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Description of key information

In the key skin irritation study, conducted according to EPA OPP81-5 Test Guideline (similar to OECD Test Guideline 404) and in compliance with GLP, (3-chloropropyl)triethoxysilane (CAS 5089-70-3; EC 225-805-6) did not cause significant irritation and was not corrosive to the rabbit skin (WIL Research Laboratories Inc. 1996c).

In the key eye irritation study, conducted according to OECD Test Guideline 405 and in compliance with GLP, (3-chloropropyl)triethoxysilane was not irritating to the rabbit eyes (Dow Corning Corporation 1995d).

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:
1995-09-26 to 1995-10-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver, PA
- Age at study initiation: Young adult, age not specified
- Weight at study initiation: 2313 to 2463 g
- Housing: Individual suspended wire-mesh cages
- Diet: Purina Certified Rabbit Chow, ad libitum
- Water municipal water, ad libitum
- Acclimation period: minimum 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 67.5 - 68.6°F (19.4 - 20°C)
- Humidity: 38.4-45.8 %
- Air changes (per hr): not specified
- Photoperiod: 12 hours dark/ 12 hours light

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:
until no abnormal observations at 11 days
Number of animals:
6 (2 males and 4 females)
Details on study design:
TEST SITE
- Area of exposure: 1x1 dorsal skin removed from hair
- % coverage: one inch square
- Type of wrap if used: 2-ply gauze path overwrapped with a gauze binder and se cured with Dermiform tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with disposable paper towels moistened with deionized water
- Time after start of exposure: at the end of 4 hours

OBSERVATION TIME POINTS
The animals were observed for mortality twice daily (morning and afternoon) for the duration of the study. The applications sites were observed for erythema, oedema, and other dermal findings approximately 30-60 minutes and 24,48 and 72 hours after patch removal and through day 11 if irritation persisted.
Body weights were obtained and recorded on study day 0 (initiation) and at each animal's termination from the study.
Upon termination from the study, the rabbits were euthanized by intravenous injection of sodium pentobarbital solution and discarded.

SCORING SYSTEM:
- Method of calculation: method of Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 1, 24, 48, 72 h
Score:
0.4
Max. score:
8
Reversibility:
fully reversible within: 11 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
19703
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
probability of weak irritation
Remarks:
very slight erythema
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
19707
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
probability of weak irritation
Remarks:
very slight erythema
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
19722
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
Remarks:
19726
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
probability of weak irritation
Remarks:
very slight erythema
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
19731
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
19732
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
Remarks:
19703
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
Remarks:
19707
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
Remarks:
19722
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
Remarks:
19726
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
19731
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
19732
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test material induced very slight erythema (grade 1) in three of six animals at 24, 48 or 72 hours, and desquamation in all animals from 72 hours. There was no oedema or other dermal findings. All irritation was reversible; erythema and desquamation were no longer evident at day 6 and day 11, respectively. The Primary Irritation Index (mean at 1, 24, 48 and 72 h) was calculated to be 0.4. The test material was described as slightly irritating.
Other effects:
There were no deaths or remarkable body weight changes during the study period.
Interpretation of results:
GHS criteria not met
Conclusions:
In a skin irritation study, conducted according to EPA OPP81-5 Test Guideline (similar to OECD Test Guideline 404) and in compliance with GLP, (3-chloropropyl)triethoxysilane did not cause significant irritation and was not corrosive to the rabbit 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:
1995-01-06 to 1995-02-03
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: Hazleton Research Products, Inc., Kalamazoo, Michigan
- Age at study initiation: ca. 4 months
- Weight at study initiation: 2661-2851g
- Housing: Individual hanging stainless steel wire mesh cages
- Diet: 125g/day, Certified Rabbit Chow #5322 (Purina Mills, Inc., Louis, Missouri)
- Water: ad libitum
- Acclimation period: 32 days

ENVIRONMENTAL CONDITIONS

- Temperature (°F): 67-69 (19.4-20.6 °C)
- Humidity (%): 54
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 30/12/1994 To: 03/02/1995
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated eye.
Amount / concentration applied:
TEST MATERIAL

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



Duration of treatment / exposure:
Single instillation, not rinsed.
Observation period (in vivo):
Eye examinations were carried out at 1, 24, 48 and 72 hours after dosing.
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): not rinsed

SCORING SYSTEM: According to guideline.

TOOL USED TO ASSESS SCORE: hand-slit lamp, fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
All three animals exhibited moderate redness and slight to very slight chemosis of the conjunctivae at the one-hour observation period. This conjunctival irritation cleared by the 24-hour observation period. The primary eye irritation score is 0.
Other effects:
No deaths or overt signs of toxicity were observed during the study.

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 

2/2/2 

2/1/1 

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

Reversibility*

 -

Average time (unit) for reversion

 -

By 24 hours 

 By 24 hours

 

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

 

Interpretation of results:
GHS criteria not met
Conclusions:
In an eye irritation study conducted according to OECD Test Guideline 405 and in compliance with GLP, (3-chloropropyl)triethoxysilane was not irritating to the rabbit eyes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the case of skin irritation, the most recent of the most reliable studies was selected as the key study.

In the key skin irritation study, conducted according to EPA OPP81-5 Test Guideline (similar to OECD Test Guideline 404) and in compliance with GLP, 0.5 mL doses of (3-chloropropyl)triethoxysilane were applied to the shaved, intact skin of six albino rabbits under semi-occlusive dressings for a 4-hour exposure period. Application sites were evaluated in accordance with the method of Draize at approximately 30-60 minutes and 24, 48, 72 hours after patch removal and through day 11 if irritation persisted. The test material induced very slight erythema and desquamation on five of six animals. There were no oedema or other dermal findings. All signs of irritation had reversed and completely subsided by day 11 or earlier. Overall, the conclusion was that the test substance did not cause significant irritation for classification (WIL Research Laboratories Inc. 1996c).

In a supporting study conducted according to OECD Test Guideline 404 and in compliance with GLP, 0.5 mL of (3-chloropropyl)triethoxysilane was uniformly applied to an intact skin site of three female rabbits. The test areas were covered in a semi-occlusive fashion for a period of four hours and evaluated for dermal irritation approximately at 30-60 minutes and 24, 48 and 72 hours after bandage removal using the Draize method. No signs of illness and no skin irritation were observed in any of the rabbits. It was concluded that (3-chloropropyl)triethoxysilane is not an irritant to the skin of rabbits, under the conditions of this test (Dow Corning Corporation 1995c).

Four other older and less reliable studies are also available. Three of them found the test substance to be slightly irritant to the skin of New Zealand White rabbits (TNO-CIVO 1980; Consultox Laboratories 1976b; Laboratorium Für Pharmakologie und Toxikologie 1977). Although the studies cannot be used for classification as mean erythema and oedema scores at 24/48/72 time points were not determinable, based on the available information, it is unlikely that the substance would meet the EU criteria for classification as a skin irritant.

The other study found the test substance not irritating to the skin of New Zealand White male and female rabbits (Laboratorium Für Pharmakologie und Toxikologie 1976). These four supporting studies were conducted prior to the adoption of Test Guidelines and GLP but were meeting generally accepted scientific principles.

In the key eye irritation study conducted according to OECD Test Guideline 405 and in compliance with GLP, 0.1 mL of (3-chloropropyl)triethoxysilane was instilled into the eyes of three male rabbits. The eyes remained unwashed. The cornea, iris, conjunctivae and chemosis readings for all animals were carried out at 1, 24, 48 and 72 hours after dosing. All three animals exhibited moderate redness and slight to very slight chemosis of the conjunctivae at the one-hour observation period. This conjunctival irritation cleared by the 24-hour observation period. Therefore, the test substance was concluded non-irritant to the eyes of rabbits (Dow Corning Corporation 1995d).

In a supporting eye irritation study, conducted according to EPA OPP81-4 Test Guideline (similar to OECD Test Guideline 405) and in compliance with GLP, 0.1 mL of (3-chloropropyl)triethoxysilane was instilled into the lower sac of the right eye of six albino rats. The eyelids were held closed for approximately one second and released. Left eyes were manipulated in a similar manner to the right eyes and served as controls. The eyes of all rabbits remained unwashed. The eyes were examined for ocular reactions in accordance with the method of Draize at approximately one, 24, 48 and 72 hours after dosing and on days 4 and 7 if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at 72 hours and on day 7. An iridal reaction was noted in the treated eye of one animal. Minor conjunctival irritation was noted for all rabbits. There were no corneal findings. All irritation was reversible and completely subsided by day 7 or earlier. Therefore, the test substance was concluded non-irritant to the eyes of rabbits (WIL Research Laboratories Inc. 1996d).

Three other older and less reliable studies are also available. There were all conducted prior to the adoption of Test Guidelines and GLP but are meeting generally accepted scientific principles and support the above findings (TNO-CIVO 1980; Laboratorium Fur Pharmakologie und Toxicologie 1977; Consultox Laboratories 1976c).

Justification for classification or non-classification

Based on reliable in vivo skin and eye irritation data, (3-chloropropyl)triethoxysilane does not require classification for skin and eye irritation according to Regulation (EC) No 1272/2008.