N-[3-(triethoxysilyl)propyl]ethylenediamine

Endpoint summary

Description of key information

Skin irritation (OECD 404): irritating
Eye irritation (OECD 405): corrosive 

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:

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

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

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system 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: 1.9 kg
- Fasting period before study: no
- Housing: Single housing before and after the exposure period. During exposure the animals were kept singly in restrainers, which allowed free movement of the head but prevented a complete body turn.
- 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

IN-LIFE DATES: From: 17 June 2002 To: 22 Aug 2002

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin site served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 h

Observation period:

14 days; reading time points: 1, 24, 48, and 72 h after patch removal

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: approximately 6 cm²
- Type of wrap if used: Test site covered with a gauze patch, which was held in contact to the skin by means of a semi-occlusive dressing (non-irritating tape).

REMOVAL OF TEST SUBSTANCE
No residual test substance had to be removed.

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

within 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

within 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Erythema grade 1 (2/3 animals) and 2 (1/3 animals) were observed 60 min after patch removal. Very slight oedema reactions (grade 1) were observed in all 3 animals 60 min after removal of the patch but were fully reversible within 24 h (2/3) and 72 h (1/3), respectively. Skin induration was observed in all 3 animals from day 4 until the end of the study. A dark brown discoloured application area was observed in one animal from 4 days to the end of the study. Peeling of the application site was observed in 3/3 animals after 9 days and persisted until the end of the study. Laceration of skin induration was observed in 1/3 animals at day 6, 7, and 9.

Table 1: Individual results of the skin irritation test.

Rabbit No.	1		2		3
Observation time	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	2	1	1	1	1	1
24 h	2	1	1	0	1	0
48 h	2	1	1	0	1	0
72 h	2	0	1	0	1	0
14 d	2 a,b,c	0	1 a,c	0	1 a,c	0
Mean value	2	0.66	1	0	1	0
24 + 48 + 72 h

a: skin induration

b: application site dark brown discoloured

c: peeling of the application site

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

A reliable study performed in accordance with OECD 404 and GLP found the test material to be irritating to the skin of rabbits. Erythema grade 1 (2/3 animals) and 2 (1/3 animals) were observed 60 min after patch removal. Very slight oedema reactions (grade 1) were observed in all 3 animals 60 min after removal of the patch but were fully reversible within 24 h (2/3) and 72 h (1/3), respectively. Skin induration was observed in all 3 animals from day 4 until the end of the study. A dark brown discoloured application area was observed in one animal from 4 days to the end of the study. Peeling of the application site was observed in 3/3 animals after 9 days and persisted until the end of the study. Laceration of skin induration was observed in 1/3 animals at day 6, 7, and 9. No systemic effects were reported.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

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.

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

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

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.

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

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

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

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 9 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 9 days

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).

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.

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)

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A skin irritation test is available with N-[3-(triethoxysilyl)propyl]ethylenediamine (CAS 5089-72-5), which was performed in Himalayan rabbits according to OECD 404 and in compliance with GLP (LPT, 2002a). Pure test substance (0.5 ml) was applied to a 6 cm² application site (shaved) for 4 h under semi-occlusive conditions. No residual test substance had to be removed. Sixty minutes and 24, 48, 72 h after patch removal the application site was examined. Erythema grade 1 (2/3 animals) and 2 (1/3 animals) were observed 60 min after patch removal. Very slight edema reactions (grade 1) were observed in all 3 animals 60 min after removal of the patch but were fully reversible within 24 h (2/3) and 72 h (1/3), respectively. Skin induration was observed in all 3 animals from day 4 until the end of the study. A dark brown discoloured application area was observed in one animal from 4 days to the end of the study. Peeling of the application site was observed in 3/3 animals after 9 days and persisted until the end of the study. Laceration of skin induration was observed in 1/3 animals at day 6, 7, and 9. No systemic effects were reported. In summary, the mean erythema scores over 24, 48, and 72 h were 2, 1, and 1 for animals #1 -3, and the mean edema scores over 24, 48, and 72 h were 0.66, 0, and 0 for animals #1 -3, respectively. Thus, N-[3-(triethoxysilyl)propyl]ethylenediamine is concluded to be irritating to the skin under the conditions of the test.

 

Eye irritation

An eye irritation test is available with N-[3-(triethoxysilyl)propyl]ethylenediamine (CAS 5089-72-5), which was performed in Himalayan rabbits according to OECD 405 and in compliance with GLP (LPT, 2002b). Pure test substance (0.1 ml) 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. 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 edematous cornea 14 to 17 days after instillation. 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. In conclusion, N-[3-(triethoxysilyl)propyl]ethylenediamine was corrosive to the eye under the conditions of the test

Justification for classification or non-classification

The available data on skin irritation/corrosion of the test substance meet the criteria for classification as Category 2 (Causes skin irritation (H315)) according to Regulation (EC) No. 1272/2008.. Basis for the classification was the fact that inflammation, indicated by the occurrence of erythema (grade 1+2), induration, and peeling of the skin, were observed in all 3 animals at the end of the 14-day observation period.

 

The available data on eye irritation of the test substance meet the criteria for classification as Category 1 (Causes serious eye damage (H318)) according to Regulation (EC) Np. 1272/2008. Basis for the classification was the fact that effects on cornea (grade 2) and iris (grade 1) were observed in all 3 animals at the end of the 21-day observation period.