N-methyl-3-(trimethoxysilyl)propylamine

Endpoint summary

Description of key information

Skin irritation (OECD 404), rabbit: not irritating
Eye irritation (OECD 405), rabbit: irritating (Eye Dam 1)

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:

21 Nov - 12 Dec 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study conducted according to the appropriate OECD test guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: White Russian (Chbb)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Carl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2100 - 2300 g
- Housing: Animals were housed individually in stainless steel cages
- Diet: K4 diet for rabbits (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 ml

Duration of treatment / exposure:

4 h

Observation period:

21 days
Reading time points: 1, 24, 48 and 72 h and 6, 8, 10, 14, 17 and 21 days

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: dorsal/lateral trunk
- Type of wrap if used: The exposure area (6 cm²) was covered with elastic gauze.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed using warm water after the exposure period.
- 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:

2.67

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:

0.33

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

Irritant / corrosive response data:

Well-defined erythema (grade 2 in 3/3 animals) and edema (grade 1 in 2/3 animals, grade 2 in 1/3 animals) formation was observed in 3/3 animals 1 h after removal of the test material. Moderate to severe erythema (grade 3) formation was observed in the first animal 24 h after removal of the test material but was fully reversible within 17 days. Slight edema (grade 2) formation was observed 24 h after removal of the test material in the same animal, being fully reversible within 6 days. Very slight erythema (grade 1) formation was still recorded in the second animal within 24 h, but was fully reversible within 6 days (including slight eschar formation after 72 h). Very slight edema (grade 1) formation persisted 24 h after removal of the test material and was fully reversible within 48 h. The third animal showed well--defined erythema (grade 2) formation until 72 h after removal of the test material including slight eschar formation after 72 h. Erythema and eschar formation were fully reversible within 8 and 10 days, respectively. Moderate to severe edema (grade 3) formation was observed at the 24 h reading time point but was fully reversible within 6 days.

Other effects:

No symptoms of systemic toxicity were observed in any animal during the test period and no mortality occurred during the course of the study.

Table 1: Summary of individual skin reaction

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
24 h	3	2	1	1	2	3
48 h	3	2	1	0	2	2
72 h	2	2	1	0	2	1
Mean value 24 + 48 + 72 h	2.67	2	1	0.33	2	2

Interpretation of results:

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

Conclusions:

In an in vivo skin irritation study in the rabbits and according to OECD guideline 404 no signs of systemic toxicity were observed in the animals during the test period and no mortality occurred. Therefore, the test material is considered to be classified as a non-irritant to the skin.

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:

29 Nov - 20 Dec 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study conducted according to the appropriate OECD test guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: White Russian (Chbb)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Carl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2200 g
- Housing: Animal was housed individually in a stainless steel cage
- Diet: K4 diet for rabbits (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 ml

Duration of treatment / exposure:

24 h

Observation period (in vivo):

21 days
Reading time points: 1, 24, 48 and 72 h and 6, 8, 10, 13, 17 and 21 days

Number of animals or in vitro replicates:

1 male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The treated eye was washed with warm physiological NaCl solution after the exposure period with the test material.
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: eye lamp / fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

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 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 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:

not reversible

Remarks on result:

other: chemosis (grade 1) persisted after 21 days

Irritant / corrosive response data:

Cornea opacity (grade 3) was observed immediately (1 h) after exposure with the test material and was slightly reverted within 24 h (grade 2). Nevertheless, corneal opacity persisted until study termination after 21 days (grade 2). Iridial effects (grade 1) were also noted 1 h after exposure with the test material and persisted until study termination (grade 1). Additionally, the iris appeared flushed and bloody (Days 1 - 13) and circumcorneal injection was observed from Days 6 to 21 (study termination) demonstrating irreversible iridial effects. Conjunctival effects (redness, grade 3)) were observed 1 h after exposure with the test material until Day 13 of the study. From Days 13 - 21 conjunctival effects were still observed to a lesser extend (grade 2) but indicating irreversible effects. Chemosis (grade 2) was also recorded 1 h after exposure with the test material but was slightly reverted (grade 1) within 24 h and persisted until study termination. The results of this test indicate the substance to be a severe irritant to the eye using the procedure described. Thus, according to OECD TG further testing for ocular irritancy should not be performed with additional animals.

Other effects:

No symptoms of systemic toxicity were observed in any animal during the test period and no mortality occurred during the course of the study.

Table 1: Summary of individual eye effects

Observation time	Cornea	Iris	Conjunctivae (rednee)	Chemosis
1 h	3	1	3	2
24 h	2	1	3	1
48 h	2	1	3	1
72 h	2	1	3	1
6 d	2	circumcorneal injection	3	1
8 d	2	circumcorneal injection	3	1
10 d	2	circumcorneal injection	3	1
13 d	2	circumcorneal injection	3	1
17 d	2	circumcorneal injection	2	1
21 d	2	circumcorneal injection	2	1
Mean value of 24 + 48 + 72 h	2	1	3	1

Interpretation of results:

other: CLP/EU GHS Category 1 (H318) according to Regulation (EC) No 1272/2008

Conclusions:

In an in vivo acute eye irritation/corrosion study in the rabbit according to OECD guideline 405 no signs of systemic toxicity were observed in the animals during the test period and no mortality occurred. However, the results of this test indicate the substance to be a severe irritant to the eye using the procedure described. Thus, according to OECD guideline 405 further testing for ocular irritancy should not be performed with additional animals and thus, the test material is considered to be classified as severe eye irritant (Eye Dam. Cat 1, H318) according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In the reliable skin irritation study performed with the registered substance N-methyl-3-(trimethoxysilyl)propylamine (CAS 3069-25-8) according to OECD TG 404 three male White Russian (Chbb) rabbits were exposed to 0.5 mL of the neat test material for 4 hours applied onto the shaved skin via semi-occlusive dressing (Hüls AG, 1989b). Skin reactions were evaluated according to the Draize scoring system 1, 24, 48 and 72 hours and 6, 8, 10, 14, 17 and 21 days post-application. No symptoms of systemic toxicity were observed in any animal during the test period and no mortality occurred during the course of the study. Well-defined erythema (grade 2 in 3/3 animals) and edema (grade 1 in 2/3 animals, grade 2 in 1/3 animals) formation was observed in 3/3 animals 1 h after removal of the test material. Moderate to severe erythema (grade 3) formation was observed in the first animal 24 h after removal of the test material but was fully reversible within 17 days. Slight edema (grade 2) formation was observed 24 h after removal of the test material in the same animal, being fully reversible within 6 days. Very slight erythema (grade 1) formation was still recorded in the second animal within 24 h, but was fully reversible within 6 days (including slight eschar formation after 72 h). Very slight edema (grade 1) formation persisted 24 h after removal of the test material and was fully reversible within 48 h. The third animal showed well--defined erythema (grade 2) formation until 72 h after removal of the test material including slight eschar formation after 72 h. Erythema and eschar formation were fully reversible within 8 and 10 days, respectively. Moderate to severe edema (grade 3) formation was observed at the 24 h reading time point but was fully reversible within 6 days. In summary, the mean values for erythema and edema after 24/48/72 h were calculated to be 2.67, 1, 2 and 2, 0.33, 2, respectively. Thus, the substance is not considered to be a skin irritant.

 

Eye irritation

In the reliable eye irritation study performed with N-methyl-3-(trimethoxysilyl)propylamine (CAS 3069-25-8) according to OECD TG 405 (Hüls AG, 1989c) 0.1 mL of the neat test material was instilled in the eye of one male White Russian (Chbb) rabbit. The eye was examined and the changes were graded according to the Draize scoring system 1, 24, 48 and 72 hours and 6, 8, 10, 13, 17 and 21 days post-application. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred during the course of the study. Cornea opacity (grade 3) was observed immediately (1 h) after exposure with the test material and was slightly reverted within 24 h (grade 2). Nevertheless, corneal opacity persisted until study termination after 21 days (grade 2). Iridial effects (grade 1) were also noted 1 h after exposure with the test material and persisted until study termination (grade 1). Additionally, the iris appeared flushed and bloody (Days 1 - 13) and circumcorneal injection was observed from Days 6 to 21 (study termination) demonstrating irreversible iridial effects. Conjunctival effects (redness, grade 3)) were observed 1 h after exposure with the test material until Day 13 of the study. From Days 13 - 21 conjunctival effects were still observed to a lesser extent (grade 2) but indicating irreversible effects. Chemosis (grade 2) was also recorded 1 h after exposure with the test material but was slightly reverted (grade 1) within 24 h and persisted until study termination. The results of this test indicate the substance to be a severe irritant to the eye using the procedure described. Thus, according to OECD TG further testing for ocular irritancy should not be performed with additional animals. In conclusion, the registered substances N-methyl-3-(trimethoxysilyl)propylamine (CAS 3069-25-8) has to be classified as Eye Dam. 1, H318 according to Regulation (EC) No 1272/2008.

Justification for classification or non-classification

The available data on skin irritation/corrosion of N-methyl-3-(trimethoxysilyl)propylamine do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.

Based on the available data on serious eye damage/eye irritation of N-methyl-3-(trimethoxysilyl)propylamine the registered substance has to be classified as Eye Dam. 1, H318 according to Regulation (EC) No 1272/2008.