Bis(triethoxysilylpropyl)amine

Endpoint summary

Description of key information

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

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:

01 – 30 Sep 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit

Species:

rabbit

Strain:

other: New Zealand White Rabbits Crl:KBL (NZW)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 22 - 30 weeks old
- Weight at study initiation: > 2 kg
- Housing: ABS-plastic rabbit cages, floor 4200 cm²
- Diet: autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 0724) ad libitum rich in crude fibre
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: An untreated patch at the right side of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) 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 and continued for day 4 to day 14

Number of animals:

2 males

Details on study design:

TEST SITE
- Area of exposure: 6 cm² on the left side of the dorsal area
- Type of wrap if used: gauze was held in place with a non-irritating tape, patch was fixed with semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, at the end of the exposure period (4 h) the residual test item was removed with tap water
- Time after start of exposure: 4 h

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 fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritant / corrosive response data:

After 1 h both animals showed erythema and oedema reactions (grade 1). The erythema scores were increasing up to 72 h (grade 2), and were not fully reversible within 14 days. Edema scores increased after 24 h (grade 2) only in animal 1, but were fully reversible within 72 h (animal 1) to 5 days (animal 2). Desquamation was observed at the treated site in animal 1 from day 4 to 7 and in animal 2 from day 6 to 8.

Other effects:

Neither mortalities nor significant clinical signs of toxicity were observed. There were no significant body weight changes during the contact and observation period.

Interpretation of results:

other: CLP/EU GHS criteria are met, Category 2 (irritant) classification required according to Regulations (EC) No 1272/2008

Conclusions:

CLP: Skin irrit 2, H315

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:

06 Oct - 03 Nov 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit

Species:

rabbit

Strain:

other: New Zealand White Rabbits Crl:KBL (NZW)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 26 - 28 weeks old
- Weight at study initiation: > 2 kg
- Housing: ABS-plastic rabbit cages, floor 4200 cm²
- Diet: autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 0724) ad libitum rich in crude fibre
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated contralateral 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):

13 days
Reading time points: 1, 24, 48, and 72 h and daily up to 13 days post-application

Number of animals or in vitro replicates:

2 females

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 11 d

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 d

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 6 d

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 9 d

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 13 d

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 13 d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 13 d

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 10 d

Irritant / corrosive response data:

One hour post exposure, effects on iris (grade 1, 2/2 animals), conjunctivae redness (grade 1 and 2, 2/2 animals) and chemosis (grade 3, 2/2 animals), were observed. In addition, discharge (grade 2) was observed in both animals at 1 h and was fully reversible within 13 days. Mean values over 24, 48, and 72 h for cornea were 0.67 and 1, respectively. After 48 h in both animals corneal opacity was 100% and the irises were red and discoloured. After 72 h cornea opacity was 50% in animal 1 and 2. Mean scores over 24, 48, and 72 h for iris were 0.67 and 1 respectively. Conjuntivae redness mean scores were 2 and 3, respectively. Chemosis mean score was 2.33 in both animals. Any effect observed was fully reversed at the end of the observation period.

Other effects:

The body weight development of both animals during the observation period was within the expected range.

Interpretation of results:

other: CLP/EU GHS criteria are met, Category 2 (irritating to eyes) classification required according to Regulations (EC) No 1272/2008

Conclusions:

CLP: eye irrit. Cat. 2 (H319)

Under the conditions of the present study, a single ocular application of the test item Bis(triethoxysilylpropyl)amine to rabbits at a dose of 0.1 mL produced irritant effects, which were fully reversible within 13 days. Neither mortalities nor significant clinical signs of toxicity were observed.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Two studies for the assessment of the skin irritating properties of 3-(triethoxysilyl)-N-[3-(triethoxysilyl)propyl]-1-propanamine (CAS 13497-18-2) are available. Both were conducted according to OECD TG 404, the more recent one also in compliance with GLP (BSL, 2014 and ASTA Pharma AG, 1988).

 

The skin irritation properties of 3-(triethoxysilyl)-N-[3-(triethoxysilyl)propyl]-1-propanamine (CAS 13497-18-2) were tested in an in vivo study according to OECD TG 404 under GLP conditions (BSL, 2014). In the study, 0.5 mL of undiluted test substance was applied to the clipped skin of two male New Zealand White rabbits (Crl:KBL) for 4 hours using a semi-occlusive dressing. The treated skin was observed and evaluated at 1, 24, 48 and 72 h post-application and continued for day 4 to day 14. One hour post application both animals showed erythema and edema reactions (grade 1). The erythema scores were increasing up to 72 h (grade 2), and were not fully reversible within 14 days. Edema scores increased after 24 h (grade 2) only in animal 1, but were fully reversible within 72 h (animal 1) to 5 days (animal 2). Desquamation was observed at the treated site in animal 1 from day 4 to 7 and in animal 2 from day 6 to 8. Neither mortalities nor significant clinical signs of toxicity were observed. There were no significant body weight changes during the contact and observation period. In conclusion the test substance was irritating to the skin under the conditions of the test.

 

In the second skin irritation study according to OECD TG 404, 3 Russian White rabbits were treated with 0.5 ml of the undiluted test substance for 4 h under occlusive conditions. Erythema and edema reactions were scored according to the Draize scoring system. No mortality and no clinical signs of toxicity were observed throughout the study. After 1 h all animals showed erythema and edema reactions (grade 1). The scores were increasing up to 72 h (grade 2-3), but were fully reversible within 14 d. The mean scores over 24, 48, and 72 h were 1.7, 2.7, 2 for erythema and 2.3, 3, 3 for edema, respectively in the individual animals. After the first week desquamation was observed. In conclusion the test substance was irritating to the skin under the conditions of the test.

 

Eye irritation

Two studies for the assessment of the eye irritating properties of 3-(triethoxysilyl)-N-[3-(triethoxysilyl)propyl]-1-propanamine (CAS 13497-18-2) are available. Both were conducted according to OECD TG 405, the more recent one also in compliance with GLP (BSL, 2015 and ASTA Pharma AG, 1988).

 

An eye irritation test is available with 3-(triethoxysilyl)-N-[3-(triethoxysilyl)propyl]-1-propanamine (CAS 13497-18-2), which was performed in New Zealand White rabbits according to OECD TG 405 and in compliance with GLP (BSL, 2015). Pure test substance (0.1 ml) was instilled into the eye of 2 female animals as a single treatment without rinsing of the eye. Both eyes of each rabbit were examined macroscopically for ocular irritation using a handheld penlight in accordance with the method of Draize at 1, 24, 48 and 72 hours and daily up to 13 days post-application. After 1 h post exposure, effects on iris (grade 1 in 2/2 animals), conjunctivae redness (grade 1+2) and chemosis (grade 3, in 2/2 animals) were observed. In addition, discharge (grade 2) was observed in both animals at 1 h and was fully reversible within 13 days. Mean values over 24, 48, and 72 h for cornea as well as for iris were 0.67 and 1, respectively. Conjunctivae redness, mean scores were 2 and 3, respectively. Chemosis, mean score was 2.3 in both animals. Any effect observed was fully reversed at the end of the observation period. In conclusion, based on the effects observed (mean scores and reversibility of effects) 3-(triethoxysilyl)-N-[3-(triethoxysilyl)propyl]-1-propanamine was irritating to eyes.

 

Another eye irritation test is available with 3-(triethoxysilyl)-N-[3-(triethoxysilyl)propyl]-1-propanamine (CAS 13497-18-2), which was performed in Russian White rabbits according to OECD TG 405 (ASTA Pharma AG, 1988). Pure test substance (0.1 ml) was instilled into the eye of 3 male animals as a single treatment without rinsing of the eye. Both eyes of each rabbit were examined macroscopically for ocular irritation using a handheld penlight in accordance with the method of Draize at 1, 24, 48 and 72 hours and 4, 7, 14, and 21 days after dosing. After 1 h post exposure, effects on cornea (grade 1, area 4, in 3/3 animals), iris (grade 1, in 1/3 animals), conjunctivae redness (grade 1, in 2/3 animals) and chemosis (grade 2, in 3/3 animals) were observed. In addition, discharge (grade 3) was observed in all animals at 1 h and was fully reversible within 14 days. Discharge was white/yellow and accompanied by alopecia around the eye (2 cm radius) during week 2 and 3 for each animals. Mean values over 24, 48, and 72 h for cornea were 1, 1.7, and 1.7 respectively. The area affected was given as grade 4 in all animals until day 4. At day 7 only one animal showed an effect on the cornea (area grade 2). Iris mean scores were 1, 0.2, and 1, respectively. Conjunctivae redness, mean scores were 2, 2.3, and 2.7, respectively. Chemosis, mean scores were 2.3, 2.7, and 2.7, respectively. Any effect observed was fully reversed at the end of the observation period. In conclusion, based on the effects observed (mean scores and reversibility of effects) 3-(triethoxysilyl)-N-[3-(triethoxysilyl)propyl]-1-propanamine was irritating to eyes.  

Justification for classification or non-classification

The available data on skin irritation of the test substance meet the criteria for classification as “Skin irritant, category 2” with the hazard statement “Causes skin irritation (H315)” according to Regulation (EC) No. 1272/2008.

The available data on eye irritation of the test substance meet the criteria for classification as “Eye irritant, category 2” with the hazard statement “Causes serious eye irritation (H319)” according to Regulation (EC) No. 1272/2008.