 10
- Site: Shoulder, same area as preceding intradermal application
- Frequency of applications: one time
- Concentrations: The test animals were exposed to about 50% test substance formulation in aqua dest (0.3 g of the test substance formulation) under an occlusive dressing. The control animals were treated since with distilled water in similar manner.

CHALLENGE
Two challenges were conducted:
- First challenge: treatment of the test group and of control group 1 with the test substance formulation (control group 2 remained untreated);
- Second challenge: treatment of the test group and of control groups 1 and 2 with the test substance formulation
- Day(s) of challenge: (first challenge: 14d after percutaneous exposure, second challenge: 7d after first challenge)
- Exposure period: 24h
- Test groups: 20
- Control group: 10
- Site: Intact clipped flank
- Concentrations: The test animals were exposed to about 50% test substance formulation in aqua dest under an occlusive dressing.
- Evaluation (hr after challenge): 24, 48 and 72h after begin of application
Challenge controls:
10 guinea pigs
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
50% test substance in aqua dest.
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% test substance in aqua dest.. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% test substance in aqua dest.
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% test substance in aqua dest.. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
50% test substance in aqua dest.
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50% test substance in aqua dest.. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
50% test substance in aqua dest.
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% test substance in aqua dest.. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
No test substance application
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: No test substance application. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Skin irritation findings during induction:

After intradermal induction, distinct erythema and edema were observed at the injection sites of both control and test animals, at which only Freund's adjuvant/aqua dest. (1:1) was applied. Injection of test substance preparation in aqua dest caused distinct erythema in the test animals. The application areas which were injected with test substance preparation in Freund's adjuvant/aqua dest. (1:1) exhibited distinct erythema and edema. The control animals injected with aqua dest. (vehicle) did not show any skin reactions.

 

Result of the maximization test:   

No skin reactions could be observed in the control and treated groups after both, the first and the second challenge.

Applicant's summary and conclusion