Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 March 2015 to 30 April 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD guideline and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test

Test material

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

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Crl: HA
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 5 weeks old
- Weight at study initiation: 355 - 421 g
- Housing: The animals were kept in groups in Terluran - cages on Altromin saw fibre bedding (preliminary test and main study lot no. 02102150227).
- Diet: ad libitum autoclaved hay and Altromin 3122 maintenance diet for guinea pigs (preliminary test and main study lot no. 0830), rich in crude fibre.
- Water: ad libitum tap water (drinking water, municipal residue control, microbiological controls at regular intervals).
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): at least 10
- Photoperiod: 12 hours light, 12 hours dark.

IN-LIFE DATES: To: 30 April 2015

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
100% for the dermal inductions; 75% for the challenge application.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
100% for the dermal inductions; 75% for the challenge application.
No. of animals per dose:
preliminary test: 4
main test group: 20
negative-control group: 10
Details on study design:
RANGE FINDING TESTS:
2 animals were treated topically with concentrations of 100% and 75% of the test item (dissolved in corn oil) for 6 hours.
Based on the results of this preliminary test the following concentrations were chosen for the main test:
100% for the dermal inductions (highest possible concentration that produced mild irritation)
75% for the challenge application (maximum non-irritant concentration)

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three
- Exposure period: 6 hours
- Test groups: 20 animals induced with 100% test substance.
- Control group: 10 animals received similar treatment with no test substance.
- Site: The left flank was cleared of hair (close-clipped) prior to the first application and again prior to further applications. A gauze patch was loaded with 0.5 mL of the test substance. The patch was applied to the test area of approximately 2.5 x 2.5 cm and was held in contact with the help of an occlusive dressing for 6 hours.
- Frequency of applications: weekly at the same site.
- Duration: three weeks
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: one exposure, fourteen days after the last induction
- Exposure period: 6 hours
- Test groups: 14 days after the last induction application the prepared test substance was applied to an area of approximately 2.5 x 2.5 cm on the right flank and was held in contact with the help of an occlusive dressing for 6 hours.
- Control group: A patch loaded with the vehicle was applied to an area of approximately 2.5 x 2.5 cm on the left flank (intraspecific control) and was held in contact with the help of an occlusive dressing for 6 hours.
- Site: Both flanks were cleared of hair (close-clipped) prior to the challenge application.
- Concentrations: 75%
- Evaluation (hr after challenge): Approximately 21 hours after removing the patch, the challenge area was cleaned and cleared of hair by use of a depilatory cream. Approximately 24 and 48 hours after removing the patch the skin reaction was observed and recorded.
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole. The most recent reliability check was performed in November/December 2014.

Results and discussion

Positive control results:
The sensitisation rate after application of the positive-control substance mercaptobenzothiazole (25% in vaseline) was 60%, confirming the reliability of the test system.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Any other information on results incl. tables

All animals of both groups survived throughout the test period. No signs of toxicity were recorded. The body weight development of all animals was within the range of variation for this strain.

Results of the Induction phase:

Reading

Hours after challenge

Group

Dose level

No. with + reactions

Total no. in group

Clinical observations

other: Induction 1

24

test group

100%

10

20

Erythema Grade 1

other: Induction 2

24

test group

100%

7

20

Erythema Grade 1

other: Induction 3

24

test group

100%

9

20

Erythema Grade 1

other: Induction1, 2 and 3

48

test group

100%

0

20

No signs of irritation observed

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Tris(isopropenyloxy)(vinyl)silane has been tested in a guinea-pig maximisation (Buehler) study conducted according to OECD 406 and in compliance with GLP. None of the animals challenged for 6 hours to the test item or the negative control showed any evidence of sensitisation at either 24 or 48 hours after removing the patch.