Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key 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:
other: Study conducted according to the appropriate OECD test guideline and in compliance with GLP.

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

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)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Induction applications: neat
Challenge: 25%
Challengeopen allclose all
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
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:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% TS. 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:
25% TS
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: 25% TS. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

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:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.