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Description of key information

Not skin sensitising

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:
From February 28 to April 13, 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: Mangusson, B., Kligman, A.M., 1970. " Allergenic Contact Dermatitis in the Guinea-Pig: Identification of Contact Allergens"
Deviations:
not specified
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A LLNA study has not been conducted because adequate data from guinea pig Maximisation test study are already available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 230 - 343 g (♂); 263 - 317 g (♀)
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 342, Batch 50/89 guinea pig breeding/ maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum
- Acclimation period: Six days under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3 °C
- Humidity (%):40-70 %
- Air changes (per hr): 10-15 air changes per hour and hourly monitored environment
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light/12 hours dark.
- Music/light period
Route:
other: Pretest intradermal injection
Vehicle:
water
Concentration / amount:
5%, 3%, 1%
Route:
other: Pretest epidermal application
Vehicle:
petrolatum
Concentration / amount:
25%, 10%, 5%, 3%
No.:
#1
Route:
intradermal
Vehicle:
petrolatum
Concentration / amount:
3%
No.:
#2
Route:
other: epidermal application
Vehicle:
petrolatum
Concentration / amount:
5 %
No. of animals per dose:
Pretest
Intradermal injection: 1 animals per sex, 3 concentrations per animal
Epidermal application: 2 animals per sex, 4 concentrations per animal
Main study
10 animals per sex per concentration
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three pair of intradermal injection
- Exposure period:
injection: 1 week before epidermal treatment,
epidermal exposure: 48 hours
- Test groups: 10 males and 10 females guinea pig
- Control group: 5 males and 5 females guinea pig treated as the test group with the omission of the test article
- Site: area of dorsal skin from the scapular region (ca. 6*8 cm) clipped free of hair
- Concentrations of intradermal injection :
1) Freunds' complete adjuvant 50:50 with distilled water for injection;
2) the test article, diluited to 3% with distilled water;
3) the test article at concentration used in 2), emulsified in a 50:50 mixture of Freunds' complete adjuvant and the vehicle used in 2)
- Concentrations of epidermal application: 10% in petrolatum oil

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after the epidermal induction application
- Exposure period: 24 hours after the application, the patches were removed
- Test groups: 10 males and 10 females guinea pig
- Control group: 5 males and 5 females guinea pig treated as the test group (with 5% of the test substance)
- Site: clipped and shaved area of 5*5 cm in the left and right flank of each guinea pig
- Concentrations: 5% in petrolatum oil on the right flank of guinea pigs; only vehicle on the left flank of guinea pigs
- Evaluation (hr after challenge): immediately, 24 hours and 48 hours after removal of patches

OTHER:

RE-CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after the first challenge
- Exposure period: 24 hours after the application, the patches were removed
- Test groups:10 males and 10 females guinea pig
- Control group:5 males and 5 females guinea pig treated as the test group with the vehicle only
- Site: clipped and shaved area of 5*5 cm in the left and right flank of each guinea pig
- Concentrations:
Test group: 5% in petrolatum oil on the right flank of guinea pigs; only vehicle on the left flank of guinea pigs
Control group: vehicle only on the left flank
- Evaluation (hr after challenge): immediately, 24hours and 48 hours after removal of patches

Test condtions

Pretest intradermal injection: Distilled water;
Pretest epidermal application: Petrolatum oil;
Main test: Petrolatum oil

Pretest (intradermal injection)
5%, 3%, 1%
Pretest (epidermal application)
25%, 10%, 5%, 3%

Main test (intradermal injection)
According to the Mangusson-Kligman, and to the findings observed, the concentration selected for the main study was 3%
Main test (epidermal application)
According to the Mangusson-Kligman, and to the findings observed, the concentration selected for the induction period was 10% and for the challenge procedure 5%.

Positive control substance(s):
yes
Remarks:
A control group is tested with Dinitro-chloro-benzene twice a year as a sensitivity check of the guinea pig strain
Positive control results:
positive control with DNCB
positive reaction/total animals: 67%
Reading:
1st reading
Hours after challenge:
24
Group:
other: Control Group
Dose level:
5% in petrolatum oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Control Group. Dose level: 5% in petrolatum oil. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: Control Group
Dose level:
only vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Control Group. Dose level: only vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Control Group
Dose level:
5% in petrolatum oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Control Group. Dose level: 5% in petrolatum oil. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Control Group
Dose level:
only vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Control Group. Dose level: only vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5% in petrolatum oil
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% in petrolatum oil. No with. + reactions: 3.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
only vehicle
No. with + reactions:
0
Total no. in group:
2
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: only vehicle. No with. + reactions: 0.0. Total no. in groups: 2.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% in petrolatum oil
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% in petrolatum oil. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
only vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: only vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
only vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: only vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
only vehicle
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: only vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
5% in petrolatum oil
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 5% in petrolatum oil. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
5% in petrolatum oil
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 5% in petrolatum oil. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
only vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: only vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
only vehicle
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: only vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Interpretation of results:
other: CLP criteria not met
Conclusions:
Not sensitising
Executive summary:

The substance was tested according to OECD 406, EU Method B.6 and according to Mangusson, B., Kligman, A.M., 1970. " Allergenic Contact Dermatitis in the Guinea-Pig: Identification of Contact Allergens". During the test 5 males and 5 females guinea pigs were used as control group, treated with vehicle only during the Induction test and 10 males and 10 females were used as test group, treated with test article during the all parts of the experiment.

The test shows low reactions to the test item, up to 15% of positive reaction.

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

The only study available, conducted according to internationally accepted guidelines and GLP, shows low sensitising effects on the guinea-pig. The highest positive reaction value of the test is 15% responding at 3% intradermal induction dose.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to the CLP Regulation EC n. 1272/2008 a skin sensitiser is a substance that will lead to an allergic response following skin contact. Substances shall be classified as skin sensitisers (Category 1) where data are not sufficient for sub- categorisation in accordance with the following criteria:

(a) if there is evidence in humans that the substance can lead to sensitisation by skin contact in a substantial number of persons; or

(b) if there are positive results from an appropriate animal test.

The specific criteria for the Guinea pig maximisation test are for the sub categorisation 1A:

- ≥ 30 % responding at ≤ 0,1 % intradermal induction dose or

- ≥ 60 % responding at > 0,1 % to ≤ 1 % intradermal induction dose;

For the sub categorisation 1B the specific criteria are:

- ≥ 30 % to < 60 % responding at > 0,1 % to ≤ 1 % intradermal induction dose or

- ≥ 30 % responding at > 1 % intradermal induction dose

Therefore the tested substance has not to be classified as skin sensitiser because the highest positive reaction value of the test is 15% responding at 3% intradermal induction dose.

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