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Description of key information

In a study according OECD TG 406 performed on guinea-pigs the substance is not to be classified as skin sensitizer (reference 7.4.1 -1).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jan 29 - Sep 24, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1996
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
With the existing data from this study not only being acceptable but of good quality (Klimisch Score 1), this study precludes the need for an additional LLNA study. In addition, a supplementary LLNA study would violate the ECHA objectives with regards to animal welfare.
Species:
guinea pig
Strain:
other: HsdPoc:DH
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen
- Age at study initiation: about 6 weeks
- Weight at study initiation: The mean initial body weight at the start of the study was 363 g (range from 337 to 391 g).
- Housing: Five guinea pigs were housed in type GM/5 (EBECO) Makrolon cages with a shelter and placed on mobile racks.
- Diet: ad libitum, Provimi Kliba 3418.0
- Water: ad libitum, tap water
- Acclimation period: 7 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 23
- Humidity (%): 55 to 60
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
paraffin oil
Concentration / amount:
50g/L/0.1 mL
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
50 g/L
Day(s)/duration:
Day 8/48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
10 g/L
Day(s)/duration:
Day 22/24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Pretest: 5 females
Group 1: negative control group (5 females)
Group 2: test material group (10 females)
Details on study design:
RANGE FINDING TESTS:
- no pretreatment, intradermal injection: 0, 1, 5, 10, 25, 50 g/L given to one animal in paraffin oil
- topical applications (48 h), no pretreatment: 1, 10, 50, 100, and 200 g/L in polyethylene glycol 400
- topical applications (24 h), FCA pretreatment: 1, 5, 10, and 50 g/L in polyethylene glycol 400

MAIN STUDY
A1. INDUCTION EXPOSURE (intradermal injection)
- No. of exposures: 6 injections of 0.1 mL each, three on each side of the spinal column
- Test groups: 0.1 mL FCA + NaCl, 0.1 mL 50g/L test item ad liquid paraffin, 0.1 mL FCA + 50 g/L test item in NaCl solution
- Control group: 0.1 mL FCA + NaCl, 0.1 mL liquid paraffin, 0.1 mL FCA + NaCl- Site: cranial, medial, caudal
- Frequency of applications: single

A2. INDUCTION EXPOSURE (topical application)
- No. of exposures: one week after injection (A1) single topical application of a filter plate soaked with either test solution, or vehicle
- Test groups: 50 g/L test material ad PEG 400
- Control group: PEG 400
- Site: cranial, medial, caudal- Frequency of applications: single
- Duration: 48 h, occlusive

B. CHALLENGE EXPOSURE
- No. of exposures: single two weeks after topical induction (A2)
- Day(s) of challenge: 1d
- Exposure period: 2 weeks after topical application
- Test groups: 10 g/L test item ad PEG 400- Control group: PEG 400
- Site: cranial, medial, caudal
- Evaluation (hr after challenge): 48 and 72 h
- Observations
During the induction phase, the guinea pigs were examined on days 2, 3, 7, 11, 12, 15, and 22 of the experimental part for local skin reactions and the results were documented.The behavior and general condition of all animals were monitored daily. The challenge sites were investigated for reactions 48 hours after start of the challenge. Further inspections followed 72 hours after start of the challenge, to detect weak or slowly developing reactions. After the challenge, skin changes at the application sites were evaluated according to the following MAGNUSSON and KLIGMAN scheme.
Positive control substance(s):
yes
Remarks:
Hexylcinnamaldehyde
Positive control results:
50% positive reactions with control substance
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10 g/L
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of toxicity
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
10 g/L
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of toxicity
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 g/L
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0 g/L
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
10 g/L
No. with + reactions:
5
Total no. in group:
10
Interpretation of results:
GHS criteria not met
Conclusions:
Under the given experimental conditions, the test material induced no skin sensitization.
Executive summary:

The test material was investigated for skin sensitizing properties in the guinea pig maximization test according to MAGNUSSON and KLIGMAN (1969). 5 females were treated with the vehicles liquid paraffin and polyethylene glycol 400 (group 1) and 10 females were treated with the test material (group 2). Induction included intradermal injection of the test material preparation in liquid paraffin (50 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application of test material preparation in polyethylene glycol 400 (50 g/L) for 48 hours on experimental day 8.

Challenge by topical application of the test material preparation in polyethylene glycol 400 (10 g/L) for 24 hours was performed two weeks after topical induction and readings were taken at 48 hours and 72 hours after start of treatment.

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. After challange no positive reactions were seen 48 or 72 hours after treatment with the test material.

Under the given experimental conditions, the test material induced no skin sensitising reactions.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The test material was investigated according to OECD TG 406 for skin sensitizing properties in the guinea pig maximization test according to MAGNUSSON and KLIGMAN (1969). 5 females were treated with the vehicles liquid paraffin and polyethylene glycol 400 (group 1) and 10 females were treated with the test material (group 2). Induction included intradermal injection of the test material preparation in liquid paraffin (50 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application of test material preparation in polyethylene glycol 400 (50 g/L) for 48 hours on experimental day 8.

Challenge by topical application of the test material preparation in polyethylene glycol 400 (10 g/L) for 24 hours was performed two weeks after topical induction and readings were taken at 48 hours and 72 hours after start of treatment.

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. After challange no positive reactions were seen 48 or 72 hours after treatment with the test material.

Under the given experimental conditions, the test material induced no skin sensitizing reactions.

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 test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this information, the substance is not considered to be classified for skin sensitisation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.