Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
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.

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexamethyldisiloxane
EC Number:
203-492-7
EC Name:
Hexamethyldisiloxane
Cas Number:
107-46-0
Molecular formula:
C6H18OSi2
IUPAC Name:
hexamethyldisiloxane
Test material form:
other: liquid

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Induction
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.
Challenge
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

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
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.

Applicant's summary and conclusion

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.