N-(3-(trimethoxysilyl)propyl)ethylenediamine

Endpoint summary

Description of key information

The key skin irritation study (Dow Corning Corporation, 2000c) found mild irritation to the skin of rabbits, that did not meet the EU criteria for classification. There were no clinical signs of toxicity.  The eye irritation study (Hazelton France, 1993) reported serious damage to rabbit eyes, with effects that were not fully reversed in five of six during the 21-day observation period.

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:

15.10.1998 to 10.02.2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, England
- Age at study initiation: At least 11 weeks
- Weight at study initiation: 2193-2616 g
- Housing: Individually in suspended metal cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-22
- Humidity (%): 44-78
- Air changes (per hr): 18
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20.10.1998 To: 02.11.1998

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

Four hours

Observation period:

Up to 14 days

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: Dorso-lumbar region
- % coverage: 10% approx.
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: Four hours with warm water

SCORING SYSTEM: Draize

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

2.11

Max. score:

8

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 11 days

Remarks on result:

other: Desquamation from Day 7

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 13 days

Remarks on result:

other: Desquamation from Day 4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: Desquamation from Day 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 9 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema

Irritant / corrosive response data:

Well-defined erythema in all three animals and slight edema. Desquamation of the stratum corneum developed in all animals. Dermal reactions resolved completely in all animals by Day 10, 11 or 13.

Other effects:

No deaths or clinical signs of a systemic reaction to treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

In a skin irritation study conducted to EPA OPPTS 870.2500 (Acute Dermal Irritation) and to GLP (reliability score 1) N-(3-(trimethoxysilyl)propyl)ethylenediamine was mildly irritating to the skin of rabbits, but this irritation did not meet the EU criteria for classification. There were no clinical signs of toxicity.

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:

09.09.1992 to 29.01.1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, France
- Age at study initiation: Three months
- Weight at study initiation: 2.5± 0.2 kg
- Housing: Individual in stainless steel cages
- Diet (e.g. ad libitum): 150 g/animal/day
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19± 3
- Humidity (%): Minimum 50%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09.09.1992 To: 29.01.1993

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

Eyes not rinsed

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

Six

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: OECD 405

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Ulceration. Presence of a whitish humour on the side of the lids of the treated eye.

Irritation parameter:

cornea opacity score

Basis:

animal: Animals 2, 3, 4, 5 and 6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Ulceration. Presence of a whitish humour on the side of the lids of the treated eye. Varying areas of neovascularisation of the cornea.

Irritation parameter:

iris score

Basis:

animal: all animals

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Animals 1 reversed between Day 14 and 21, but all others had Grade 1 on Day 21. Circumcorneal injections with/out congestion of the iris. Also some animals had permanent myosis with preservation of the direct photomotor reflex.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Grade 1 on Day 21

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Grade 2 on Day 21

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Grade 2 on Day 21

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Grade 2 on Day 21

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal: 2, 3 and 5

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Grade 1 on Day 21

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Grade 1 on Day 21. Depilation area around the lids of the treated eye.

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Grade 2 on Day 21. Depilation area around the lids of the treated eye.

Irritant / corrosive response data:

Five of the six tested rabbits had effects on the eye that were not reversible in within the 21 day observation period.

Interpretation of results:

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

Conclusions:

In an eye irritation study conducted to OECD 405 and to GLP (reliability score 1) N-(3-(trimethoxysilyl)propyl)ethylenediamine caused serious damage to rabbit eyes, with effects that were not fully reversed in five of six during the 21-day observation period.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are several studies for each of skin and eye irritation. In both cases the supporting data support the findings of the key data.

In a skin irritation study conducted to EPA OPPTS 870.2500 (Acute Dermal Irritation) and to GLP (Dow Corning Corporation, 2000c) N-(3-(trimethoxysilyl)propyl)ethylenediamine was mildly irritating to the skin of rabbits, but this irritation did not meet the EU criteria for classification. Well-defined erythema and slight edema was seen in all three animals, as well as desquamation of the stratum corneum. Dermal reactions resolved completely in all animals by Day 10, 11 or 13. There were no deaths or clinical signs of toxicity.

Four reliable supporting studies for skin irritation were also available, all conducted according to current guidelines and in compliance with GLP. At most mild irritation was evident which was in all cases reversible and did not meet the EU criteria for classification (TNO, 1998, Hüls, 1993, Huntingdon 1993, Hazleton, 1992).

In the key study for eye irritation conducted to OECD 405 and to GLP (Hazleton, 1993) N-(3-(trimethoxysilyl)propyl)ethylenediamine was severely irritating (irreversible) to the eyes of rabbits. Five of the six tested rabbits had serious effects on the eye that were not reversible in within the 21 day observation period. These effects included ulceration and congestion of the cornea and circumcorneal injections.

Several reliable supporting studies for eye irritation were also available, all conducted according to current guidelines and in compliance with GLP. The majority of the studies reported severe, irreversible effects on the eyes of the animals (CIT 1994, Hüls 1993). Corrosive effects reported included a delayed manifestation of a grade 4 corneal lesion lasting until the end of the observation period. Conjunctival blistering was also reported (Toxicogenics Inc., 1981). Irreversible effects in the eyes of rabbits were reported even following washing of the eyes four seconds after treatment (TNO, 1984). Supporting studies which were not reliable or reliability was not assignable are also included in the data set which indicate corrosivity and support the key findings (Industrial Biotest Laboratories 1976, SEHSC 2003). In addition, a reliable pre-GLP eye irritation study which administered the test substance neat caused what was described as minor irritation to the eyes of rabbits (Mellon 1975).

Justification for classification or non-classification

Based on the available information, the registered substance is classified: 'Eye Damage Category 1' with the hazard statement 'H318: Causes serious eye damage' in accordance with the Regulation (EC) No 1272/2008.

The registered substance is not classified for skin irritation according to Regulation (EC) No 1272/2008.