N-[3-(triethoxysilyl)propyl]ethylenediamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 May - 4 July 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(adopted 1987)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Freie und Hansestadt Hamburg, Behörde für Arbeit, Gesundheit uns Soziales, Hamburg, Germany

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(triethoxysilyl)propyl]ethylenediamine

EC Number:

225-806-1

EC Name:

N-[3-(triethoxysilyl)propyl]ethylenediamine

Cas Number:

5089-72-5

Molecular formula:

C11H28N2O3Si

IUPAC Name:

N-[3-(triethoxysilyl)propyl]ethylenediamine

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: LPT, Laboratory of Pharmacology and Toxicology KG, Loehndorf, Germany
- Age at study initiation: approximately 4 months
- Weight at study initiation: 2.1 kg
- Fasting period before study: no
- Housing: Single housing before and after the exposure period. For 8 h following the test substance application the animals were kept singly in restrainers, which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eye by excrements and urine.
- Diet: ssniff K-H (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 55± 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated left eye served as control

Amount / concentration applied:

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

Duration of treatment / exposure:

single application without rinsing

Observation period (in vivo):

21 days; reading time points: 1, 24, 48, and 72 h after administration

Number of animals or in vitro replicates:

3 males

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

The test substance was placed in the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, and 72 hours after the administration. 24 h after administration the eyes were treated additionally with fluorescein and examined.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 21 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 9 days

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 9 days

Results 7

Irritation parameter:

iris score

Basis:

other: mean out of all animals

Time point:

24/48/72 h

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: Evaluation not possible (no justification given in the study report).

Results 8

Irritation parameter:

chemosis score

Basis:

other: mean out of all 3 animals

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritant / corrosive response data:

Corneal opacity was observed at 1 h in all 3 animals (grade 1: 2/3; grade 2: 1/3). Opacity increased after 24 and 48 h (grade 3: 2/3; grade 2: 1/3). From 72 h until 21 days opacity (grade 2) was observed in all animals. Iris evaluation was not possible at 24 and 48 h in all animals. At 72 h iris scores of 1 and 2 were observed in one animal each (no evaluation possible in the third animal). From day 4 until day 21 the iris scores persisted (grade 1) in all animals. Redness was observed after 1 h and was fully reversible within 8 and 9 days, respectively. Chemosis was observed after 1 h (grade 3) and was fully reversible within 6 days. In addition, hair loss around the eyes was observed in 2 animals from 24 h until day 11 and in one animal from 48 h until day 12. White deposits, (probably pus) in the conjunctival sac were observed in 2/3 animals 72 h to 6 days after instillation, and in 1/3 animals from 24 h to 8 days after instillation. Enlargement of the bulbus due to accumulation of fluid below the cornea was noted in 2/3 animals from day 8 to 21 and in 1/3 animals from day 7 to 21. 1/3 animals showed oedematous cornea 14 to 17 days after instillation.

Other effects:

No systemic intolerance reactions were observed.

Any other information on results incl. tables

Table 1: Individual results of the eye irritation study in rabbits.

Rabbit #	Time	Conjunctivae		Iris	Cornea
		Redness	Swelling
1	1 h	0	3	0	1
	24 h	1	2	-	2
	48 h	1	1	-	2
	72 h	1	1	-	2
	21 days	0	0	1	2
	mean (24, 48, 72 h)	1	1.33		2
2	1 h	0	3	0	1
	24 h	1	2	-	3
	48 h	1	1	-	3
	72 h	1	1	1	2
	21 days	0	0	1	2
	mean (24, 48, 72 h)	1	1.33		2.66
3	1 h	0	3	0	2
	24 h	1	2	-	3
	48 h	1	1	-	3
	72 h	1	1	2	2
	21 days	0	0	0	2
	mean (24, 48, 72 h)	1	1.33		2.66

-: no evaluation possible (no justification given in the study report)

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

A reliable study performed in accordance with OECD 405 and GLP found the test material to be corrosive to the eye of rabbits. Mean values (over 24, 48, 72 h) for cornea score were 2, 2.66, and 2.66 in animal 1, 2, and 3, respectively. Mean values for redness (over 24, 48, 72 h) was 1 in all animals. Mean values (over 24, 48, 72 h) for chemosis score were 1.33 in all animals. Iris evaluation was not possible up to 48 in all animals. Effects on cornea (grade 2) and iris (grade 1) were not reversible within 21 days.