Tetradecamethylhexasiloxane

Endpoint summary

Description of key information

The key study for skin irritation is read across from a structurally analogous substance octamethyltrisiloxane (CAS 107-51-7). The study, conducted according to OECD TG 406, and in compliance with GLP, reports the test material to be not sensitising to skin (RCC, 1999).

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

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 Buehler/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): 17-23
- 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)

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 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 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

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

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

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:

The key study for skin sensitisation is read across from a structurally analogous substance octamethyltrisiloxane (L3, CAS 107-51-7). The study, conducted according to OECD TG 406, and in compliance with GLP, reports the test material to be not sensitising to skin (RCC, 1999).

At induction, 0.3 ml of undiluted test material was applied epidermally onto the scapular area of 10 guinea pigs. The area was shaved prior to application. The test material was kept in contact to the skin by occlusive dressing for 48 hours. 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. 0.3 ml of olive oil was applied onto the skin of the 5 control guinea pigs.

At challenge, 0.2 ml of 50 % of the test material in olive oil was applied onto the flanks of 10 test guinea pigs and kept in contact to the skin under occlusive dressing for 24 hours. The area was shaved prior to application. 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. Olive oil was applied onto the skin of the 5 control guinea pigs. No signs of erythema or oedema were observed at 24 and 48 hours post-application. Expected reactions were observed in the positive and negative control groups.

READ-ACROSS JUSTIFICATION

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint. In the case of sensitisation relevant properties are structural similarity, hydrolysis rate and the physical-chemical parameters in the same range. In the following paragraphs the proposed read-across is discussed. Further information can be found in the supporting report (PFA, 2013u) attached in Section 13 of the IUCLID 6 dossier.  

Read-across hypothesis

The hypothesis is that the target (registered) source substance and the (read-across) substances have similar toxicological properties because they are linear siloxanes with similar physicochemical properties and are structurally similar with similar hydrolysis rates so have similar toxicological properties.

a) Structural similarity

Tetradecamethylhexasiloxane (L6) is a methyl-substituted linear siloxane, with six silicon atoms connected by five oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. Octamethyltrisiloxane (L3) is also a methyl substituted linear siloxane, with three silicon atoms and two oxygen atoms.

b) Similar physicochemical properties

The linear siloxanes all have high log K_ow (increasing with increasing chain length) and low water solubility.

c) Similar hydrolysis rates

The linear siloxanes all hydrolyse slowly at neutral pH.

Summary of key sensitisation data for linear siloxanes

Substance	L2	L3	L4	L5	L6
Chemical name	Hexamethyl disiloxane	Octamethyl trisiloxane	Decamethyl tetrasiloxane	Dodecamethyl pentasiloxane	Tetradecamethyl hexasiloxane
CAS number	107-46-0	107-51-7	141-62-8	141-63-9	107-52-8
Skin sensitising result	Not sensitising (Dow Corning Corporation, 1992)	Not sensitising (RCC, 1999)	-	-	-

Reference

Dow Corning Corporation (1992). Human repeated insult patch test with hexamethyldisiloxane. TKL Research, USA. Report no.: 1992-I0000-37036. Report date: 1992-03-11.

PFA, 2013u, Peter Fisk Associates, Analogue report - mammalian toxicity of linear and branched siloxanes, PFA.300.002.008

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available information on the read across substance, octamethyltrisiloxane (CAS 107-51-7), no classification for skin sensitisation is required according to Regulation (EC) No 1272/2008.