1,1,1,3,5,5,5-heptamethyltrisiloxane

Endpoint summary

Description of key information

No skin sensitization data are available for the registered substance 1,1,1,3,5,5,5,-heptamethyltrisiloxane, therefore good quality data for the related substance octamethyltrisiloxane (L3, CAS 107-51-7) have been read-across.

In a key skin sensitization study conducted according to OECD Test Guideline 406 and in compliance with GLP, octamethyltrisiloxane was not sensitising to the skin of guinea-pig (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 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 OECD Test Guideline 406l, and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No skin sensitization data were available for the registered substance, 1,1,1,3,5,5,5,-heptamethyltrisiloxane, therefore the key study for the structurally analogous substance octamethyltrisiloxane (L3,CAS 107-51-7) was used as read across.

Octamethyltrisiloxane has been tested in a Guinea-Pig Maximisation test conducted according to OECD Test Guideline 406. During the induction phase the guinea-pigs (10 test group and 5 control group, males and females) were injected intradermally with 5% test substance in olive oil and in an emulsion of FCA/physiological saline and thereafter, topically treated with 100% test substance.

After a latency of 14 days, to allow a potential reaction of the immune system, the animals were challenged with 50% of the test substance in olive oil under occlusive dressing. The animals of the control were induced with olive oil and FCA/physiological saline and challenged similarly to those of the test group. Cutaneous reactions, i.e., erythema and eschar, as well as oedema formation were evaluated at 24 and 48 hours after removal of the dressing. No toxic symptoms were evident in the guinea pigs of the control or the test group. No deaths occurred. None of the animals of the tes group were observed with erythematous reactions after treatment with a test article concentration of 50% in olive oil. Therefore the test article is considered not to be a sensitizer when used under the described test conditions.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data from the structurally analogous substance octamethyltrisiloxane (L3, CAS 107-51-7), the registered substance 1,1,1,3,5,5,5,-heptamethyltrisiloxane does not require classification in accordance with Regulation (EC) No 1272/2008.