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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:
supporting study
Study period:
Pretest: 05.08.1996 to 08.08.1996. Main test: 07.10.1996 to 06.11.1996
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:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): DYNASYLAN PTMO
- Substance type: Alkoxysilane
- Physical state: Colourless liquid
- Stability under test conditions: at least one year
- Storage condition of test material: inert atmosphere

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 : Ad libitum
- 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

IN-LIFE DATES: Pretest: 05.08.1996 to 08.08.1996. Main test: 07.10.1996 to 06.11.1996

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Induction applications: neat
Challenge: 25%
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Induction applications: neat
Challenge: 25%
No. of animals per dose:
20 (test group); 10 (control)
Details on study design:
RANGE FINDING TESTS: conducted with groups of 3 animals.
Applications (6h 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: 6h
- Test groups: 20
- Control group: 10
- Frequency of applications: application on days 0, 7, 14
- Concentrations: TS neat or vehicle (corn oil) applied to the test and control groups, respectively (0.3 cc applied to a 2x2 cm patch)

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day(s) of challenge: day 28
- Exposure period: 6h
- Test groups: 20
- Control group: 10
- Site: flank
- Concentrations: 25% TS in corn oil and neat corn oil applied to both the test and control groups.
- Evaluation (hr after challenge): 24 and 48 h following patch removal

Challenge controls:
25% TS in corn oil and neat corn oil applied to both the test and control groups.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazol

Study design: in vivo (LLNA)

Statistics:
Not required.

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
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25% TS
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25% TS
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no 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:
GHS criteria not met
Conclusions:
In a guinea pig skin sensitisation study (Buehler test), conducted according to OECD 406 and to GLP (reliability score 1) trimethoxypropylsilane was not a skin sensitiser.