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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
The restriction was that the starting concentration selected for induction was not the highest to cause mild-to-moderate skin irritation as required by OECD TG 406.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The non-LLNA in vivo test was already available so a new test was not conducted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Methyltrimethoxysilane (CAS 1185-55-3)

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elm Hill Breeding Labs, Inc. Chemlmsford, MA.
- Age at study initiation: 21-67
- Weight at study initiation: 353.1-468.3 grams
- Housing: group housed, suspended stainless steel cages
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68 +/- 5
- Humidity (%): 30-70
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
Test article: 50% at both induction and challenge.
Positive control: 0.1% DNCB in 95% EtOH.
Challenge
Route:
epicutaneous, semiocclusive
Vehicle:
polyethylene glycol
Concentration / amount:
Test article: 50% at both induction and challenge.
Positive control: 0.1% DNCB in 95% EtOH.
No. of animals per dose:
Experimental: 10 males, 10 females
Negative controls: 5 males, 5 females
Positive controls: 3 males, 2 females
Preliminary irritation 1 male, 2 females
Details on study design:
RANGE FINDING TESTS:

Preliminary irritation study was performed with 3 naive animals.
10%, 15%, 25% and 50% dilutions were applied to the skin for 6 hours. the substance was found not irritating at the highest concentration, so this was selected for the main test.

MAIN STUDY
A. INDUCTION EXPOSURE

- Days 0. 7 and 14.
- Closed patches were applied directly to the skin using a chamber, the chamber was kept in place with occlusive bandaging. The patch was removed after 6 hours of exposure and residual article was washed off with water.
- The test article was applied once per week for 3 consecutive weeks (days 0, 7 and 14) on one side of the animal. The positive control was applied in the same manner. Naive animals, untreated during induction phase, served as negative control group

B. CHALLENGE EXPOSURE

-Day 28
- on the day of challenge, a 4x3 cm naive skin site was shaved on the flanks of the experimental and control animals
- the challenge test was conducted in a manner identical to the induction exposure
- the test site was examined for erythema and oedema ca. 3 hours after removal of the challenge dose, and repeated ca. 24 hours thereafter (according to M&K grading scale)

Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
DNCB

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
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:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1%
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1%
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:
The test material was found not sensitising to guinea pig skin in a Buehler test, conducted according to current OECD test guideline with acceptable restrictions. The restriction was that the starting concentration selected for induction was not the highest to cause mild-to-moderate skin irritation as required by OECD TG 406.