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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
Study period:
Pretest: 05 - 08 Aug 1996. Main test: 07 Oct - 06 Nov 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany
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, that was performed prior to the adoption of OECD 429.

Test material

Constituent 1
Chemical structure
Reference substance name:
Trimethoxypropylsilane
EC Number:
213-926-7
EC Name:
Trimethoxypropylsilane
Cas Number:
1067-25-0
Molecular formula:
C6H16O3Si
IUPAC Name:
trimethoxy(propyl)silane

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, GERMANY
- Age at study initiation: young adults
- Weight at study initiation: <500 g
- Housing: Makrolon Type IV, max 5/cage
- Diet: Ssniff G 4-diet for Guinea Pigs, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 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:
100%
Day(s)/duration:
3 single treatments (6 h exposure), Days 0, 7 and 14
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
25%
Day(s)/duration:
single treatment (6 h exposure), Day 28
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Pre-test: 6
Main test: 20 (test group); 10 (control)
Details on study design:
RANGE FINDING TESTS:
Applications (6 h occluded contact) of 5, 25, 50 and 100% TS with examination at 24 and 48 h following patch removal. 100% was identified as a suitable induction concentration (causing mild irritation), while 25% was identified as the lowest non-irritant challenge concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 dermal occlusive
- Exposure period: 6 h
- Test groups: neat test substance (0.3 mL applied to a 2x2 cm patch)
- Control group: verhicle corn oil (0.3 mL applied to a 2x2 cm patch)
- Site: left flank
- Frequency of applications: application on Days 0, 7, 14
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day(s) of challenge: Day 28
- Exposure period: 6 h
- Test groups: test substance in corn oil and corn oil only
- Control group: test substance in corn oil and corn oil only
- Site: posterior right flank (test substance) and anteriour right flank (vehicle)
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48 h following patch removal
Challenge controls:
The control group is actually a control.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazol (MCBT)

Results and discussion

Positive control results:
Response rate of 30% (3/10 animals) indicates that the standard allergen is a sensitizer in the guinea pig under the conditions of this study. (See table 1.)

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25% test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50% MCBT
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

Table 1: Incidence of dermal response to challenge dosing

GROUP

MATERIAL

INTERVAL (AFTER 6h CHALLENGE)

SKIN REACTIONS (NUMBER OF ANIMALS)

NUMBER OF ANIMALS

SENSITIZATION INCIDENCE INDEX**

Test

TS (25%)

24h

0

20

0/20=0%

48h

0

20

Vehicle

24h

0

20

0/20=0%

48h

0

20

Positive control (2-mercaptobenzothiazol)

50% MCBT in vehicle

24h

3

10

3/10=30%*

48h

0

10

Vehicle (Vaseline)

24h

0

5

0/5=0%

48h

0

5

Negative (vehicle) control

TS (25%)

24h

0

10

n/a

48h

0

10

Vehicle

24h

0

10

n/a

48h

0

10

* The response of 30% in the positive controls confirms that the standard allergen tested is sensitizing in guinea pig under the conditions of this study.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In a guinea pig skin sensitisation study (Buehler test), conducted according to OECD 406 and to GLP (reliability score 1) trimethoxy(propyl)silane was not a skin sensitiser.