Hexamethylcyclotrisiloxane

Endpoint summary

Description of key information

In an in vivo skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, hexamethylcyclotrisiloxane (D3; CAS 541-05-9; EC No. 208-765-4) was not sensitising to the skin of guinea pigs (Harlan Laboratories Ltd., 2010).

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:

2009-10-12 to 2009-11-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

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.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg, GERMANY
- Age at study initiation: 4-6 wk
- Weight at study initiation: 359-445 g
- Housing: 1/Makrolon Type 4 cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 2 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 2009-10-12 To: 2009-11-06

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Concentration / amount:

induction: intradermal 15%; epidermal 50%
challenge epidermal: 10%

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

induction: intradermal 15%; epidermal 50%
challenge epidermal: 10%

No. of animals per dose:

test: 10
vehicle control: 5
postitive control: 10

pretest intradermal: 1
pretest epidermal: 2

Details on study design:

RANGE FINDING TESTS:
intradermal 5, 10, 15% tested in corn oil (15% was the maximum technically feasible), 1 wk following following 1:1 FCA:saline [15% was selected as highest concentration technically possible, well tolerated systemically and causing mild skin irritation.]
epidermal 10, 15, 25, 50% in corn oil (50% was the maximum technically feasible). [50% (highest techincally possible and causing mild to moderate skin irritation) was chosen for induction and 10% (the highest non-irritant concentration) was chosen for challenge.]

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal-3 paired injections, topical)
- Exposure period: topical 48h
- Test groups: 10
- Control group: +ve 10; -ve 5
- Site: two rows of 3 sites, one row either side of dorsal mid-line
- Frequency of applications: intradermal treatment day 0; topical induction day 7
- Duration: induction period continues to day 21
- Concentrations:
Intradermal - test group: 1:1 FCA saline; 15% TS in corn oil; 15% TS in 1:1 FCA:saline
Intradermal - control group: 1:1 FCA saline; corn oil; 1:1 FCA:saline
Topical - test group: 50% TS in corn oil
Topical - control group: corn oil

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day(s) of challenge: day 22
- Exposure period: 24h
- Test groups: 10
- Control group: +ve 10; -ve 5
- Site: flank
- Concentrations: 10% TS in corn oil; corn oil
- Evaluation (hr after challenge): 24 and 48 h following patch removal

Challenge controls:

There were no responses from any vehicle controls at challenge (see table).

Positive control substance(s):

yes

Remarks:

3% alpha-hexylcinnamaldehyde (see table)

Positive control results:

One of ten animals showed skin reactions following challenge with 1% alpha-hexylcinnamaldehyde in PEG 300, with no responses in the control group. Eight of ten responded to a 3% challenge at 24 h, and 9 of ten responded at 48 h, again there were no responses in the controls (see table).

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10% test substance in corn oil

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% test substance in corn oil

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

10% test substance in corn oil

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

10% test substance in corn 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 chemical

Dose level:

corn 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 chemical

Dose level:

corn oil

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:

corn 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:

corn 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:

positive control

Dose level:

1% alpha-hexylcinnamaldehyde in PEG 300

No. with + reactions:

1

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

1% alpha-hexylcinnamaldehyde in PEG 300

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:

positive control

Dose level:

3% alpha-hexylcinnamaldehyde in PEG 300

No. with + reactions:

8

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:

3% alpha-hexylcinnamaldehyde in PEG 300

No. with + reactions:

9

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Table 1: Incidence of dermal response to challenge dosing

GROUP	MATERIAL	INTERVAL	DERMAL SCORES*				SENSITIZATION INCIDENCE INDEX**	SEVERITY INDEX***
			0	1	2	3
Test	TS 10%	24h	10/10	0/10	0/10	0/10	0/10	0
		48h	10/10	0/10	0/10	0/10	0/10	0
	Corn oil	24h	10/10	0/10	0/10	0/10	0/10	0
		48h	10/10	0/10	0/10	0/10	0/10	0
Positive control	hexylcinnamaldehyde1%	24h	9/10	1/10	0/10	0/10	1/10	0.1
		48h	10/10	0/10	0/10	0/10	0/10	0
	hexylcinnamaldehyde3%	24h	2/10	8/10	0/10	0/10	8/10	0.8
		48h	1/10	9/10	0/10	0/10	9/10	0.9
Vehicle control	TS 10%	24h	5/5	0/5	0/5	0/5	0/5	0
		48h	5/5	0/5	0/5	0/5	0/5	0
	Corn oil	24h	5/5	0/5	0/5	0/5	0/5	0
		48h	5/5	0/5	0/5	0/5	0/5	0

Skin reactions were graded

0 no visible change

1 discrete or patchy erythema

2 moderate and confluent erythema

3 intense erythema and swelling

There were no signs of systemic toxicity during the study. All animals gained weight during the study and there were no significant test-article related differences in vehicle and test group mean body weight.

* Number of animals showing skin reactions at each of grades 0 -3

** Incidence Index = number of animals showing post-challenge skin reactions at either 24 or 48 hours, divided by the number of animals in the group

*** Severity Index = Sum of post-challenge test grades divided by the total number of animals tested.

 

Interpretation of results:

GHS criteria not met

Conclusions:

In an in vivo skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, hexamethylcyclotrisiloxane was not sensitising to the skin of guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In an in vivo skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, hexamethylcyclotrisiloxane was tested for its ability to induce skin sensitisation in 15 (10 test and 5 control) male albino guinea pigs. The dose levels used in the main test were based on the findings of intradermal and epidermal pretests.

At intradermal induction, 3-paired injections of 15% dilution of the test substance in corn oil and in an emulsion of Freund's Complete Adjuvant (FCA)/physiological saline were injected into the skin of the guinea pigs. The control animals were induced intradermally with corn oil and FCA/physiological saline only.

One week following the intradermal induction, an epidermal induction was performed where 50% of the test substance in corn oil was applied onto the skin for 48 hours under occlusive dressing. The control animals were induced epidermally in the same manner but by application of corn oil only.

Two weeks after the epidermal induction the control and test animals were challenged by epidermal application of the test substance at 10% in corn oil for 24 hours under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

Positive control animals were exposed to 1% alpha-hexylcinnamaldehyde in PEG 300 and 3% alpha-hexylcinnamaldehyde in PEG 300 and skin reactions were seen in 8 out of 10 animals at 24 hours and 9 out of 10 animals at 48 hours following epidermal exposure to 3% alpha-hexylcinnamaldehyde in PEG 300, confirming the validity of the study.

There were no skin reactions following challenge exposure in any of the test or control animals and hexamethylcyclotrisiloxane was not sensitising to the skin of guinea pigs (Harlan Laboratories Ltd., 2010).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

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