Registration Dossier

Administrative data

Description of key information

The test substance is not a skin sensitizer.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no positive control animals to demonstrate the sensitivity and reliability of the test.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA skin sensitisation study does not need to be conducted because adequate data from an in vivo GPMT skin sensitisation study is available.
Test material information:
Composition 1
Specific details on test material used for the study:
Appearance: liquid
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Environmental Safety Division Unilever
- Weight at Start: males: 320-342 g; females: 336-368 g
Route:
intradermal
Vehicle:
other: Dobs/saline
Concentration / amount:
1%
Day(s)/duration:
Single
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
10%
Day(s)/duration:
The patch is held in place for 48 hours. Fourteen days thereafter the animals were challenged.
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
1%
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Test animals: 10 (6 males, 4 females)
Control animals: 8 (4 males, 4 females)
Details on study design:
RANGE FINDING TESTS
- Intradermal injections: Intradermal injections (0.1 mL/site) were made into the clipped flank of four males at concentrations of 0.1, 0.25, 0.5 and 1% of the test substance in 0.01% Dobs/saline. Twenty-four hours later the reactions were examined for size in millimetres (lenght and breadth), erythema and oedema.
- Epidermal application: Eight millimetre diameter filter paper patches in 11 mm aluminium patch test cups were saturated with concentrations of 5, 10 and 25% in ethanol and the cups were applied to the shaved flanks of four males and weighing approximately 450 g. The patches were held in place by adhesive plaster wound around the trunk. The patches were removed 24 hours after application and the treatment sites examined 24 and 48 hours after removal of the patches. The resulting reactions were scored for irritation on a scale from 0 to +++. For shoulder induction, a concentration giving slight but definite irritation was selected. The highest concentration which causes no visible irritation was selected for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
1) Intradermal injections
- Concentration: 1%
- Site: the dorsal scapular region
Three pairs of intradermal injections (0.1 mL/site):
1) Freund's complete adjuvant (FCA) 50:50 with 0.01% Dobs/saline
2) Test substance at 1% in 0.01% Dobs/saline
3) Test substance at 2% in 0.01% Dobs/saline in a 50:50 mixture of FCA with 0.01% Dobs/saline

2) Topical applications one week after the injections:
- Concentration: 10% (in ethanol)
- Amount: saturated patch (control animals: ethanol only)
- Area: 8 cm^2
- Exposure period: 48 hours (occlusive)
- Readings: 24 and 48 hours after patch removal

Controls:
Treated controls: At the same time as the test animals were selected, 4 males were selected as treated controls for the first challenge. They were given a mock induction treatment at the same time and in the same way as for the test animals except that test substance was omitted from the injection and application preparations. At first challenge they were treated in exactly the same way as the test substance.
Untretaed controls: At every challenge in the test 4 previously untreated female or male animals and weighing approximately the same as the test animals at that challenge were treated in exactly the same way as the test animals. When animals of similar weight to the test animals were not available, those as close as possible in weight were selected from stock.

B. CHALLENGE EXPOSURE (control and test group)
- Day of challenge: Fourteen days after application of the induction patch. One week after the first challenge a second challenge was made on the opposite flank exactly as for the first challenge. Two additional challenges were performed.
- Concentrations: 1%
- Exposure period: 24 hours (occlusive)
- Sites: clipped and shaved flank
- Amount: saturated patch
- Readings: 24 and 48 hours after patch removal

A reaction was considered to be a sensitization reponse if: response produced scattered, mild erythema (faint pink) or greater and there were no reactions in controls or no reaction greater than barely perceptible erythema in controls.
Positive control substance(s):
no
Key result
Reading:
other: 1st, 2nd, 3rd and 4th reading
Hours after challenge:
24
Group:
other: untreated controls
Dose level:
1%
No. with + reactions:
0
Total no. in group:
4
Key result
Reading:
other: 1st, 2nd, 3rd and 4th reading
Hours after challenge:
48
Group:
other: untreated controls
Dose level:
1%
No. with + reactions:
0
Total no. in group:
4
Key result
Reading:
other: 1st, 2nd, and 4th reading
Hours after challenge:
24
Group:
other: treated controls
Dose level:
1%
No. with + reactions:
0
Total no. in group:
4
Key result
Reading:
other: 3rd reading
Hours after challenge:
24
Group:
other: treated controls
Dose level:
1%
No. with + reactions:
1
Total no. in group:
4
Key result
Reading:
other: 1st, 2nd, 3rd and 4th reading
Hours after challenge:
48
Group:
other: treated controls
Dose level:
1%
No. with + reactions:
0
Total no. in group:
4
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10
Key result
Reading:
other: 2nd and 4th reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
other: 2nd and 4th reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
other: 3rd reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10
Key result
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10

Irritation in the preliminary study

- As faint pink to pale pink erythema and oedema was observed with 1% in the four animals, this concentration was selected as the intradermal induction concentration.

- At the topical induction of 10% test substance all 4 animals showed barely perceptible erythema 24 hours after treatment. 48 hours after treatment 2 animals showed scattered, mild erythema (faint pink), 1 animal showed barely perceptible erythema and 1 animal showed no effects. For the challenge 1% was determined to be the highest non-irritant concentration.

Interpretation of results:
GHS criteria not met
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached justification
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
Key result
Reading:
other: 1st, 2nd, 3rd and 4th reading
Hours after challenge:
24
Group:
other: untreated controls
Dose level:
1%
No. with + reactions:
0
Total no. in group:
4
Key result
Reading:
other: 1st, 2nd, 3rd and 4th reading
Hours after challenge:
48
Group:
other: untreated controls
Dose level:
1%
No. with + reactions:
0
Total no. in group:
4
Key result
Reading:
other: 1st, 2nd, and 4th reading
Hours after challenge:
24
Group:
other: treated controls
Dose level:
1%
No. with + reactions:
0
Total no. in group:
4
Key result
Reading:
other: 3rd reading
Hours after challenge:
24
Group:
other: treated controls
Dose level:
1%
No. with + reactions:
1
Total no. in group:
4
Key result
Reading:
other: 1st, 2nd, 3rd and 4th reading
Hours after challenge:
48
Group:
other: treated controls
Dose level:
1%
No. with + reactions:
0
Total no. in group:
4
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10
Key result
Reading:
other: 2nd and 4th reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
other: 2nd and 4th reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
other: 3rd reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10
Key result
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Animal

For the determination of the skin sensitising properties of the substance to be registered, data on a structural analogue: 2 -heptylcyclopentanone was used. The justification for the use of data on 2 -heptylcyclopentanone is included in the dossier. 2 -Heptylcyclopentanone was tested by performing a guinea pig maximisation test equivalent to the OECD 406 guideline. No reliable positive controls were included. A concentration of 1% was used for the intradermal induction, 10% for the epidermal induction and 1% for the challenge. Four challenges were performed and the skin was scored 24 and 48 hours after removal of the patches. No positive effect was observed in the treated and untreated controls except for one treated control animal in challenge 3, 24 hours after patch removal. Forty-eight hours after patch removal in challenge 1 and 3, in one animal, a positive effect (scattered, mild erythema) was observed. In challenge 3, in another animal, a positive effect (scattered, mild erythema) was observed 24 hours after patch removal. Based on the faint reactions in this study, the substance is not considered a sensitizer.

Human

Thirty-five volunteers (29 volunteers completed the study) were exposed to 4% test substance in petrolatum. The test substance is applied under occlusive dressing to the same sites on the volar forearms for five 48-hour periods. Prior to the first exposure, the site was pre-treated with 2% aqueous SLS under occlusion for 24 hours. Following a 10 to 14-day rest period, a challenge patch of the test substance is applied to a different site for 48 hours under occlusion. Half of the challenge sites is pre-treated for 0.5 hour with 2% aqueous SLS under occlusion. Observations are made immediately after removal of the challenge patch and 24 hours thereafter. No effects were observed.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The test substance does not have to be classified for skin sensitisation according to Regulation (EC) No 1272/2008.