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Description of key information

Skin irritation (OECD TG 404): Irritating 
Eye irritation (OCED TG 405): Irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11-02-1994 to 22-03-1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to the appropriate OECD test guideline and in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Not reported.
- Age at study initiation: Young adult.
- Weight at study initiation: 3235 - 3389 g
- Housing: Individual suspended wire-mesh cages.
- Diet: Purina® Certified Rodent Chow® #5322 provided ad libitum
- Water: Municipal water were provided ad libitum
- Acclimation period: The animals were acclimated to laboratory conditions for a minimum of six days prior to initiation of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature : 66-70°F
- Humidity (%): 32-70
- Photoperiod (hrs dark / hrs light): 12/ 12.

IN-LIFE DATES: From: 08-04-1994 To: 22-04-1994.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:
4 h
Observation period:
14 days
Reading time points: 30-60 min, 24, 48, 72 h and daily to day 14.
Number of animals:
1 male and 2 females
Details on study design:
TEST SITE
- Area of exposure: One inch square patch on the back of the rabbit.
- % coverage: 20-25 %
- Type of wrap if used: Each 0.5 ml dose was applied under a 2-ply, one inch square gauze patch secured in place with surgical porous tape, that was overwrapped with a gauze binder and secured with Dermiform® tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The site was wiped with disposable paper towels moistened with deionised water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 d. Although very slight erythema persisted through study termination for a single animal this irritation was considered to be reversible.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Other effects:
The test material induced moderate to slight erythema on two and one rabbits, respectively. All rabbits had very slight edema. Desquamation was noted for all rabbits by Day 5. Dermal irritation subsided by Day 14 for one animal. Desquamation persisted through Day 14 for two rabbits. Very slight erythema was present on Day 14 for one animal. There were no other dermal findings.

Table 1. Results of skin irritation study

Observation time

Rabbit no.

1

2

3

E*

O*

E

O

E

O

1 h

2

1

2

1

2

1

24 h

2

1

2

1

2

1

48 h

3

1

3

0

2

1

72 h

3

1

3

0

2

1

Mean value
24 +48 + 72 h

2.67

1.00

2.67

0.33

2.00

1.00

Mean value
24 +48 + 72 h,
all animals

2.44

0.77

 

 

 

 

 

* E: erythema, O: oedema (according to Draize Score)

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal irritation/corrosion study conducted according to OECD 404 and GLP, the primary irritation index was calculated to be 3.1. The test material, triethoxysilane produced moderate, reversible dermal irritation under the conditions of this study and therefore classified as a Category II skin irritant (EU).
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The study did not meet current guideline requirements for acute dermal irritation/corrosion. It does, however, add weight of evidence for acute dermal irritation/corrosion potential.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was applied in 0.01 ml amounts to clipped, uncovered intact skin of 5 rabbit bellies either undiluted or in progressive dilutions of 10, 1, 0.1, and 0.01 % in solvent. Ten grades were recognised based on appearance of moderate or marked capillary injection, erythema, edema or necrosis within 24 hours. No injury from undiluted = grade 1.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
- Diet: Wayne diets ad libitum except during period of manipulation or confinement.
- Water: Water ad libitum except during period of manipulation or confinement.
Type of coverage:
open
Preparation of test site:
shaved
Vehicle:
other: Undiluted or in solvent
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.01 ml
- Concentration (if solution): The substance was applied either undiluted or in progressive dilutions of 10, 1, 0.1, and 0.01 % in solvent.

Duration of treatment / exposure:
No data
Observation period:
No data
Number of animals:
5
Details on study design:
TEST SITE
- Area of exposure: Uncovered intact skin of rabbit bellies.
Irritation parameter:
other:
Remarks on result:
other: No irritation on 2 of 5 rabbits, moderate capillary injection on one, marked capillary injection on 2. Grade 2.
Other effects:
No irritation on 2 of 5 rabbits, moderate capillary injection on one, marked capillary injection on 2. Grade 2.
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Administration of small amount of the undiluted material resulted in trace irritation to uncovered rabbit skin.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The study did not meet current guideline requirements for acute eye irritation/corrosion. It does, however, add weight of evidence for acute eye irritation/corrosion potential.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Single instillation of 0.005, 0.02, 0.10 or 0.5 ml undiluted or of 0.5 mL of 40, 15, 5 and 1 % dilution of the test substance were made into conjunctival sac of 5 rabbits. Read immediately unstained and after fluorescein at 24 hours, with ten grades recognised. Trace or no injury from 0.5 ml undiluted – Grade 1.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Diet: Wayne diets ad libitum except during period of manipulation or confinement.
- Water: Water ad libitum except during period of manipulation or confinement.
Vehicle:
other: Dimethyl phthalate (DMP).
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5, 0.10, 0.02, 0.005 mL (undiluted). 0.5 ml (diluted)
- Concentration (if solution): 40, 15, 5 and 1% dilution

Duration of treatment / exposure:
24 h
Observation period (in vivo):
Not reported
Number of animals or in vitro replicates:
5
Details on study design:
TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
other:
Remarks on result:
other: Severe corneal injury, with iritis, from 0.005 ml undiluted per eye and from 0.5 ml per eye of a 1% dilution in DMP; minor corneal injury on 5 eyes from a 5% dilution in DMP.
Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Severe corneal injury, with iritis, from 0.005 ml undiluted per eye and from 0.5 ml per eye of a 1% dilution in DMP; minor corneal injury on 5 eyes from a 5% dilution in DMP.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11-02-1994 to 22-03-1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to the appropriate OECD test guideline and in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Not reported.
- Age at study initiation: Young adult.
- Weight at study initiation: 2122 - 2285 g
- Housing: Individual suspended mesh-bottom cages.
- Diet: Purina® Certified Rodent Chow® #5322 provided ad libitum
- Water: Municipal water were provided ad libitum
- Acclimation period: The animals were acclimated to laboratory conditions for a minimum of six days prior to initiation of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature : 66-72°F
- Humidity (%): 34-80
- Photoperiod (hrs dark / hrs light): 12/ 12.

IN-LIFE DATES: From: 18-04-1994 To: 24-05-1994.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
Group 1- Single exposure, without washing.
Group 2 - Single exposure, with washing after 30 seconds.
Observation period (in vivo):
1, 24, 48 and 72 hours after dosing and on days 4, 7, 14, 21 and 28.
Number of animals or in vitro replicates:
4 male and 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The rabbits in group 2 were given a washout 30 sec after instillation with 100 ml of sterile saline over a period of 20 seconds. The eyes of the animals in group 1 remained unwashed.
- Time after start of exposure: Approximately 30 seconds following administration of the dose.


TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 28 days
Remarks on result:
other: Corneal opacity persisted through Day 28 (study termination).
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 28 days
Remarks on result:
other: Minor conjuctival redness persisted through Day 28 (study termination).
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
4
Max. score:
2
Reversibility:
fully reversible within: 28 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
The test material induced generally moderate ocular irritation including positive corneal and conjunctival irritation in the right eye of all animals and positive iridal reactions for three and two, unwashed and washed rabbits, respectively. Iridal irritation completely subsided by day 14 or earlier for the unwashed group and by day 4 for the washed group. Corneal irritation completely subsided by day 21 or earlier for all washed animals and by day 14 or earlier for two of the unwashed animals. Minor, reversible conjunctival redness persisted through day 21 for one washed eye. Corneal opacity and minor conjunctival redness persisted through day 28 (study termination) for one unwashed animal.

 Table 1. Ocular Irritation

Group

No. with ocular reactions/ No. treated

Cornea

Iris

Conjunctiva

Total

0.1 ml/ right eye, unwashed

3/3

3/3

3/3

3/3

0.1 ml/ right eye, washed

3/3

2/3

3/3

3/3
Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A reliable eye irritation study, conducted according to OECD 405 and GLP, showed the test material to be a Category 1 eye irritant (EU).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment. Other available data are included as supporting studies.

A key skin irritation study, conducted in compliance with GLP and according to OECD TG 404, showed that triethoxysilane induced moderate to slight erythema on two and one rabbits, respectively. All rabbits had very slight oedema. Desquamation was present in all rabbits by day 5. Dermal irritation subsided by day 14 in one animal. Desquamation persisted through day 14 in two rabbits. Very slight erythema was present on day 14 in one animal. The primary irritation index was calculated to be 3.1. Triethoxysilane produced moderate dermal irritation under the conditions of this study and very slight erythema which persisted until termination in a single animal (DCC, 1995d).

A limited report on skin irritation was also available, which was not conducted according to guideline or in compliance with GLP (reliability score 4). The application of the undiluted test material on rabbit skin resulted in trace irritation (Wacker, 1978). Furthermore, in the previously discussed acute dermal toxicity study with triethoxysilane, severe erythema, moderate to severe edema, fissuring, eschar and exfoliation was observed in all animals. In addition, six rabbits had evident corrosive dermal effects, in addition to a single occurrence of blanching. Desquamation was present on all animals by day 5 and persisted throughout the remainder of the study. There were no other dermal findings. Severe erythema and slight to moderate edema persisted until study termination (day 14) in four rabbits. Erythema was reduced to slight and very slight for five and one animal, respectively, and edema had decreased to slight or very slight for nine rabbits by study termination (DCC, 1995c). The results of all three studies are in agreement and give evidence for the skin irritation potential of triethoxysilane.

The key study for eye irritation which was conducted in compliance with GLP and according to OECD TG 405, showed that triethoxysilane induced moderate ocular irritation and corneal and conjunctival irritation in the right eye of all animals and positive iridal reactions for three and two, unwashed and washed rabbits respectively. Iridial irritation had completely subsided by day 14 or earlier for the unwashed group and by day 4 for the washed group. Corneal irritation completely subsided by day 21 or earlier for all washed animals and by day 14 or earlier for two of the unwashed animals. Minor, reversible conjunctival redness persisted through day 21 for one washed eye. Corneal opacity and minor conjunctival redness persisted through day 28 (study termination) for one unwashed animal (DCC, 1995e). Furthermore, a limited report of an eye irritation study without guideline or GLP compliance (reliability score 4) on triethoxysilane, reported severe corneal injury, with iritis, from 0.005 ml undiluted per eye and from 0.5 ml per eye of a 15 % dilution in dimethyl phthalate (DMP); minor corneal injury on 5 eyes from a 5 % dilution in DMP (Wacker, 1978). The results of both experiments are in agreement and give evidence for an eye irritation potential of triethoxysilane.


Justification for selection of skin irritation / corrosion endpoint:
The key study was selected for assessment.

Justification for selection of eye irritation endpoint:
The key study was selected for assessment.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the available study for skin irritation, triethoxysilane needs to be classified as R38 ‘’Irritating to skin’’ according to the criteria of EU Directive 67/548/EEC, and Skin Irritant Category 2 under Regulation 1272/2008.

Based on the available study for eye irritation, triethoxysilane needs to be classified as R41 ‘’Risk of serious damage to eyes’’ according to the criteria of EU Directive 67/548/EEC, and Eye Irritant Category 1 under Regulation 1272/2008.