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Diss Factsheets

Administrative data

Description of key information

In a Guinea pig skin sensitization test (Maximization test), a sensitizing potential of the test item was evident. Although a Buehler test revealed only ambigious results, the test article is considered to be a mild 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:
1995-06-12 to 1995-09-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
July 31, 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17, 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Since two valid guinea pig studies are available, no LLNA is necessary.
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, 4332 Stein / Switzerland
- Age at study initiation:
- Weight at study initiation: 344 to 409 g
- Housing: individually, in Macrolon cages (Type 3)
- Diet (ad libitum): standard guinea pig pellets - NAFAG 845, NAFAG, Gossau/SG, Switzerland
- Water (ad libitum): fresh water
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
peanut oil
Concentration / amount:
5 %
Day(s)/duration:
Day 0
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
50 %
Day(s)/duration:
Day 8
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
30 %
Day(s)/duration:
Day 21
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
- 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group
Details on study design:
RANGE FINDING TESTS:
The concentration for the epidermal applications was selected on account of the primary irritation potential of the test article.
The following concentrations of the test item were examined in pretest animals in duplicate to determine the maximum subirritant concentration: 30 and 50 % (w/v) in vaseline.

MAIN STUDY
A. INDUCTION EXPOSURE

Day 0 Induction, intradermal
- No. of exposures: Three pairs of intradermal injections (0.1 ml per injection)
- Site:o n the left and right side of the shaved neck
- Frequency of applications: consecutively
- Concentrations:Test group: - adjuvant/physiological saline mixture 1:1 (v/v)
- 5% test item in oleum arachidis
- 5% test item in the adjuvant/physiological saline mixture (w/v)
Control group: - adjuvant/physiological saline mixture 1:1 (v/v)
- adjuvant/physiological saline mixture 1:1 (v/v)
- oleum arachidis

DAY 8: INDUCTION, epidermal
In the test group the test item was suspended in vaseline and applied on a filter paper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g per patch; occlusive dressing for 48 hours).
The control group was treated with the vehicle only.

Test group: - 50 % test item in vaseline
Control group: - vaseline

Induction reactions
- Irritation was examined on day 10, 1 hour after removal of the dressing.

B. CHALLENGE EXPOSURE

- Amount: approx. 0.35 mL per chamber
- Dressing: occlusive
- Exposure period: 24 hours
- Site: both flanks
- Concentrations: Test and control group: - 30% test item in vaseline
- vaseline

- Evaluation (hr after challenge): The challenge reactions were scored 24 and 48 hours after removing the dressings according to the Draize scale
Positive control substance(s):
yes
Remarks:
once or twice a year with a known mild to moderate sensitiser, such as mercaptobenzothiazole, hexyl cinnamic aldehyde or potassiumdichromate
Positive control results:
Reference Values with 2-Mercaptobenzothiazole: The reliability check resulted in positive response in 13 (6 males and 7 females) of 20 (appr. 60 %) challenged guinea pigs. There were no irritant skin reactions in control groups. Based on results, 2-Mercaptobenzothiazole is graded as a moderate sensitizer according to Magnusson and Kligman.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30 %
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30 %
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30 %
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
erythema (score 1) in 3 female animals
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30 %
No. with + reactions:
8
Total no. in group:
20
Clinical observations:
erythema (score1 ) in 3 males and 5 females, edema (score 1) in 1 male and1 female

After, removal of the occlusive dressing on day 10 after epidermal induction, irritation at the application site was seen in 19 of 20 guinea pigs of the test groups.

Body weights were not affected by the treatment.

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The test article was graded as a moderate sensitiser according to the Magnusson and Kligman maximisation scale.
Executive summary:

A guinea pig maximisation test was initiated to determine sensitising properties of the test material after challenge exposure by skin contact. The procedure of Magnusson and Kligman for adjuvant tests was followed. Epidermal challenge of 10 male and 10 female guinea pigs (test groups) resulted in positive responses in 3 female guinea pigs after 24 hours and in 3 male and 5 female guinea pigs after 48 hours, corresponding to a sensitisation rate of 40%. No irritant skin reactions were recorded for control animals. Body weights at start and on conclusion of the test were unaffected by the treatment. The test article was graded as a moderate sensitiser according to the Magnusson and Kligman maximisation scale.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In a GLP-compliant guinea pig maximization test following OECD guideline No. 406 the test article's potential to cause skin hypersensitivity was assessed in 30 albino guinea pigs (10 control group, 20 test group). Test substance concentrations were based on the results of a preliminary study. In the main study, 20 experimental animals were intradermally injected with a 5% concentration (in peanut oil) and epidermally exposed to a 50% concentration (in vaseline). Three pairs of injections were given (adjuvant/saline; test item in vehicle; test item in vehicle plus adjuvant/saline). The control animals were similarly treated, but with vehicle replacing the test article. Two weeks after the epidermal application all animals were challenged with a 30% test substance concentration (in vaseline) and the vehicle for 24 hours. Positive responses were recorded in 3 female guinea pigs after 24 hours and in 3 male and 5 female guinea pigs after 48 hours, corresponding to a sensitisation rate of 40%. No irritant skin reactions were recorded for control animals.

A Bühler study yielded ambiguous results with skin reactions in both the test and control group animals, probably related to irritation properties of the test article.

Overall, the test article is considered to be a mild sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No 1272/2008. Based on the data available the test article is a sensitizer of category 1B and classification with H317 is warranted under Regulation (EC) No 1272/2008,as amended for the eighth time in Regulation (EU) No 2016/218.