Registration Dossier

Administrative data

Description of key information

All available key data for linear siloxanes have been included to the dataset for the registered substance, L5 (dodecamethylsiloxane, CAS 141-63-9) as weight of evidence to assess the skin sensitisation endpoint.

HMDS: The skin sensitisation study with HMDS (hexamethyldisiloxane, CAS 107-46-0) is a guinea pig maximisation study, conducted using a study protocol comparable with OECD Test Guideline 406 and in compliance with GLP (Dow Corning Corporation, 1992), HMDS was not sensitising to the skin.

L3: In the skin sensitisation study with (octamethyltrisiloxane, CAS 107-51-7), conducted according to OECD Test Guideline 406 and in compliance with GLP, the test material was concluded to be not sensitising to skin (RCC, 1999).

L4: There are no skin sensitisation data with L4 (decamethyltetrasiloxane, CAS 141-62-8).

L5: There are no skin sensitisation data with L5 (dodecamethylsiloxane, CAS 141-63-9).

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:
weight of evidence
Study period:
10/09/1991 to 13/01/1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
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:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory
- Age at study initiation: No data
- Weight at study initiation: 338-387 g
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: 09/10/1991 To: 02/11/1991
Route:
intradermal and epicutaneous
Vehicle:
other: ethanol and saline (unchanged (at challange))
Concentration / amount:
Various concentrations used in the induction phase, and HMDS was undiluted in the challenge phase.
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol and saline (unchanged (at challange))
Concentration / amount:
Various concentrations used in the induction phase, and HMDS was undiluted in the challenge phase.
No. of animals per dose:
15; 10 males in the test group and 5 males in the negative control group. 
Details on study design:
Preliminary test:

The hair of both flanks was clipped prior to dosing. Various concentrations (25, 50, 75 and 100%) of L2 were applied to the cotton pads of Hilltop Chambers and then applied to the flank skin. The sites were then wrapped with adhesive tape and unwrapped after approximately 24 hours and evaluated for erythema and oedema.

Main study:

For the first stage of induction, an area over the shoulder region was clipped on each animal. Three pairs of intradermal injections (0.1 ml each) were made simultaneously on previously identified sites (A, B and C), so that there was a row of three injections on each side of the spine. The injection sites were just within the boundaries of a 2x4 cm patch which was applied one week later. Injections were administered as follows:

Test substance:
A: 0.1 ml of a 50% suspension of FCA in saline.
B: 0.1 ml of 5% HMDS in 80% ethanol (suspension).
C: 0.1 ml of 10% HMDS in 80% ethanol + 50% FCA in saline (suspension).

Negative controls:
A: 0.1 ml of 50% suspension of FCA in saline.
B: 0.1 ml of 80% ethanol (solution).
C: 0.1 ml of 80% ethanol + 50% FCA in saline (suspension).

On day 7 the area of injections was clipped in preparation for the second induction. Patches of filter paper were saturated with the following solutions: a) test group - undiluted L2 and b) negative controls - 80% ethanol. The patches were positioned on the intradermal injection sites and secured in place with an occlusive bandage for 48 hours and then unwrapped.

The challenge phase began two weeks following topical induction. The animals were prepared by clipping a 5x5 cm area on both flanks. For dosing, 0.3 ml of the test (100%) or control ethanol solutions were applied to a Hilltop Chamber (occlusive) and the chamber applied to the flank area and wrapped with gauze dressing and adhesive tape for 24 hours.

The wrappings were removed 24 hours later and the readings were made at 24 and 48 hours after patch removal and scored for erythema and oedema. Body weights were taken at the beginning of the study and at 7, 14 and 21 days. Erythema or oedema at least two grades higher than that seen in the negative control group was considered evidence of an allergic response.
Challenge controls:
Ethanol solution
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No evidence of skin irritation or sensitization following challenge phase. Intradermal injection sites showed necrosis and scabbing typical of Freund's Complete Adjuvant response. No obvious effects on body weight gain or food consumption.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Ethanol
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:
Ethanol
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Group:
positive control
Remarks on result:
other: not included in the study.
Interpretation of results:
GHS criteria not met
Conclusions:
In a guinea pig maximisation study conducted using a study protocol comparable with OECD 406 and to GLP (reliability score 1) L2 was not sensitising to the skin.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
01 Dec 1998 - 15 Feb 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
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 pre-test. 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 pre-test: 1
Epidermal pre-test: 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 olive 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 with aluminium 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 pre-test. 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
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
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
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
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
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
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:

All available key data for linear siloxanes have been included to the dataset for the registered substance, L5 (dodecamethylsiloxane, CAS 141-63-9) as weight of evidence to assess the skin sensitisation endpoint.

HMDS: The skin sensitisation study with HMDS (hexamethyldisiloxane, CAS 107-46-0) is a guinea pig maximisation study, conducted using a study protocol comparable with OECD Test Guideline 406 and in compliance with GLP (Dow Corning Corporation, 1992), guinea pigs were initially exposed to 25, 50, 75 or 100% HMDS (ethanol vehicle) to determine the irritating potential of HMDS. Since no irritation was observed in the preliminary test, undiluted HMDS was used in the main test. There was no evidence of skin irritation or skin sensitisation following the challenge phase. Intradermal injection sites showed necrosis and scabbing typical of Freund's Complete Complete Adjuvant response. There were no significant effects on body weight gain or food consumption.

L3: In the skin sensitisation study with (octamethyltrisiloxane, CAS 107-51-7), conducted according to OECD Test Guideline 406 and in compliance with GLP, the test material was concluded to be not sensitising to skin (RCC, 1999). Following challenge with 50% test material in corn oil, no indication of skin sensitisation was observed in any of the 10 test animals.

L4: There are no skin sensitisation data with L4 (decamethyltetrasiloxane, CAS 141-62-8).

L5: There are no skin sensitisation data with L5 (dodecamethylsiloxane, CAS 141-63-9).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available information read across from the structurally analogous substances hexamethyldisiloxane (HMDS; CAS 107-46-0), octamethyltrisiloxane (L3; CAS 107-51-7) and decamethyltetrasiloxane (L4; CAS 141-62-8), no classification is proposed for dodecamethylpentasiloxane in accordance with Regulation (EC) No 1272/2008.