Bis(trimethoxysilylpropyl)amine

Endpoint summary

Description of key information

Skin irritation (OCED TG 404): not irritating
Eye irritation (OECD TG 405): causes irreversible effects to the eye

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP. No information is given on the test material purity.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

use of 6 animals; observation period 7 d; rather occlusive conditions

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Fasting period before study: none
- Diet: appropriate commercial diet, ad libitum
- Water: municipal water, ad libitum

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

4 h

Observation period:

7 d

Number of animals:

3 male and 3 female rabbbits

Details on study design:

TEST SITE
- Type of wrap if used: gauze patch loosely covered with impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing: removal of test substance
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Reversibility:

not fully reversible within: 7d

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Irritant / corrosive response data:

In addition to the oedema and erythema scores (see table 1) desquamation and fissuring was observed. Desquamation was observed in all animals from day 1 to day 7. Fissuring was observed after 5 h in all animals and was only present in the females after 24 h. In 1 animal fissuring was still observed after 7 d. The chemical residue was apparent on the skin in all animals at all time points.

Table 1: Individual results of the skin irritation study.

Observation time	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
5 h	2	1	4	1	4	1	2	1	2	1	1	1
24 h	1	1	2	2	1	1	1	1	1	2	1	2
48 h	2	1	2	2	2	2	1	0	1	2	1	2
72 h	2	1	2	2	2	2	1	0	1	1	1	1
7 d	2	1	2	0	1	0	0	0	1	0	1	0
Mean value 24 + 48 + 72 h	1.66	1	2	2	1.66	1.66	1	0.33	1	1.66	1	1.66

Interpretation of results:

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

Conclusions:

The test item was investigated for skin irritation/corrosion broadly according to the OECD TG 404, but not in compliance with GLP. 0.5 ml of the undiluted test material was occlusively applied to the clipped skin of 3 male and 3 female New Zeeland White rabbits. After 4 h of exposure the test material was removed and the animals were maintained for a 7 day-observation period. The mean erythema and oedema scores were 1.4 each and were not fully reversible until study termination. In addition, desquamation and fissuring was observed. Desquamation was observed in all animals from day 1 to day 7, whereas fissuring was observed after 5 h in all animals and was only present in the females after 24 h. In one animal fissuring was still observed after 7 d. The chemical residue was apparent on the skin in all animals at all time points. The authors concluded the test item to be slightly irritating. Nevertheless, since mean animal scores do not exceed 1.4, the individual scores at 24, 48, and 72 h reading time points never exceeded a score of 2, and individual animal scores throughout the only 7 days lasting observation period give evidence that the effects are transient, classification for skin irritation according to 67/584/EEC and EC/1272/2008 is not warranted.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP. No information is given on the test material purity.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

use of 6 animals; dosage with 0.005 ml test substance

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Fasting period before study: none
- Diet: appropriate commercial diet, ad libitum
- Water: municipal water, ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.005 ml

Duration of treatment / exposure:

single treatment without washing

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein (2%)

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

1.22

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

2.61

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritant / corrosive response data:

At 24, 48, and 72 h several eyes were encrusted with dry pus. Some necrosis of the conjunctivae was observed at 1 (3/6 animals) and 4 h (5/6 animals).

Table 1: Results of the eye irritation study.

Rabbit #	Time	conjunctivae		iris	cornea
		redness	swelling
1	1 h	3	3	1	0
	24 h	3	4	1	1
	48 h	1	4	1	1
	72 h	2	2	1	1
	7 d	2	1	1	1
	14 d	0	0	0	0
	21 d	0	0	0	0
2	1 h	3	4	1	0
	24 h	2	4	1	1
	48 h	2	3	1	1
	72 h	3	3	1	1
	7 d	2	1	0	0
	14 d	0	0	0	0
	21 d	0	0	0	0
3	1 h	3	3	1	0
	24 h	3	4	1	1
	48 h	2	3	1	1
	72 h	3	4	1	2
	7 d	2	2	1	2
	14 d	0	0	0	0
	21 d	0	0	0	0
4	1 h	3	2	0	0
	24 h	3	4	1	1
	48 h	3	4	1	1
	72 h	3	4	1	2
	7 d	3	3	1	2
	14 d	0	0	0	0
	21 d	0	0	0	0
5	1 h	3	2	1	0
	24 h	3	4	1	1
	48 h	3	4	1	1
	72 h	2	4	1	1
	7 d	1	3	1	2
	14 d	3	2	1	1
	21 d	1	2	1	2
6	1 h	2	3	1	0
	24 h	3	4	1	1
	48 h	3	3	1	1
	72 h	3	4	- (opacity too great)	3
	7 d	3	4	- (opacity too great)	3
	14 d	3	3	2	3
	21 d	1	0	1	3
average score	1 h	2.83	2.83	0.83	0.0
	24 h	2.83	4.0	1.0	1.0
	48 h	2.33	3.5	1.0	1.0
	72 h	2.66	3.5	1.0 (out of 5 animals)	1.66
	24+48+72	2.61	3.67	1.0	1.22

Interpretation of results:

other: Category 1 (irreversible effects on the eye) based on CLP criteria (EU criteria according to Regulation (EC) No. 1272/2008)

Conclusions:

A generally reliable study, conducted similar to OECD 405 (not in compliance with GLP), reported that the neat test material caused significant irreversible effects and necrosis to the conjunctiva, iris and cornea of rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

In the available key study (Bushy Run Research Center, 1982a) the test item was investigated for skin irritation/corrosion according to a test protocol that is broadly in accordance with OECD TG 404, but not in compliance with GLP. 0.5 ml of the undiluted test material was occlusively applied to the clipped skin of 3 male and 3 female New Zealand White rabbits. After 4 h of exposure the test material was removed and the animals were maintained for a 7 day-observation period. The mean erythema and oedema scores were 1.4 each and the effects were not fully reversible until study termination. In addition, desquamation and fissuring was observed. Desquamation was observed in all animals from day 1 to day 7, whereas fissuring was observed after 5 h in all animals and was only present in the females after 24 h. In one animal fissuring was still observed after 7 days. The chemical residue was apparent on the skin in all animals at all time points. Nevertheless, since mean animal scores do not exceed 1.4, the individual scores at 24, 48, and 72 h reading time points never exceeded a score of 2, and individual animal scores throughout the only 7 days lasting observation period give evidence that the effects are transient, classification for skin irritation according to 67/584/EEC and EC/1272/2008 is not warranted.

 

Eye irritation/corrosion:

In the available key study (Bushy Run Research Center, 1982a) the test item was investigated for eye irritation related to corrosivity (see section 5.4.1) similar to the OECD TG 405, but not in compliance with GLP. 3 male and 3 female New Zealand White rabbits received 0.005 ml of the undiluted test material as a single treatment without consecutive washing. The neat test material caused significant irritation to the conjunctiva, iris and cornea of rabbits. Mean scores of all six animals over 24, 48, and 72 h were 1.22 for corneal damage, 1.0 for iritis, 2.61 for conjunctivae scores, and 3.67 for chemosis, respectively. The effects were not fully reversible until the end of the 21-day observation period. Moreover, at 24, 48, and 72 h several eyes were encrusted with dry pus. Some necrosis of the conjunctivae was observed at 1 h (3/6 animals) and 4 h (5/6 animals). Hence, the test item was concluded to cause severe damage to the eyes.

Justification for classification or non-classification

The available data are reliable and suitable for classification. Based on this data, the registered substance meets the criteria to be classified for irreversible effects on the eye (Cat 1, H318) according to EC/1272/2008. Classification for skin irritation according to 67/584/EEC and EC/1272/2008 is not warranted.