3-(trimethoxysilyl)propylamine

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

3-aminopropyltriethoxysilane

EC Number:

213-048-4

EC Name:

3-aminopropyltriethoxysilane

Cas Number:

919-30-2

Molecular formula:

C9H23NO3Si

IUPAC Name:

3-triethoxysilylpropan-1-amine

Test animals / tissue source

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

Test system

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)

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

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

Results 13

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

Results 14

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

Results 15

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

Results 16

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

Results 17

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

Results 18

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

Results 19

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

Results 20

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

Results 21

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

Results 22

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

Results 23

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

Results 24

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 conjuctival irritation and necrosis of the conjunctivae within 1 h. 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 h. Two of six had recovered at 7 days and only 2 showed clear effects at 14 and 21 days. See table 2.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.