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Skin sensitisation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler 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 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:
3-trimethoxysilylpropane-1-thiol
EC Number:
224-588-5
EC Name:
3-trimethoxysilylpropane-1-thiol
Cas Number:
4420-74-0
Molecular formula:
C6H16O3SSi
IUPAC Name:
3-trimethoxysilylpropane-1-thiol
Details on test material:
- Name of test material (as cited in study report): Dynasylan MTMO (3-trimethoxysilylpropane-1-thiol)
- Substance type: Organosilane
- Physical state: Liquid
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Stability under test conditions: >1 year
- Storage condition of test material: tightly closed containers, under an exhaust hood.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH
- Age at study initiation: 'young'
- Weight at study initiation: less than 500 g
- Housing:Conventional Type IV Makrolon cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days


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


Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
1st and 2nd induction used undiluted test substance, but the 3rd phase was diluted to 50% in corn oil due to severe skin irritation. The challenge phase used 25% test substance in corn oil.
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
1st and 2nd induction used undiluted test substance, but the 3rd phase was diluted to 50% in corn oil due to severe skin irritation. The challenge phase used 25% test substance in corn oil.
No. of animals per dose:
Test group: 20; control group: 10.
Details on study design:
RANGE FINDING TESTS: 2-3 hours before administration, the fur was mechanically removed from the left and right flanks of three animals. 0.3 cm3 of each of the test substance concentrations (5, 25 and 50% in corn oil and the undiluted test compound) were applied to patches of surgical gauze (2X2 cm). These patches were placed on the clipped flanks of each of the three animals. The patches were covered by a strip of an occlusive plaster and firmly secured by a bandage for six hours. Each animal received two patches on each flank (left, front: 5%; left, rear: 25%; right, front: 50%; right rear: 100%). After removal of the patch, the administration areas were cleared of residual test substance with corn oil. The dermal reactions were assessed 30 to 54 hours after start of treatment. In the 4th week of the test, three guinea-pigs, kept under the same conditions, but without treatment, were used to re-determine the maximum non-irritant concentration for the challenge treatment.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Test groups: one
- Control group: Induction Phases I-III vehicle (corn oil) only applied to left flank.
- Site: Left flank
- Frequency of applications: Day 0, Day 7 and Day 14
- Duration: 6 hours
- Concentrations: Phases I and II used undiluted, and Phase III used 50% in corn oil.


B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Day 28
- Exposure period: 6 hours
- Test and control groups: both treated with vehicle on front flank and 25% test substance on rear flank.
- Site: Right flank
- Concentrations: 25%
- Evaluation (hr after challenge): 30-54 hours

Challenge controls:
Ten animals treated with vehicle on front right flank, and 25% test substance on rear right flank.
Positive control substance(s):
not specified

Results and discussion

Positive control results:
No positive control

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
30
Group:
test chemical
Dose level:
25%
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
54
Group:
test chemical
Dose level:
25%
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
30
Group:
negative control
Dose level:
25%
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:
54
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Group:
positive control
Remarks on result:
other: positive control was not included

Any other information on results incl. tables

The test and control animals showed normal body weight gains throughout the study. No clinical signs of systemic effects were observed in any of the animals during the observation period. There were no skin reactions following induction Phase I. At 30 hours after induction Phase II there were minimum to intense skin reactions in all animals. Following induction Phase III, skin reactions were moderate to intense and were combined with eschar formation in most cases. Only one animal had a mild skin reaction. The control animals treated with the vehicle only, did not show any irritation after all three inductions. Following the challenge application there were skin reactions in eight animals: 30 hours post-application the animals had moderate to intense erythema and swelling; at 54 hours patchy to intense erythema and swelling. All 12 other test, and all control animals did not show any skin reactions 30 -54 hours after treatment.

A positive control was not included in this test. The laboratory did however confirm the sensitivity of the Dunkin-Hartley guinea-pig in their studies by conducting a Magnusson and Kligman Maximisation study with α-hexylcinnamaldehyde as the positive control.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
In a good quality skin sensitisation study (reliability score 1) conducted according to OECD test guidelines (Buehler test) and GLP, 3-trimethoxysilylpropane-1-thiol) was sensitising to the skin of Dunkin-Hartley guinea-pigs.
Executive summary:

3-Trimethoxysilylpropane-1-thiol was tested in a traditional Buehler skin sensitisation study, to GLP. Twenty Dunkin-Hartley guinea-pigs were exposed to three separate induction phases on their shaved left flanks. On Day 0 undiluted test substance was applied under an occlusive patch for six hours. On Day 7 this process was repeated. On Day 14 the process was repeated again, but with a 50% solution of test substance in corn oil. After each application the skin was monitored for reactions. Ten negative controls had patches with corn oil only applied to their left flanks. On Day 28 both negative controls and test animals had an occlusive patch of corn oil applied to their front right flanks, and an occlusive patch with 25% test substance (in corn oil) applied to their rear right flanks. After six hours the dressings were removed and the areas wiped with corn oil. The skin was then assessed at 30 and 54 hours after administration.

The test and control animals showed normal body weight gains throughout the study. No clinical signs of systemic effects were observed in any of the animals during the observation period. There were no skin reactions following induction Phase I. Following Phases II and III there was moderate to severe skin reactions. The control animals treated with the vehicle only, did not show any irritation after all three inductions. Following the challenge application there were skin reactions in eight animals: 30 hours post-application the animals had moderate to intense erythema and swelling; at 54 hours patchy to intense erythema and swelling. All 12 other test, and all control animals did not show any skin reactions 30 -54 hours after treatment. Therefore the the study authors concluded that 3-trimethoxysilylpropane-1-thiol is a skin sensitiser.