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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation

The test substance shows no skin sensitising potential in the Guinea Pig Maximization test.

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 May 20, 2009 to November 5, 2009
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:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
2003
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
other: MAFF in Japan, 12-Nousan-No. 8147, 2-1-6
Version / remarks:
2000
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
GPMT test conducted in 2009 prior to worldwide acceptance of the LLNA.
Specific details on test material used for the study:
Lot/Batch no.: 08072
Description: Pale yellow green powder
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Oh-hara production facility (Shizuoka, Japan) of Japan SLC, Inc.
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: ca. 7 weeks at dosing
- Weight at study initiation: 371 – 479g
- Housing: Groups of 5 animals housed in cages (485 mm in width x 570 mm in depth x 360 mm in height)
- Diet: Certified pellet diet LRC4 (Lot No. 090305; Oriental Yeast Co., Ltd., Tokyo, Japan)
- Water: Tap water, ad libitum
- Acclimation period: 11 days before application

ENVIRONMENTAL CONDITIONS
- Temperature: 21.8 – 22.4°C
- Humidity: 21.8 – 22.4°C
- Air changes (per hr): 10 or more
- Photoperiod: Alternating 12-hour artificial light and dark cycles. light on at 7:00 a.m. and off at 7:00 p.m.).
- IN-LIFE DATES: From 02-Jun-2009 to 26-Jun-2009
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Remarks:
or a 1:1 w/w mixture of Freunds’ Complete Adjuvant with water
Concentration / amount:
1% (intradermal) and 50% (epicutaneous occlusive)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Remarks:
or a 1:1 w/w mixture of Freunds’ Complete Adjuvant with water
Concentration / amount:
50%
Adequacy of challenge:
other: Maximum practical concentration that could be prepared and dosed topically and did not give rise to irritating effects.
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS: Yes
Intradermal injections: In 2 guinea pigs, 0.5 and 1%, w/v. test substance was injected; skin responses were assessed approximately 24 hour later
Topical applications: 4 guinea pigs (2 concentrations / animal), 5, 10, 25 and 50%, w/w; reaction sites were assessed for erythema and edema at 24 hours after removal of the patch

Result of range finding tests:
Intradermal injections: Diffuse or patchy erythema (score 1) and/or moderate dispersed erythema (score 2) were observed on the 0.5% and 1% injected skin sites of 2 animals.
Topical applications: No visible change (score 0) were found on the 5 and 50% of the test substance applied skin sites of 2 animals, and on the 10 and 25% of the test substance applied skin sites of 2 animals.

MAIN STUDY

The following 4 groups were set:
Group/ Induction Exposure / Challenge Exposure
A/ Test item/ Test item
B/ None/ Test item
C/ HCA/ HCA
D/ None/ HCA
HCA: α-Hexylcinnamaldehyde (positive control)

A. INDUCTION EXPOSURE

A.1. Intradermal induction (first induction)
- Test group: 1 (A) (20 animals)
- Control groups: 3 (B, C, D) (10/ 10/ 5 animals)
- Site: Shoulder region of each animal was clipped using an electric clipper
- Frequency of applications: 3 pairs of intradermal injections (0.1 mL each)
- Duration: 7 days
- Concentrations: 1%
[1] Emulsion of FCA (Freund’s complete adjuvant) and SPS (sterilized physiological salt solution) at the rate of 1:1 (v/v)
[2] Suspension of the test substance or solution of HCA in liquid paraffin
[3] Emulsion of the test substance in FCA blended with SPS at the rate of 1:1 (v/v) or emulsion of HCA in FCA blended with SPS at the rate of 1:1 (v/v)
The animals in Group B and D were given similar injections without the supplementation of the test substance and HCA.

A.2. Topical induction (Reinduction)
- Exposure period: On Day 7 after the intradermal induction
Pretreated with 0.5 mL of 10% sodium lauryl sulfate (Kanto Chemical Co., Inc.) in white petrolatum by rubbing on Day 6 after the intradermal induction (after clipping on the day before the topical induction).
- Test group: 1 (A) (20 animals)
- Control groups: 3 (B, C, D) (10/ 10/ 5 animals)
- Site: On the day before application, the shoulder region of each animal was clipped again.
- Frequency of applications: Once
- Duration: 48 hours
- Concentrations: 50%
Group A, 0.4 g of the test substance formulation
Group C, 0.4 mL of the HCA formulation
Animals in the Group B and D were treated with the corresponding vehicle used for preparation of the test substance and HCA formulation.

B. CHALLENGE EXPOSURE
- Day(s) of challenge: On Day 14 after the topical induction
- Exposure period: 24 hours
- Test group: 1 (A) (20 animals)
- Control groups: 3 (B, C, D) (10/ 10/ 5 animals)
- Site: 2 cm x 2 cm of the left flank for each animal. In addition, the white petrolatum for Groups A and B or liquid paraffin for Groups C and D was treated on the right flank of each animal.
- Concentrations: 0.2 g of the test substance formulation (50%) in white petrolatum for Groups A and B or 0.2 mL of HCA formulation (10 %) in liquid paraffin for Groups C and D was applied
- Evaluation (hr after challenge): At 24 and 48 hours after the challenge patch removal

Challenge controls:
The positive control with alpha-hexylcinnamaldehyde techn. 97.8% showed that the test system was able to detect sensitizing compounds under the laboratory conditions chosen.
Positive control substance(s):
yes
Remarks:
HCA: α-Hexylcinnamaldehyde (positive control)
Positive control results:
Group C:
In the HCA-treated group, 8 of 10 animals exhibited the reaction of score 2 (moderate dispersed erythema), 1 animal exhibited the reaction of score 1 and the remaining 1 animal exhibited the reaction of score 0.

Group D:
On the other hand, all 5 animals in the unsensitized / HCA-challenged group exhibited score 0.
Therefore, the sensitization rate of HCA-treated group was calculated to be 90% (9/10) and the skin sensitization was evaluated to be Classification V (extreme). This was considered to sufficiently assure the reliability of this study.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10%
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
7 animals with score 1 (diffuse or patchy erythema), 1 animal with score 2 (moderate dispersed erythema)
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
8 of 10 animals exhibited the reaction of score 2 (moderate dispersed erythema), 1 animal exhibited the reaction of score 1 (diffuse or patchy erythema) and the remaining 1 animal exhibited the reaction of score 0.
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Key study: Skin sensitisation_ 2009/1130545

The test substance was assessed for its skin sensitizing potential using the maximization assay in guinea pigs. Doses were based upon a preliminary irritation test and resulted in a 1% concentration for intradermal induction, and a 50% concentration for both topical induction and challenge.

At challenge, no skin reaction was noted in treated guinea pigs.

Based on this study, the test substance shows no skin sensitizing potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. In the challenge no skin sensitising effects were observed for the test substance. As a result the substance is not considered to be classified for skin sensitisation under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/918.