Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The key skin irritation/corrosion study, conducted according to a protocol similar to OECD Test guideline 404 but without information about GLP compliance, found 3-aminopropyl(triethoxy)silane to be corrosive to skin (BRRC, 1990).

The key eye irritation/corrosion study, conducted according to a protocol similar to OECD Test Guideline 405 but without information about GLP compliance, found 3-aminopropyl(triethoxy)silane to be severely irritating with necrosis to the eyes (BRRC, 1989).

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
See below
Principles of method if other than guideline:
No guideline is specified. This study approximates in many respects to OECD 404 including observations for 14 days. The neat material (0.5 ml) was held in occlusive contact for 1 h or 3 min with the shaved skin of 6 rabbits. Insufficient details are given on the purity of the test substance, animals used, test site and animal housing conditions.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no details given
- Age at study initiation: no details given
- Weight at study initiation: no details given
- Housing: no details given
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: no details given

ENVIRONMENTAL CONDITIONS
no details given

IN-LIFE DATES: no details given
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml
- Concentration: neat

Duration of treatment / exposure:
1 h
3 min
Observation period:
14 days
Number of animals:
6 (for each exposure time)
Two animals in the 1-min test were terminated after day 10 for reasons of space.
Details on study design:
TEST SITE
- Area of exposure: not stated
- % coverage: not stated
- Type of wrap if used: gauze covered with loosely held occlusive wrap


REMOVAL OF TEST SUBSTANCE
- Washing: excess removed after exposure
- Time after start of exposure: 1 h; 3 min

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Remarks:
1-hour exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour exposure
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour exposure
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour exposure
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 3 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour exposure
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour exposure
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour exposure
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-min exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-min exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-min exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-min exposure
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-min exposure
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-min exposure
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3-min exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
3-min exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
3-min exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
3-min exposure
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
3-min exposure
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3-min exposure
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
1-h occlusive contact caused well-defined to moderate erythema and slight to moderate oedema in all 6 animals, still present at the 3-day observation but not at 7 days. Necrosis that was full thickness in 2/6 and superficial in 2/6 was evident until observation at day 10, but absent at day 14. Ecchymosis (a hemorrhagic area ) was apparent in 4/6 within 2 h but absent by day 2. Scabbing, desquamation or alopecia were still present in all 4 of the remaining animals at termination on day 14. See table 1.
Exposure for 3 min caused slight to well-defined erythema and very slight to slight oedema in 6/6 that remained in some until day 3 but was not evident on day 7. The only other effect reported was desquamation present in 6/6 at the final 7-day observation. See table 2.

Other effects:
None reported.

Tables from the study report with individual scores for each animal can be found under attachments

Table 1: Exposure for 1 hour

Irritant/corrosive response data (mean for 6 animals) at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema & eschar (mean of 6)

Edema (mean of 6)

Other effects (number of animals with each effect shown)

Max. score: 4

Max. score: 4

2 h

2.3

2.3

2N, 4E

24 h

2.2

2.5

2N+, 2E, 1S

48 h

2.5

2.5

2N+, 1N, 1E, 1S

72 h

2.3

1.5

2N+, 2N, 1D, 1S

Day 7

0.0

0.0

1N+, 2N, 6D, 2S, 3A

Day 10

0.0

0.0

1N+, 6D, 2S, 5A

Day 14 (4 animals)

0.0

0.0

4D, 2S, 4A

Mean 24, 48, 72 h

2.3

2.2

-

Reversibility*

nc

Average time (unit) for reversion

Not fully reversed within 14 days

 

Table 2: Exposure for 3 minutes

Irritant/corrosive response data (mean for 6 animals) at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema & eschar (mean of 6)

Edema (mean of 6)

Other effects (number of animals with each effect shown)

Max. score: 4

Max. score: 4

2 h

1.5

1.0

-

24 h

1.7

1.2

-

48 h

1.5

0.7

1D

72 h

1.2

0.2

1D

Day 7

0.0

0.0

6D

Mean 24, 48, 72 h

1.5

0.7

-

Reversibility*

nc

Average time (unit) for reversion

Not fully reversed within 7 days

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

N+ = full thickness necrosis

N = superficial necrosis

D = desquamation

E = ecchymosis

S = scab formation

A = alopecia

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
A reliable study, conducted in a manner largely similar to OECD 404, found the neat test material to be corrosive when in occluded contact for 1 h, and a minor to moderate irritant when in contact for 3 min. There is no evidence of GLP status in the report, however, Bushy Run Research Center was a certified GLP laboratory during the period of the conduct of this study.
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Remarks:
SIAR (2003) notes that this laboratory was GLP certified at the date of this study
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no details given
- Age at study initiation: : no details given
- Weight at study initiation: no details given
- Housing: no details given
- Diet: standard diet ad libitum
- Water : drinking water ad libitum
- Acclimation period: no details

ENVIRONMENTAL CONDITIONS
no details given

IN-LIFE DATES: no details given
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye usually serves as the control
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml, 0.005 ml
Duration of treatment / exposure:
Eyes unwashed.
Observation period (in vivo):
Observation to 21 days in some cases
Number of animals or in vitro replicates:
6 (3/sex)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: unwashed

SCORING SYSTEM: after Draize, 1959


TOOL USED TO ASSESS SCORE: fluorescein (for 1-day reading)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7.0 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7.0 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.66
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 72 hours and 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
0.1 ml: severe corneal injury, iritis, severe conjunctival irritation and necrosis of the conjunctivae within 1 hour. Because of the severe, possibly irreversible, irritation at 7 days all animals were sacrificed. See table 1.

0.005 ml: minor to severe corneal injury with necrosis of the conjunctivae within 1 hour. Two of six had recovered at 7 days and only 2 showed clear effects at 14 and 21 days. See table 2.

Table 1: Irritant/corrosive response data, mean for 6 animals, dose 0.1 ml

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

Opacity

Max. score: 4

Area involved

Max. score 4

Congestion/swelling

Max. score: 2

Redness

Max. score: 3

Chemosis

Max. score: 4

Discharge

Max. score: 3

1 h

2.7

3.3

*1

2.0

1.7

3.0

4 h

2.8

2.7

*1

2.0

2.0

2.0

24 h

2.5

2.2

1.0

2.2

1.7

3.0

48 h

2.8

2.2

1.0

2.3

1.5

2.8

72 h

3.0

2.5

*1

2.3

1.7

2.7

7 days

3.7

3.7

*

1.5

1.2

1.7

Mean for 24, 48, 72 h

2.8

*

2.3

1.6

Reversibility

Considered possibly irreversible

* scoring not possible for 1 or more animals, mean for the remainder is given

Table 2: Irritant/corrosive response data, mean for 6 animals, dose 0.005 ml (data from selected time intervals are presented here)

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

Opacity

Max. score: 4

Area involved

Max. score 4

Congestion/swelling

Max. score: 2

Redness

Max. score: 3

Chemosis

Max. score: 4

Discharge

Max. score: 3

1 h

1.7

2.2

1.0

2.0

1.3

2.7

24 h

1.5

2.0

1.0

2.0

1.0

2.3

48 h

1.5

2.2

1.0

2.0

1.0

2.0

72 h

1.0

1.8

1.0

1.5

0.7

1.2

7 days

1.2

1.7

0.5

0.7

0

0.7

21 days

0.6

0.6

0

0

0

0

Reversibility

Not fully reversible within 21 days

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
A reliable study, conducted largely according to OECD 405, but not GLP, reported severe eye irritation with necrosis in rabbits. The study was terminated for humane reasons at 7 days, when clear effects were still evident in all six animals.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for skin irritation, conducted according to a protocol similar to OECD Test Guideline 404, but without information about GLP compliance,found the neat test material to be corrosive following occluded contact for 1 hour, and a minor to moderate irritant when in contact for 3 minutes (BRRC, 1990). A supporting study, conducted according to a protocol similar to OECD Test Guideline 404 but not in compliance with GLP, found the neat test material to be corrosive when in occluded contact with skin for 4 hours (BRRC, 1989). Several other reliable supporting studies were also available reporting irritant or corrosive effects, including BRRC (1981), Dow Corning Corporation (1976) and BRRC (1982). Reliability 4 reports (Hazelton Laboratories, 1985, BRRC, 1985) support the data set. Additionally, a non-standard study identified concentration-related dermal irritation following 9 separate 6-hour applications over 11 days. At the lowest concentration of 1 %, irritation was evident (BRRC, 1988). Further supporting evidence for the corrosive or irritation potential of the test substance is provided in a brief review of a limited study that reported moderate necrosis following 24 hours when an unspecified amount of application of the neat material had been applied to the skin of rabbit (Dow Corning Corporation, 1958) as well as in another brief review which used an unstated “short-term” contact with the neat material. Moderate irritation and scarring were observed when repeated and/or prolonged contact had occurred (Dow Corning Corporation, 1976).

 

The key eye irritation study which was conducted according to a standard guideline but without information on GLP compliance, observed that the neat test material was highly irritating to rabbit eyes (BRRC, 1989). Particularly, severe irritation and necrosis were evident, and all animals were sacrificed on day 7 for animal welfare reasons. The supporting studies for eye irritation are in agreement with the key findings (Mellon Institute, 1964, Mellon Institute, 1960, Dow Corning Corporation, 1976, Toxigenics, 1981, Dow Corning Corporation, 1958, Dow Corning Corporation, 1976).

Justification for classification or non-classification

Based on the available data 3-aminopropyl(triethoxy)silane requires classification for skin corrosion Cat 1B and irreversible eye damage Cat 1, H314: "causes severe skin burns and eye damage" according to Regulation (EC) No. 1272/2008.