Triethoxy(3-isocyanatopropyl)silane

Endpoint summary

Description of key information

In the key skin irritation study, conducted according to OECD Test Guideline 404 and in compliance with GLP, triethoxy(3-isocyanatopropyl)silane was concluded to be corrosive to skin (Bushy Run Research Center, 1994).

In the key eye irritation study, which pre-dated GLP but was conducted according to a guideline similar to OECD Test Guideline 405, triethoxy(3-isocyanatopropyl)silane was concluded to be irritating to eyes (Chem Hygeine Fellowship, 1973e).

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:

19 August 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The restrictions were (i) scoring of animals not provided (ii) occlusive patch used (semi-occlusive recommended).

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(scoring of animals not provided; occlusive patch used (semi-occlusive recommended))

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (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: HRP, Inc., Denver, PA
- Age at study initiation: ~ 13 to 18 weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: no data available
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 61 to 70 °F [16-21 °C]
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: ~ 1 April 1994 To: 6 May 1994

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

3 minutes or 1 hour

Observation period:

14 days (reading at 1, 24, 48 and 72 hours, and at 7 and 14 days)

Number of animals:

1/sex given 1-hour treatment
3/sex given 3-minute treatment

Details on study design:

TEST SITE
- Area of exposure: 1-inch square (~6 cm2)
- % coverage: no data available
- Type of wrap if used: gauze patch secured by adhesive tape, and polyethylene sheet around trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not performed

SCORING SYSTEM:
As per OECD guideline 404

Irritation parameter:

erythema score

Remarks:

1-hour exposure period

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Remarks:

1-hour exposure period

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.6

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

1-hour exposure period

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Remarks:

3-minute exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Remarks:

3-minute exposure

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Remarks:

3-minute exposure

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Remarks:

3-minute exposure

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.6

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Remarks:

3-minute exposure

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Remarks:

3-minute exposure

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

3-minute exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

3-minute exposure

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.6

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

3-minute exposure

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

3-minute exposure

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

3-minute exposure

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.6

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

3-minute exposure

Basis:

animal #6

Time point:

24/48/72 h

Score:

3.6

Max. score:

4

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

After three minutes of contact, severe oedema was seen in all rabbits 1 to 24 hours after exposure. Moderate to severe oedema was observed between 1 and 48 hours. Two rabbits developed superficial necrosis by one hour, and the remaining developed superficial necrosis by day 14. All rabbits developed ecchymoses by 72 hours, which subsided by day 14. All rabbits had desquamation and 5/6 had alopecia by day 14. Also observed were tan discolouration (3/6 rabbits by day 7), fissures (4/6 rabbits by day 14) and scab formation (1 rabbit at day 14).

After one hour of contact, severe oedema with moderate erythema was seen in both rabbits within the first hour of exposure. Erythema was severe within 48 hours. Ecchymoses were observed in both rabbits at 24 and 48 hours. Superficial necrosis and fissures were apparent on both rabbits by day 7. By day 9, superficial necrosis progressed to full thickness necrosis on the female rabbit. Necrosis persisted for 14 days in both rabbits. Desquamation, scabs and alopecia were observed on each animal on day 14.

The test material was clearly corrosive based on the description given.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

In a GLP study performed according to OECD Test Guideline 404, undiluted triethoxy(3-isocyanatopropyl)silane was corrosive to the skin of rabbits when applied for one hour.

Executive summary:

In an acute dermal irritation/corrosion study carried out to GLP and according to OECD Test Guideline 404, rabbits were exposed dermally to triethoxy(3-isocyanatopropyl)silane.

0.5 ml undiluted triethoxy(3-isocyanatopropyl)silane was applied under occlusion to the clipped, intact skin of groups of rabbits for three minutes (3 animals/sex) or for one hour (1 animal/sex). Animals were then observed at 1, 24, 48 and 72 hours, and at 7 and 14 days.

Moderate to severe irritation were seen after 1-48 hours in all rabbits given three-minute applications. Superficial necrosis was seen in two animals after 2 hours and in all six by 14 days; it did not develop to full thickness necrosis. Other effects included alopecia, tan discolouration, fissures and scab formation. Hour-long treatments resulted in severe irritation, including severe erythema and ecchymoses [haemorrhagic spots], in both animals by 48 hours. Superficial necrosis and fissures were present in both rabbits by day 7 and developed to full thickness necrosis in one rabbit by 14 days. Desquamation, scabs and alopecia were seen in both animals at 14 days.

Under these experimental conditions, undiluted triethoxy(3-isocyanatopropyl)silane was corrosive to the skin of rabbits when applied for one hour.

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

Study period:

No data.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(different grading system, eyes examined at 0 and 24 hours (not at 1, 24, 48, and 72 hours), not checked for reversibility (at 7, 14 and 21 days), insufficient data to further judge compliance with test guideline)

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: no data available
- Age at study initiation: no data available
- Weight at study initiation: no data available
- Housing: no data available
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data available
- Humidity (%): no data available
- Air changes (per hr): no data available
- Photoperiod (hrs dark / hrs light): no data available

IN-LIFE DATES: no data available

Vehicle:

other: propylene glycol

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.005, 0.02, 0.1 or 0.5 ml (undiluted) or 0.5 ml (diluted)
- Concentration (if solution): 1, 5, 15, 40 or 100%

VEHICLE
- Amount(s) applied (volume or weight with unit): no data available
- Concentration (if solution): no data available
- Lot/batch no. (if required): no data available
- Purity: no data available

Duration of treatment / exposure:

24 h

Observation period (in vivo):

24 h

Number of animals or in vitro replicates:

5/dose group

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not performed

SCORING SYSTEM: graded from 1 to 10 (trace or no injury from 0.5 ml undiluted = grade 1)

TOOL USED TO ASSESS SCORE: unstained, and stained with fluorescein

Irritation parameter:

overall irritation score

Basis:

other: no data available

Time point:

other: 0 or 24 h

Score:

9

Max. score:

10

Reversibility:

other: reversibility not assessed

Remarks on result:

other: Severe corneal damage and iritis in response to 0.005 ml undiluted or to 0.5 ml of 5% or 15%; moderate eye injury in response to [presumably] 1%

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: individual animal scores were not given in the study report.

Irritant / corrosive response data:

Severe corneal damage and iritis following instillation of 0.005 ml undiluted test substance, or 0.5 ml of a 5% or 15 % solution (in propylene glycol). Application of 0.5 ml of [presumably] 1 % produced moderate eye irritation. [The summary report is ambiguous and actually states: "moderate eye injury from 1% PG solution."

Other effects:

No data available

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In a non-guideline study described by two summary reports, triethoxy(3-isocyanatopropyl)silane was severely irritating to the eyes of rabbits.

Executive summary:

Two summary reports describe an eye irritation study, similar to OECD Test Guideline 405, in rabbits exposed to triethoxy(3-isocyanatopropyl)silane.

Triethoxy(3-isocyanatopropyl)silane was applied undiluted (at 0.005, 0.02, 0.1 or 0.5 ml), or in propylene glycol (0.5 ml at 1, 5, 15 or 40%) to the eyes of groups of five rabbits. Observations were made immediately after treatment (without staining) and after 24 hours (stained with fluorescein).

An undiluted administration of 0.005 ml triethoxy(3-isocyanatopropyl)silane caused severe corneal damage and iritis, as did 5% and 15% solutions. Moderate eye injury was observed following treatment with the 1% solution. An overall eye irritation grade of 9 was allocated to triethoxy(3-isocyanatopropyl)silane (on a scale of 1 (trace or no injury from 0.5 ml undiluted) to 10).

Triethoxy(3-isocyanatopropyl)silane was severely irritating to the eyes of rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the key skin irritation study, conducted according to OECD Test Guideline 404 and in compliance with GLP (Bushy Run Research Center, 1994), application of triethoxy(3-isocyanatopropyl)silane for 1-hour contact period to 2 rabbits resulted in severe erythema and edema, superficial or full thickness necrosis, ecchymoses, fissuring, desquamation, alopecia and scab formation. Irritiation was still present (severe in one animal) after 14 days. Following a 3-minute contact period to 6 rabbits similar effects were noted.

In the key eye irritation study, which pre-dated GLP but was conducted according to a guideline similar to OECD Test Guideline 405, (Chem Hygiene Fellowship, 1973) severe corneal damage and iritis was noted following application of 5, 15 or 100% triethoxy(3-isocyanatopropyl)silane.

Data for the hydrolysis product, 3-aminopropyl(triethoxy)silane (CAS 919-30-2), have been added to the dataset as supporting information for completeness, but are not required for the assessment of the skin and eye irritation potential of the parent as reliable data for it are available.

Justification for classification or non-classification

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