Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The key in vivo skin irritation study, conducted according to FDA Handbook Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, but prior to GLP, the test material, trimethoxy(vinyl)silane, was concluded to be not irritating to skin (Consultox Laboratories, 1976).

In the in vivo eye irritation study, conducted according to OECD Test Guideline 405 and in compliance with GLP, the test material, trimethoxy(vinyl)silane, was concluded to be not irritating to eyes (Pharma Entwicklung Toxikologie, 1991).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
not conducted in compliance with GLP
Qualifier:
according to guideline
Guideline:
other: FDA Handbook Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
No data available.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 0.5ml of the test substance was applied to both the intact and abraded skin.

- Concentration (if solution): undiluted

Duration of treatment / exposure:
24 hour(s)
Observation period:
72 hours
Number of animals:
4
Details on study design:
TEST SITE

- Area of exposure: the back of the animal

- % coverage: unspecified.

- Type of wrap if used: The test areas were occluded by means of one inch gauze pads secured with adhesive tape and further occluded with a 'stockinette' sleeve covering the entire trunk of the animal.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): no data, but after 24 hours the patches were removed and the resultant reactions evaluated.


SCORING SYSTEM: Draize scale.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There were no signs of erythema or edema at any time point. The Primary Irritation Index was 0.0.  The test material was a non-irritant under these conditions.
Other effects:
No other effects reported.

All values were zero at all recorded time points.

Interpretation of results:
GHS criteria not met
Conclusions:
The in vivo skin irritation study, conducted according to FDA Handbook Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, but prior to GLP, the test material, trimethoxy(vinyl)silane, was concluded to be not irritating to skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Source: Hoechst AG, Kastengrund

- Age at study initiation: 3-5 months

- Weight at study initiation: 2.2-3.9 kg

- Housing: Individually caged

- Diet: Altromin 2123 rabbit feed (GmbH), ad libitum

- Water: ad libitum



ENVIRONMENTAL CONDITIONS

- Temperature (°C): 18 (± 3)

- Humidity (%): 55 (±20)

- Air changes (per hr): The report states that the room was air-conditioned.

- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as a control
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 0.1ml

- Concentration (if solution): undiluted


Duration of treatment / exposure:
24 hour(s)
Observation period (in vivo):
1, 24, 48, 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): Yes, with a saline solution at 37C.

- Time after start of exposure: 24 h


SCORING SYSTEM: The Draize scale


TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The conjunctiva of the animals showed marked hyperaemia and redness. Slight conjunctival swelling was evident. Irritation was only observed 30 - 60 minutes post application; all effects were reversible within 1 day.
Other effects:
None reported.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0 

2/1/2 

1/1/0 

24 h

 0/0/0

 0/0/0

0/0/0 

0/0/0 

48 h

 0/0/0

 0/0/0

 0/0/0

 0/0/0

72 h

 0/0/0

 0/0/0

 0/0/0

 0/0/0

Average 24h, 48h, 72h

 0

0

0

Reversibility*)

 -

Average time (unit) for reversion

 

 

 24h

24h 

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Conclusions:
In the in vivo eye irritation study, conducted according to OECD Test Guideline 405 and in compliance with GLP, the test material, trimethoxy(vinyl)silane, was concluded to be not irritating to eyes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

The key in vivo skin irritation study, conducted according to FDA Handbook Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics prior to GLP, the test material, trimethoxy(vinyl)silane, was concluded to be not irritating to skin (Consultox Laboratories, 1976). In the study, 0.5 mL of the undiluted test substance, trimethoxy(vinyl)silane, was applied onto the shaved skin of 4 rabbits for 24 hours under occlusive dressing. Following test patch removal, the skin reactions of each animal were evaluated at 24 and 48 hours. There were no signs of erythema or oedema at any time point. The Primary Irritation Index was 0.0.

A reliable supporting study was conducted using a protocol similar to OECD Test Guideline 404, but not in compliance with GLP (Bushy Run Research Center, 1984). Trimethoxy(vinyl)silane was concluded to be moderately irritating under the conditions tested, however, based on the available information, the substance does not meet the current EU criteria for classification as a skin irritant.

Two reliability 4 studies were also available which support the key data, reporting mild or no irritation (Marhold, 1986; Dow Corning Corporation, 1973).

In the key in vivo eye irritation study, conducted according to OECD Test Guideline 405 and in compliance with GLP, the test material, trimethoxy(vinyl)silane, was concluded to be not irritating to eyes (Pharma Entwicklung Toxikologie, 1991). In the study, 0.1 mL of the undiluted test substance, trimethoxy(vinyl)silane, was instilled into the eyes of 3 rabbits. Following 24 hours of exposure, the eye irritation reactions of each animal were evaluated at 24, 48 and 72 hours. The conjunctiva of the animals showed marked hyperaemia and redness. Slight conjunctival swelling was evident. Irritation was only observed 30-60 minutes post application; all effects were reversible within 1 day.  

Two reliable supporting studies also found the test material not irritating to rabbit eyes (Bushy Run Research Center, 1984; Consultox Laboratories, 1976). Two reliability 4 studies for eye irritation were also available (Dow Corning Corporation, 1973; Mellon, 1962).

Justification for classification or non-classification

Based on the available data, trimethoxy(vinyl)silane does not require classification for irritation according to Regulation (EC) No 1272/2008.