Registration Dossier

Administrative data

Description of key information

To assess the allergenic potential of the test article in albino guinea pigs the Maximization-Test (OECD guideline 406) was used. None of the animals showed erythema or oedema after multiple treatments with the test article. Therefore, the test substance is considered to be a non-sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
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.
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
Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
Intradermal induction exposure: 5%
Epicutaneous induction and epicutaneous challenge exposure (based on pretest results): 40%
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.
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.
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
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Procedure and observations

To assess the allergenic potential of the test article in albino guinea pigs the Maximization-Test (OECD guideline 406) was used (Ciba 1992e). Ten animals per sex were used in the treatment group, five of each in the control group. After intradermal and epicutaneous induction, the animals were challenged epicutaneous with a 40% solution of the substance in petrolatum. Evaluation and scoring of the reactions followed after 24h and 48h. Positive controls were performed with potassium dichromate.

None of the animals showed erythema or oedema after treatment with the test article. Neither toxic symptoms nor deaths occurred in the control and test groups.

 

Discussion

Multiple application of the test substance onto skin did not cause an allergic reaction. Therefore, the test substance is considered to be a non-sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin sensitization under Directive 67/548/EEC,as amended for the 30th time in Directive 2008/58/EC.

                               

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC 944/2013.