Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
1a The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP. The details given in this EPSR are taken from IUCLID 2007; however, there were sufficient details presented to conclude that the study was a reliable guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trimethoxysilane
No further details in IUCLID summary

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
No data in IULCID summary.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
cotton seed oil
Concentration / amount:
1st application: Induction 0.1 ml intracutaneous
2nd application: Induction 25 % occlusive epicutaneous
3rd application: Challenge 2.5 % open epicutaneous
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
cotton seed oil
Concentration / amount:
1st application: Induction 0.1 ml intracutaneous
2nd application: Induction 25 % occlusive epicutaneous
3rd application: Challenge 2.5 % open epicutaneous
No. of animals per dose:
10/sex/group
Details on study design:
The concentration of test material used for challenge was selected based on the results of range-finding experimentation in the Primary Irritation Phase. 
A Test Group of ten male and ten female guinea pigs was dosed with multiple intradermal injections on study day 0 and topical application on study day 7 to attempt to induce a sensitized state for evaluation of delayed contact hypersensitivity. 

1st application: Induction 0.1 ml intracutaneous
2nd application: Induction 25 % occlusive epicutaneous
3rd application: Challenge 2.5 % open epicutaneous

Intradermal induction consisted of injections of 5% Trimethoxysilane in cottonseed oil, 5% Trimethoxysilane in a 1:1 mixture of Freund's Complete Adjuvant (FCA): cottonseed oil and FCA. Topical induction consisted of a 48-hour occluded dermal exposure to 25% Trimethoxysilane. Fourteen days after topical induction, challenge dosing for detection of sensitization was performed.  
For challenge dosing, an essentially nonirritating concentration (2.5%) of the test material was applied topically under occlusion for 24 hours. Vehicle control sites were also dosed at challenge for detection of potential dermal reactions related to the vehicle. A Positive Control Group of five male and five female guinea pigs was included to verify the reliability of the test system.  The Positive Control Group was induced and challenged on a similar regimen as the Test  Group using dinitrochlorobenzene (DNCB) in 80% ethanol as the positive control material. Separate sites were dosed with 80% ethanol to detect any reactions related to the vehicle. Reactions to challenge exposures were evaluated at approximately 24 and 48 hours after dosing for all groups. Body weights were recorded prior to study initiation and at termination.
Challenge controls:
A Negative Control Group of five male and five female guinea pigs was dosed with the vehicle during induction and in the same manner as the Test Group at challenge and served as irritation controls.
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene (DNCB)

Study design: in vivo (LLNA)

Statistics:
No data in IUCLID summary.

Results and discussion

Positive control results:
Based on the Sensitization Incidence Index of 100 %, the positive control material, DNCB, was found to be an extreme sensitizing agent in the albino guinea pig under the conditions of this study, thereby verifying the reliability of the test system.  The positive control vehicle, 80% ethanol, was demonstrated to be nonsensitizing under the conditions of this study.

Any other information on results incl. tables

There were no deaths, clinical findings or remarkable body weight changes.

There were no sensitization reactions in the Test Group following challenge, and the Sensitization Incidence Index
was calculated to be 0%. Based on these results, the test material, Trimethoxysilane, was found to be a nonsensitizer
in albino guinea pigs under the conditions of this study. The test material vehicle, cottonseed oil, was also found to be nonsensitizing under the conditions of this study.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
In a GLP, OECD 406 skin sensitisation study (reliability score 1), trimethoxysilane was not sensitising to the skin of guinea-pigs.
Executive summary:

In a GLP, OECD 406 skin sensitisation study (reliability score 1), a test group of ten male and ten female guinea pigs was dosed with multiple intradermal injections on study day 0 and topical application on study day 7 to attempt to induce a sensitized state for evaluation of delayed contact hypersensitivity.  Intradermal induction consisted of injections of 5% Trimethoxysilane in cottonseed oil, 5% Trimethoxysilane in a 1:1 mixture of Freund's Complete Adjuvant (FCA): cottonseed oil and FCA. Topical induction consisted of a 48-hour occluded dermal exposure to 25% Trimethoxysilane. Fourteen days after topical induction, challenge dosing for detection of sensitization was performed.   For challenge dosing, an essentially nonirritating concentration (2.5%) of the test material was applied topically under occlusion for 24 hours. Vehicle control sites were also dosed at challenge for detection of potential dermal reactions related to the vehicle. A positive control group (using dinitrochlorobenzene) of five male and five female guinea pigs was included to verify the reliability of the test system.  There were no deaths, clinical findings or remarkable body weight changes.There were no sensitization reactions in the test group following challenge, and the Sensitisation Incidence Index was calculated to be 0%. Based on these results, trimethoxysilane, was found to be a nonsensitizer in albino guinea-pigs under the conditions of this study. The vehicle, cottonseed oil, was also found to be nonsensitising under the conditions of this study.