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Description of key information

The key study for skin sensitisation is read across from the structurally analogous substance octamethyltrisiloxane (CAS 107-51-7). The test material was found not sensitising in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (RCC 1999).

The selected study is the only skin sensitisation study available for a relevant surrogate substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

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:
01 Dec 1998 - 15 Feb 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.
Species:
guinea pig
Strain:
other: Ibm: GOHI; SPF- quality guinea pigs
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Fullinsdorf, Switzerland
- Age at study initiation: 5-7 weeks
- Weight at beginning of acclimation period: 304-380 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: One week for the control and test group under test conditions after health examination. No acclimation of animals of the pretest. Only animals without any visible signs of illness were used.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
olive oil
Concentration / amount:
Induction 100%, challenge 50%, positive control: intradermal induction 5% , epidermal induction 50% , challenge 50% (vehicle mineral oil)
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
Induction 100%, challenge 50%, positive control: intradermal induction 5% , epidermal induction 50% , challenge 50% (vehicle mineral oil)
No. of animals per dose:
Control group: 5
Test group: 10
Intradermal pretest: 1
Epidermal pretest: 2
Positive control: 10 test, 5 control
Details on study design:
PRE TEST: This was carried out to identify a suitable concentration of the test article for the induction phase of the main study and a non-irritant concentration for the challenge phase. The concentrations tested were for the epidermal application the most qualified to assure an optimum technical application procedure and for the intradermal injection the selected concentrations were tested at 1, 3 and 5%.

MAIN STUDY:

INTRADERMAL INJECTIONS (DAY 1)

Three pairs of intradermal injections (0.1 ml/sire) were made at the border of a 4x6 cm area in the clipped region as follows:

TEST GROUP:
1. 1:1 (v/v) mixture of FCA and physiological saline.
2. The test article, at 5% in olive oil.
3. The test article at 5% in a 1:1 (v/v) mixture of FCA and physiological saline
CONTROL GROUP:
1. 1:1 (v/v) mixture of FCA and physiological saline.
2. Olive oil.
3. 1:1 (w/w) mixture of oilive oil in a 1:1 (v/v) mixture of FCA and physiological saline.


EPIDERMAL APPLICATIONS (DAY 8)

TEST GROUP:
One week after the injections the scapular area was shaved free of hair again prior to the epidermal application. Filter paper was saturated with the undiluted test material and placed over the injection sites of the test animals. The volume of the test article was ca. 0.3 ml. The patch was covered withaluminium foil and firmly secured by an elastic plaster wrapped around the trunk of the animal and secured with impervious adhesive tape. The dressings were left in place for 48 hours. The epidermal application procedure described ensured intensive contact of the test article. The reaction sites were assessed for erythema and oedema 24 and 48 hours after removal of the dressing, using the numerical grading system according to Draize.

CONTROL GROUP:
The guinea pigs of the control group were treated as described above with olive oil only, also applied at a volume of ca. 0.3 ml.


CHALLENGE TEST (DAY 22)

The test and control animals were challenged two weeks after the epidermal induction application. The test and control guinea pigs were treated in the same way.
Hair was clipped and shaved from a 5x5 cm area on the left and right flank of each guinea pig just prior to application. Two patches of filter paper were saturated with the test article at the highest non-irritating concentration of 50% (left flank) and the vehicle only (olive oil applied to the right flank) using the same method as for the epidermal application. The volume of test article or vehicle applied was approximately 0.2 ml. The dressings were left in place for 24 hours.
After ca. 21 hours after removal of the dressing the test sites treated with the test article were depilated as described in the epidermal pretest. Approximately 24 and 48 hours after the removal of the dressing the application sites were assessed for erythema and oedema using the numerical scoring system according to Draize.
Challenge controls:
Challenge controls were treated in the same way as the test group.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was found not sensitising in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In the key study for sensitisation with read-across substance octamethyltrisiloxane (CAS 107-51-7) male and female guinea pigs were tested for skin sensitisation in a guinea-pig maximisation test (RCC, 1999). There were no positive reactions to treatments in any of the test animals. Appropriate positive and negative controls were in place.

Read-across justification

Decamethyltetrasiloxane (L4) belongs to the structural class of siloxanes (alkyl, vinyl, aryl or hydrogen substituted). The substances all have high log Kow (increasing with increasing chain length) and low water solubility. In vivo skin sensitisation data are available for a number of these substances, none of which shows any evidence of sensitisation.

Summary of key sensitisation data for linear siloxanes

Substance

L2

L3

L4

L5

Chemical name

Hexamethyl

disiloxane

Octamethyl

trisiloxane

Decamethyl

tetrasiloxane

Dodecamethyl

pentasiloxane

CAS number

107-46-0

107-51-7

141-62-8

141-63-9

Skin sensitising result

Not sensitising (Dow Corning Corporation, 1992)

Not sensitising (RCC, 1999)

-

-

 

In addition to the data shown in the table, there is also no evidence of any skin sensitising potential for the corresponding cyclic siloxanes.

In light of the available data and the absence of any structural features indicative of skin sensitising potential, it is therefore valid to read-across a result of “not sensitising” where there are data gaps.





Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available information L4 does not require classification for skin sensitisation according to Regulation (EC) No 1272/2008.