N-[3-(trimethoxysilyl)propyl]butylamine

Endpoint summary

Description of key information

Skin irritation (OECD TG 404): irritating (RA CAS 3069-25-8)
Eye irritation (OECD TG 405): causes irreversible effects to the eye (RA CAS 3069-25-8)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 17 days

Remarks on result:

other: no eschar formation observed

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: eschar formation after 72 h, fully reversible within 6 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: eschar formation after 72 h with detachment within 10 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

In this study with the structural analogue N-methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) it was observed that the source substance is not irritating to skin according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The chemical was applied in 0.01 mL amounts to clipped, uncovered intact skin of 5 rabbit bellies either undiluted or in progressive dilutions of 10, 1, 0.1, 0.01% in solvent. Additionally, a 4 h contact test (occlusive application) for the testing of corrosivity was performed. One of 10 grades is assigned based on appearence of moderate or marked capillary injection, erythema, oedema, or necrosis within 24 h. No injury from undiluted test material = Grade 1.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: none
- Diet: appropriate diet ad libitum (not further specified)
- Water: ad libitum (not further specified)

Type of coverage:

other: Both open and occlusive was tested.

Preparation of test site:

shaved

Vehicle:

other: Both undiluted and diluted in solvent (not further specified) was tested.

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.01 mL
- Concentration (if solution): 10, 1, 0.1, 0.01% in solvent

Duration of treatment / exposure:

4 h

Observation period:

24 h

Number of animals:

5 animals (not further specified) for open administration, 6 animals (not further specified) for occlusive administration.

Details on study design:

TEST SITE
- Area of exposure: abdomen

SCORING SYSTEM: One of 10 grades is assigned based on appearence of moderate or marked capillary injection, erythema, oedema, or necrosis within 24 h. No injury from undiluted test material = Grade 1.

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

out of all animals tested

Time point:

24 h

Score:

4

Max. score:

10

Reversibility:

no data

Remarks on result:

other: The undiluted test material was openly applied and caused marked capillary injection on 4 rabbits and moderate erythema in one animal.

Irritation parameter:

other: necrosis

Basis:

mean

Remarks:

out of all 6 animals tested

Time point:

24 h

Score:

0

Max. score:

10

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: The test material was occlusively applied to the rabbits for 4 h and did not cause necrosis. Hence, the test material was found to be "not corrosive".

Other effects:

No further effects were reported.

Interpretation of results:

study cannot be used for classification

Conclusions:

The test item was tested for its skin irritating properties in a non-guideline study and without GLP compliance. The chemical was applied in 0.01 mL amounts to clipped, uncovered intact skin of 5 rabbit abdomen either undiluted or in progressive dilutions of 10, 1, 0.1, 0.01% in solvent. Additionally, a 4 h contact test (occlusive application) for the testing of corrosivity was performed. The undiluted test material was opnely applied and caused marked capillary injection on 4 rabbits and moderate erythema in one animal. Furthermore, the test material was occlusively applied to the rabbits for 4 h and did not cause necrosis. Hence, the test material was found to be "not corrosive". In conclusion, the test material was found to be irritating under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Only the eyes of rabbits not staining with 5% fluorescein in 20 s contact were accepted for the study. Single instillation of 0.005, 0.02, 0.1, or 0.5 ml undiluted or 0.5 ml of 40, 15, 5, or 1% test material dilutions were made into the conjunctival sac of 5 rabbits. The eyes were read immidiately unstained and after fluorescein at 24 h, with 1 of 10 grades assigned. Trace or no injury from undiluted test material = Grade 1.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Fasting period before study: none
- Diet: appropriate diet ad libitum (not further specified)
- Water: ad libitum (not further specified)

Vehicle:

other: Both undiluted and diluted in propylene glycol (PG) was tested.

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.005, 0.02, 0.1, or 0.5 ml undiluted or 0.5 ml of dilutions
- Concentration (if solution): 40, 15, 5, or 1%

Duration of treatment / exposure:

24 h

Observation period (in vivo):

24 h

Number of animals or in vitro replicates:

5 (not further specified)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: 1 of 10 grades assigned. Trace or no injury from undiluted test material = Grade 1.

TOOL USED TO ASSESS SCORE: with and without fluorescein

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

over all animals tested

Time point:

other: 24 h

Score:

9

Max. score:

10

Reversibility:

not specified

Remarks on result:

other: Severe corneal injury with irritis from 0.005 ml undiluted test material per eye; moderate to severe corneal injury with irritis one animal treated with 0.5 ml of 5% test material diluted in PG; no injury on 5 eyes from 1% test material in PG

Other effects:

No further effects were reported.

Interpretation of results:

study cannot be used for classification

Conclusions:

The test item was tested for its eye irritating properties in a non-guideline study and without GLP compliance. Single instillation of 0.005, 0.02, 0.1, or 0.5 ml undiluted or 0.5 ml of 40, 15, 5, or 1% test material dilutions in propylene glycol were made into the conjunctival sac of 5 rabbits. Severe corneal injury with irritis from 0.005 ml undiluted test material per eye and moderate to severe corneal injury with iritis on one animal treated with 0.5 ml of 5% test material diluted in propylene glycol were oserved. No injury was observed in 5 eyes treated with 1% test material in propylene glycol. Hence, the test item was concluded to cause severe damage to the eyes.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

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

Remarks on result:

other: cornea opacity (grade 2) persisted after 21 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 21 days

Remarks on result:

other: iridial effects (grade 1) persisted after 21 days (circumcorneal injection from day 6 until study termination)

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 21 days

Remarks on result:

other: redness (grade 2) persisted after 21 days, necrotic conjunctival sac and haw observed after 24 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: chemosis (grade 1) persisted after 21 day

Interpretation of results:

other: CLP/EU GHS criteria are met, Category 1 (irreversible effects on the eye) classification required according to Regulations (EC) No 1272/2008

Conclusions:

In the available OECD TG 405 study from the structural analogue N-methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) serious eye damage (Eye Dam. 1) according to Regulation (EC) No 1272/2008 was noted.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No reliable information on skin irritation/corrosion and eye irritation are available for the registered substance, N-[3-(trimethoxysilyl)propyl]-1-butanamine (CAS 31024-56-3).

Therefore, read across from the structurally similar source substance N-methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) was applied. In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and in accordance with the Read across assessment framework (RAAF, ECHA 2017) read across from analogue substances has been applied to support the human health hazard assessment of N-[3-(trimethoxysilyl)propyl]-1-butanamine (CAS 31024-56-3). Details on read across justification can be found in the justification for grouping of substances attached in IUCLID Section 13.

 

Skin irritation/corrosion:

N-[3-(Trimethoxysilyl)propyl]-1-butanamine (CAS 31024-56-3) was tested for its skin irritating properties in a non-guideline study and without GLP compliance (Bushy Run Research Center, 1981). The study was determined to be reliability 4 (documentation insufficient for assessment). 0.01 mL of the registered substance was applied to clipped, uncovered, intact skin of 5 rabbits abdomens either undiluted or in progressive dilutions of 10, 1, 0.1, and 0.01% in the solvent. Additionally, a 4 h contact test (occlusive application) for the testing of corrosivity was performed. The undiluted test material was openly applied and caused marked capillary injection on 4 rabbits and moderate erythema in one animal. No individual scores were given in the study report.

Furthermore, the test material was occlusively applied to the rabbits for 4 h and did not cause necrosis. Hence, N-[3-(trimethoxysilyl)propyl]-1-butanamine was found to be "not corrosive".

N-Methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) was investigated for skin irritation/corrosion according to the OECD TG 404, but not in compliance with GLP (Hüls AG, 1989). 3 male Small White Russian rabbits were administered 0.5 mL of the undiluted test substance for 4 h under semiocclusive conditions. 1, 24, 48, and 72 h, as well as 6, 8, 10, 13, 17, and 21 days after removal of the test item the skin reactions were recorded. The mean erythema scores over 24, 48, and 72 h noted were 2.67, 1, and 2, respectively, and the mean oedema scores were 2, 0.3, and 2, respectively. In one animal showing the strongest erythema reaction, the effect was reversible within 17 days.

Classification for skin irritation Cat. 2, according to Regulation (EC) No. 1272/2008, is warranted, if two or more animals show mean erythema or oedema scores of 2.3 or more. According to these criteria N-methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) does not need to be classified since only one animal showed erythema scores above the score of 2.3 and reversibility within the observation period of 21 days (Hüls AG, 1989). Nevertheless, mild irritation potential can be concluded for CAS 3069-25-8 since mean values between 1.5 and 2.3 for erythema and/or oedema from gradings in 2 of 3 tested animals from readings at 24, 48, and 72 hours are observed. The acute dermal toxicity study (Bushy Run Research Center, 1981) further supports the irritation potential of the registered substance, as erythema, oedema and necrosis were the predominant clinical signs seen in the animals treated with N-[3-(trimethoxysilyl)propyl]-1-butanamine (CAS 31024-56-3).

In conclusion, as a worst case N-[3-(trimethoxysilyl)propyl]-1-butanamine (CAS 31024-56-3) was considered to be irritating to the skin.

 

Eye irritation:

N-[3-(trimethoxysilyl)propyl]-1-butanamine (CAS 31024-56-3) was tested for its eye irritating properties in a non-guideline study and without GLP compliance (Bushy Run Research Center, 1981). The study was determined to be reliability 4 (documentation insufficient for assessment). Single instillation of 0.005, 0.02, 0.1, or 0.5 ml undiluted or 0.5 ml of 40, 15, 5, or 1% test material dilutions in propylene glycol were made into the conjunctival sac of 5 rabbits. Severe corneal injury with iritis was noted from 0.005 ml of undiluted test material per eye. In another dose group, moderate to severe corneal injury with iritis was observed in one animal treated with 0.5 ml of 5% test material diluted in propylene glycol. No injury was observed in 5 eyes treated with 1% test material in propylene glycol. No individual scores were given in the study report. Hence, N-[3-(trimethoxysilyl)propyl]-1-butanamine (CAS 31024-56-3) was concluded to cause serious damage to the eyes.

In the available study (Hüls AG, 1989) with the source substance N-methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) conducted according to the OECD TG 405, but not in compliance with GLP, 1 Small White Russian rabbit was instilled with 0.1 ml of the undiluted N-methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) into the eye. It is not stated in the study report whether the test item was administered into both eyes or one eye remained untreated and served as a control. After 1 h, severe redness and chemosis of the conjunctiva, corneal opacity grade 3 and iridic irritation grade 1 were observed. Moreover, iris reaction was delayed. Similar reactions persisted after 24 h and necrosis of the nictitating membrane and the conjunctiva was observed, in addition to strongly reddened iris in combination with haemorrhage. Treatment of the eyes with fluorescein revealed opacity of an area greater than three quarters up to the whole area. The mean scores over 24, 48, and 72 h were 2, 1, 3, and 1 for cornea, iris, redness, and chemosis, respectively. Only the noted chemosis was reversible within 21 days; all other damages were still persistent at study termination. Since the measured pH value of the test item was 12.3, only one animal was tested for acute eye irritation in this study. It can be concluded that the severe eye effects could be due to the strong alkalinity of the test substance. Based on this result, N-methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) is considered to cause irreversible effects on the eye.

Justification for classification or non-classification

The available data on irritation/corrosion meets the criteria for classification as Skin Irrit. 2 (H315) and as Eye Damage 1 (H318) according to Regulation (EC) No. 272/2008.