Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000-03-30 to 2000-05-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not stated
- Age at study initiation: 5-8 weeks
- Weight at study initiation: 445-518 g
- Housing: Animals were housed in groups of five in suspended metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.5 to 22.5
- Humidity (%): 31-52
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: Alembicol D
Concentration / amount:
25 and 50 % (v/v) in Alembicol D
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Concentration / amount:
25 and 50 % (v/v) in Alembicol D
No. of animals per dose:
Forty male guinea-pigs
Details on study design:
RANGE FINDING TESTS: The animals for the preliminary investigations w ere clipped and shaved the day prior to dosing and the animals for the topical irritancy investigations were re-shaved on the day of dosing. The procedure employed for these investigations were as follows: Intradermal injections - A range of concentrations of the test substance in Alembicol D were injected intradermally (0.I-ml/site) into the clipped left flank of two guinea pigs (per level tested) using a 1 ml plastic syringe and 26 G needle. The resulting dermal responses w ere assessed approximately 24, 48 and 72 hours later.
Topical application - Patches of Whatman No. 3 paper (20 mm x 20 mm) were saturated (volume approximately 0.2ml) with a range of concentrations of the test substance in Alembicol D and applied to the clipped and shaved flanks of each of four guinea-pigs. The patches w ere covered by a strip of "Blenderm" and firmly secured by "Elastoplast" wound round the trunk and fixed with 'sleek impervious plastic adhesive tape. The dressings were removed after an exposure period of approximately 24 hours and the reaction sites were assessed for erythema and oedema. Further examination of the sites was carried out approximately 24 and 48 hours after removal of the dressings.
Based on the results of the preliminary investigations the following concentrations of compound were selected:
Induction intradermal injection - l% vlv in Alembicol D. This was the highest concentation that caused slight irritation but did not adversely affect the animals.
lnduction topical application - as supplied. The test material applied topically as supplied by the Sponsor produced mild to moderate irritation but did not adversely affect the animals.
Topical challenge - 50 and 25% vlv in Alembicol D. From preliminary investigations 50 v/v in Alembicol D was the highest concentration not giving rise to irritating effects


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Two (intradermal injection and topical application)
-Test groups: FCA, TS in FCA (50:50 mixture), TS in Alembicol D
- Exposure period: Topical application left for 48 hours, 1 week after intradermal injections.
- Control group: Treated similarly to test animals with the exception that the test substance was omitted. Since there was no vehicle used, the negative control animals received a dry patch. Positive controls received 10% v/v hexyl cinnamic aldehyde (in Alembicol D for the injections) instead of the test substance.
- Site: Scapular region
- Concentrations: Unchanged test substance


B. CHALLENGE EXPOSURE:
- No. of exposures: One
- Day(s) of challenge: Two weeks after the topical induction application.
- Exposure period: Patches were sealed for 24 hours.
- Test groups: 0.2 ml TS in 50% v/v Alembicol D (anterior site), TS in 25% v/v Alembicol D (middle site), Alembicol D only (posterior site).
- Control group: Positive control: HCA in 50% v/v Alembicol and Alembicol only.
- Site: Left flank
- Evaluation (hr after challenge): Observations for clinical effects were conducted on days 1, 7 and 21 after challenge. Challenge sites were evaluated 24 and 48 hours after removal of patches.
Challenge controls:
Negative controls: 0.2 ml of 50 % test material v/v in Alembicol D was applied to the anterior site, 25 % test material v/v in Alembicol D was applied to the middle site and Alembicol D to the posterior site.
Positive controls: Undiluted HCA was applied to the anterior site, 50 % v/v HCA in Alembicol D to the middle site and the vehicle Alembicol D to the posterior site.
Positive control substance(s):
yes
Remarks:
hexyl cinnamic aldehyde

Results and discussion

Positive control results:
Intradermal injections: Slight to well defined erythema was observed in positive control animals following topical application with neat hexyl cinnamic aldehyde.
Challenge: All five positive control animals produced evidence of skin sensitisation.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 %, 50 % v/v test material in Alembicol D, and Alembicol D alone
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:
negative control
Dose level:
25 %, 50 % v/v test material in Alembicol D, and Alembicol D alone
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:
test group
Dose level:
25 and 50% v/v in Alembicol D
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25 and 50% v/v in Alembicol D
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
HCA undiluted, 50 % v/v HCA in Alembicol D, and Alembicol D alone
No. with + reactions:
4
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
HCA undiluted, 50 % v/v HCA in Alembicol D, and Alembicol D alone
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In the skin sensitisation study, conducted according to OECD 406, and in compliance with GLP, the test material, 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane, was reported to be not sensitising to the skin of any of the test animals.
Executive summary:

Based on the results of a preliminary study and in compliance with the guideline, an intradermal injection of Dow Corning 704 Diffusion Pump Fluid and 1% v/v in Alembicol D, followed by a topical application of Dow Corning 704 Diffusion Pump Fluid (as supplied) and then a challenge application of Dow Corning 704 Diffusion Pump Fluid, 50 % and 25% v/v in Alembicol D, were administered to guinea-pigs to determine the skin sensitising potential of Dow Corning 704 Diffusion Pump Fluid. Twenty test and ten control guinea-pigs were used in the main study, and five vehicle control and five positive control animals were used in the positive control study. In this study Dow Corning 704 Diffusion Pump Fluid did not produce evidence of skin sensitisation in any of the test animals. All animals in the positive control group produced evidence of skin sensitisation following treatment with hexyl cinnamic aldehyde.