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Administrative data

Description of key information

The key skin sensitisation study with dodecamethylcyclohexasiloxane (D6), conducted according to OECD Test Guideline 406 and in compliance with GLP, concluded that D6 was not sensitising to skin (NOTOX, 1999e).

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
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 Buehler/Guinea Pig Maximisation test method, conducted in 1999.
Species:
guinea pig
Strain:
other: Himalayan, albino
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd, Basel, SWITZERLAND
- Age at study initiation: 5 wk
- Weight at study initiation: <500 g
- Housing: 5/metal cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (unspecified deviations from this value said not to affect findings)
- Humidity (%): 50 (unspecified deviations from this value said not to affect findings)
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12 h/12 h
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
Concentrations:
INDUCTION
Intradermal - test group: 1:1 FCA saline; 100% TS; 1:1 Test substance in FCA
Intradermal - control group: identical but Test substance replaced by corn oil
Topical - test group: 100% Test substance
Topical - control group: corn oil
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
CHALLENGE:
1ST - 100% test substance
2ND - 20% and 50% test substance
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
test = 10
control = 5
Details on study design:
RANGE FINDING TESTS:
primary irritation phase: intradermal (2 animals) 10, 20, 50, 100% tested in corn oil ; topical (4 animals) 10, 20, 50, 100% tested in corn oil

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal-3 paired injections, topical)
- Exposure period: topical 48 hours
- 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; 100% TS ; 1:1 TS in FCA
Intradermal - control group: identical with TS replaced by corn oil
24 hours before topical induction 10% sodium dodecyl sulfate was applied to induce mild inflammation
Topical - test group: 100% TS
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: 100% TS; corn oil
- Evaluation (hr after challenge): 24 and 48 h following patch removal

C. RECHALLENGE: No conclusion on the skin sensitisation potential of the test substance could be drawn from the first challenge results since comparable reactions were observed at the test and control animals.
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day(s) of challenge: day 29
- Exposure period: 24h
- Test groups: 10
- Control group: +ve 10; -ve 5
- Site: flank
- Concentrations: 59% and 20% TS in corn oil
- Evaluation (hr after challenge): 24 and 48 h following patch removal
Challenge controls:
see above
Positive control substance(s):
yes
Remarks:
alpha hexylcinnamic aldehyde (10% aqueous)
Positive control results:
See table 1, below.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% test substance
No. with + reactions:
1
Total no. in group:
5
Remarks on result:
not determinable
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle 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:
100% test substance
No. with + reactions:
1
Total no. in group:
5
Remarks on result:
not determinable
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Vehicle 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:
100% test substance
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
not determinable
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Vehicle 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:
100% test substance
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
not determinable
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Vehicle corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50% test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50% test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
50% test substance
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
50% test substance
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
20% test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
20% test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
20% test substance
No. with + reactions:
1
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
20% test substance
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:
10% in water alpha-cinnamic aldehyde
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:
10% in water alpha-cinnamic aldehyde
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
positive control
Dose level:
10% in water alpha-cinnamic aldehyde
No. with + reactions:
7
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 (AFTER 6h CHALLENGE)

SKIN REACTIONS NUMBERS OF ANIMALS (SCORE)

 

NO. ANIMALS

Challenge – test group

TS (100%)

24h

2(1)

10

48h

3(1)

10

Vehicle (corn oil)

24h

0

10

48h

0

10

Challenge – control group

TS (100%)

24h

1(1)

5

48h

1(1)

5

Vehicle (corn oil)

24h

0

5

48h

0

5

Re-challenge – test group

TS (50%)

24h

0

10

48h

0

10

TS (20%)

24h

0

10

48h

0

10

Re-challenge – control group

TS (50%)

24h

0

5

48h

0

5

TS (20%)

24h

1

5

48h

0

5

Positive control (alpha-cinnamic aldehyde)*

10% in water

24h

8(2); 2(1)

10

48h

9(2); 1(1)

10

72 h

7(2); 3(1)

10

Vehicle (water)

24h

0

10

48h

0

10

72 h

0

10

* The control group of 5 animals for the positive control test produced the following reactions at 24, 48 and 72 h: 4(1), 3(1), 1(1).

No conclusion regarding sensitization could be drawn from the first challenge which produced responses in both the control and test group that were believed to indicate an irritation response. There was no indication of sensitization from the second challenge.

Interpretation of results:
GHS criteria not met
Conclusions:
The skin sensitisation study with dodecamethylcyclohexasiloxane (D6), conducted according to OECD Test Guideline 406 and in compliance with GLP, found no indication of sensitisation potential following challenge applications of 20% and 50% of the test material in corn oil. An earlier challenge using the neat material was discounted as responses believed to indicate irritation were seen in the control and test groups.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The key skin sensitisation study with dodecamethylcyclohexasiloxane (D6) was conducted according to OECD Test Guideline 406 and in compliance with GLP (NOTOX, 1999e).

At induction, the undiluted test material was applied intradermally and epidermally to 10 guinea pigs. The intradermal induction on study day 0 was followed by an epidermal induction on study day 7. 24 Hours before topical induction 10% sodium dodecyl sulfate was applied onto the skin to induce mild inflammation. The control group of 5 animals was treated similarly, but with the vehicle corn oil alone. Two weeks following the epidermal application, all animals were challenged with the undiluted test substance and the vehicle. A second challenge was performed one week later with 50% and 20% test substance concentrations.

Following the first challenge, grade 1 skin reactions were observed in three test and one control animals. No conclusion on the skin sensitisation potential of the test substance could be drawn from the first challenge results since comparable reactions were observed at the test and control animals. In the second challenge, no skin reactions were evident after the challenge exposure in the experimental animals to the 50% and 20% test substance concentration. Based on the results from the second challenge, D6 was concluded to be not sensitising to skin. The positive control substance was alpha hexylcinnamic aldehyde (10% aqueous) and gave the expected results.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the reliable in vivo data, D6 does not require classification for skin sensitisation according to Regulation (EC) No. 1272/2008.

No data are available regarding respiratory sensitisation.