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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:
1992-08-11 - 1992-11-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The GPMT has been carried out as an animal test to predict human sensitisation for over a decade and is recommended by international test guidelines such as OECD.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited Animal Production, Stein, Switzerland
- Age at study initiation: young adult based on body weight range
- Weight at study initiation: 334 to 414 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets, ad libitum
- Water: fresh water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30 - 70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 1992-09-07 To: 1992-10-08

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
Intradermal induction exposure: 5%
Epicutaneous induction and epicutaneous challenge exposure (based on pretest results): 40%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Intradermal induction exposure: 5%
Epicutaneous induction and epicutaneous challenge exposure (based on pretest results): 40%
No. of animals per dose:
Pretest: 6 animals (3 males, 3 females)
Main test: 20 test animals (10 males, 10 females), 10 control animals (5 males, 5 females),
Details on study design:
RANGE FINDING TESTS:
A pretest was performed to identify appropriate test item concentrations for induction and challenge in the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 exposures, i.e. a single intradermal exposure in week 1 (6 injections/animal) and an epicutaneous exposure in week 2 (closed patch)
- Exposure period: single application (intradermal exposure), 48 hours (epicutaneous exposure)
- Test group: 1 group of 20 animals
- Control group: 1 group of 10 animals
- Site: neck region
- Frequency of applications: 1 intradermal application (week 1) and 1 epicutaneous application (week 2)
- Concentrations: 5 % (intradermal exposure), 40 % (epicutaneous exposure)

B. CHALLENGE EXPOSURE
- No. of exposures: 1 epicutaneous exposure
- Day of challenge: in week 5 of the study period
- Exposure period: 24 hours
- Test group: 1 group of 20 animals
- Control group: 1 group of 10 animals
- Site: neck region
- Concentration: 40 % (epicutaneous exposure)
- Evaluation: approximately 24 and 48 hours after removal of the dressing

OTHER:
No skin irritation was observed in the pretest. Therefore the application site was pretreated with 10 % sodium laurylsulfate (open application) 24 hours prior to the epidermal induction application.
Challenge controls:
No evident positive reactions were noted after the first challenge application, neither when treated with vaseline alone nor when treated with a 40% test substance dilution.
Positive control substance(s):
yes
Remarks:
Potassiumdichromate, for the induction period a 0.20 % dilution in physiological saline (intradermal induction) and 5 % preparation in vaseline (for epidermal induction) was used. For the challenge procedure a 1 % preparation in vaseline was used.

Results and discussion

Positive control results:
A positive control with a known sensitizer produced the expected rate of sensitization reactions and demonstrated the sensitivity of the test system.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
40 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
40 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

In a dermal sensitisation study with the test item (as described in section 1.2) in Oleum arachidis (intradermal induction) or in vaseline (epicutaneous applications), young adult guinea pigs (test group: 10 males and 10 females, control group: 5 males and 5 females) were tested using the guinea pig maximisation test of Magnusson and Kligman. In this study, the test group animals received 5 % of the test item for intradermal induction in week 1 as well as 40 % (highest non-irritant concentration) of the test item for epicutaneous induction in week 2 and challenge in week 5. Concurrent negative control animals were treated similarly, except that during the induction phase the test item was omitted. No animal of the test group was sensitised by the test item under the experimental condition employed. Under the conditions of this study, the test item was not a skin sensitiser.