Registration Dossier

Administrative data

Description of key information

In the key skin irritation/corrosion study conducted according to OECD TG 404 and in compliance with GLP (Hazleton Laboratories, 1990) methylsilanetriyl triacetate was corrosive to the skin of rabbits. Severe erythema (Grade 4) was still apparent at the 14 day observation point, with necrosis. Maximum Grade 3 oedema was resolved by Day 14 in all animals.

In the key eye irritation/corrosion study conducted using a protocol similar to OECD TG 405, but not compliant to GLP (Hazleton Laboratories, 1970) methylsilanetriyl triacetate caused severe, irreversible damage to the eyes of rabbits.

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:
03.10.1989 to 17.01.1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France
- Age at study initiation: Adult
- Weight at study initiation: 2.4 to 2.6 kg
- Housing: Individually in polystyrene cages
- Diet (e.g. ad libitum): 150 g/animal/day
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 8 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20± 3
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03.10.1989 To: 17.10.1989
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
Four hours
Observation period:
14 days
Number of animals:
Three
Details on study design:
TEST SITE
- Area of exposure: Flanks
- % coverage: No data
- Type of wrap if used: Semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No done

SCORING SYSTEM: Equivalent to Draize
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Grade 4 erythema was observed on Day 14 for animal No. 1. Burns developed by 72 hours and remained on Day 14.
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Grade 2 edema was observed for animal No 1, which was fully reversible within 14 days.
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Burns developed immediately, and were replaced by eschar by Day 14 for animal No 2.
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Grade 1 edema was observed for animal No 2, which was fully reversible within 72 hours.
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Burns developed immediately, and were replaced by eschar by Day 14 for animal No 3.
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Grade 2.33 edema was observed for animal No 3, which was fully reversible within 14 days.
Irritant / corrosive response data:
Severe erythema (Grade 4) still apparent at 14 day observation, with necrosis. Max Grade 3 oedema, resolved by Day 14.
Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
In a skin irritation/corrosion study conducted according to OECD TG 404 and in compliance with GLP (reliability score 1) methylsilanetriyl triacetate was corrosive to the skin of rabbits. Severe erythema (Grade 4) was still apparent at the 14 day observation point, with necrosis. Maximum Grade 3 oedema was resolved by Day 14 in all animals.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.2- 2.9 kg
No further data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Observation period (in vivo):
14 days (observations at 24, 48 and 72 hours and at 4, 7, 10 and 14 days)
Number of animals or in vitro replicates:
Nine
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: Three eyes washed after two seconds, three after four seconds and three eyes not washed.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: 2% fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Unwashed. Corneal bulging with whitish coloured fluid discharge at 14 days.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Grade 2 on Days 7 and 10.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
other: No scores as blanched.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Grade 1 on Day 14.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Unwashed. Grade 4 on Day 14
Irritation parameter:
iris score
Basis:
animal #2
Remarks on result:
other: Because of severe opacity over the rest of the cornea, the iris could not be observed or graded.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks on result:
other: No score as blanched.
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Grade 1 on Day 14
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Remarks on result:
other: Unwashed. Due to severe bulging of the cornea, opacity could not be graded on Days 7 and 10.
Irritation parameter:
iris score
Basis:
animal #3
Remarks on result:
other: Because of severe opacity covering the rest of the cornea, the iris could not be observed or graded.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks on result:
other: No scores as blanched.
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Grade 1 on Day 14.
Irritant / corrosive response data:
Signs of irritation were observed in all eyes from 24 hours through to termination of the study and consisted of moderate to severe opacity, slight to moderate iritis (two eyes could not be observed for iritis throughout the study due to severe opacity), blanching of the conjunctivae, slight to severe chemosis, and slight to moderate discharge. Other signs of irritation included sloughing of the corneal epithelium in seven eyes, sloughing of blanched areas of conjunctivae in three eyes, sluggish pupillary response in eight eyes, alopecia around eye in one eye, bulging of cornea and discharge from cornea in four eyes, and vascularisation of the corneal epithelium in three eyes. The cornea could not be stained with fluorescein at 14 days due to bulging and discharge in four eyes. Positive fluorescein staining on Day 14 revealed corneal damage in five eyes. Only scores for unwashed eyes are presented.
Other effects:
Blinking in all animals, phonation in six animals, and preening in five animals were observed immediately after instillation of the test substance.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In an eye irritation/corrosion study conducted using a protocol similar to OECD TG 405, but not compliant with GLP (reliability score 2) methylsilanetriyl triacetate caused severe, irreversible damage to the eyes of rabbits.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are two reliable skin irritation/corrosion studies available for pure methylsilanetriyl triacetate (Hazleton Laboratories 1990 and Hazleton Laboratories 1970b). The key skin irritation study (Hazelton Laboratories 1990) clearly shows that the substance is corrosive to the skin in a test conducted according to OECD guidelines and in compliance with GLP. A non-guideline study (Hazelton Laboratories, 1970b) showed moderate skin effects which were not reversed at the end of the observation period, including necrosis in one of three animals in which test substance was applied to intact skin. However, the results of this study could not be interpreted in respect of current EU classification criteria for skin irritation/corrosion.

A study was also performed with a preparation containing a mixture of approximately 5% (total) of the registered substance and the related substance triacetoxyethylsilane. (Bayer AG 1986). This preparation is similar to products marketed for professional and consumer sealant applications. Minor, reversible effects were observed but the preparation was not irritant to skin or eyes according to EU classification criteria. 

There are two reliable eye irritation studies on pure methylsilanetriyl triacetate that showed this substance to be corrosive to the eyes of rabbits (Hazelton Laboratories 1970c, BioResearch laboratories Ltd. 1979b). A third study with a preparation containing 5% acetoxysilanes (Bayer AG 1986) resulted in mild, transient irritation to the eyes of rabbits which was entirely reversed after 7 days.

Based on the production of acetic acid following hydrolysis, methylsilanetriyl triacetate is likely to be a respiratory irritant. However, there are no measured data to support this.


Justification for classification or non-classification

On the basis of the available skin irritation/corrosion and eye irritation studies, methylsilanetriyl triacetate is classified 'Skin Corr. 1C' and 'Eye Dam. Cat. 1' with the hazard statement 'H314: Causes severe skin burns and eye damage' according to the criteria of Regulation (EC) No 1272/2008. It is assumed that substances that are corrosive to the skin are also damaging to the eyes, so there is no separate labelling for the eyes. There are no specific data for respiratory irritation.