Reaction mass of 2-{[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and 2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-[2-(benzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-benzyl-2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-benzyl-N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride.

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

Study period:

1993-04-21 - 1993-04-28

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:

(1981)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

(1984)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approximately 12 weeks
- Weight at study initiation: 2198-2452 g
- Housing: The animals were housed under standard laboratory conditions. The animals were individually housed in labelled cages with perforated floors and equipped with an automatic drinking system (ITL, Bergen, The Netherlands). The animals were identified by ear tags.
- Diet: standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approximately 100 g/day. Certificates of analysis were examined and then retained in the RCC NOTOX archives.
- Water (ad libitum): tap-water diluted with decalcified water. Certificates of analysis were examined and then retained in the RCC NOTOX archives.
- Acclimation period: at least 5 days before start of treatment under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (fluctuations were observed, but were not considered to be relevant)
- Humidity (%): 55 (fluctuations were observed, but were not considered to be relevant)
- 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:

other: the other flank was treated the same way but without test item and served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 150 cm² (10 cm x 15 cm) of the dorsal area of the flank
- Type of wrap if used: surgical gauze patch (2 x 3 cm) mounted on microscope tape (3M, St. Paul, USA), wrapped with an elastic bandage (Coban, 3M, St. Paul, USA)

REMOVAL OF TEST SUBSTANCE
- Washing: by using a tissue moistened with tap-water and subsequently a dry tissue
- 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:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

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:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

There was no evidence of a corrosive effect on the skin.
One hour after exposure to the test item, very slight or well defined erythema and very slight or slight oedema were observed in the treated skin-areas of the animals. The erythema persisted for 48 h and had resolved in the animals within 7 days after exposure. The oedema had resolved within 48 h in two animals and within 72 hours after exposure in the third animal.

Other effects:

Remnants of the test substance were noted during the study, but had disappeared within 24 h after exposure in one animal and within 7 days in the other two animals.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured.

Interpretation of results:

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

Conclusions:

The test item was tested for primary skin irritation/corrosion according to the OECD TG 404 (1987) and in compliance with GLP. No mortality occured and and no signs of systemic toxicity were observed. The primary erythema score (mean out of all three animals over 24, 48, and 72 h) was determined to be 1.4, whereas effects were fully reversible within the 7 days of the post exposure period. The oedema score (mean out of all three animals over 24, 48, and 72 h) was determined to be 0.67, and the effects were fully reversible within 72 h. Hence, classification for skin irritation/corrosion according to 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

Study period:

1993-04-22 - 1993-05-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

(1984)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approximately 15 weeks
- Weight at study initiation: 2944 g
- Housing: The animal was housed under standard laboratory conditions. The animals was individually housed in a labelled cage with perforated floor and equipped with an automatic drinking system (ITL, Bergen, The Netherlands). The animal was identified by ear tag.
- Diet: standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approximately 100 g/day. Certificates of analysis were examined and then retained in the RCC NOTOX archives.
- Water (ad libitum): tap-water diluted with decalcified water. Certificates of analysis were examined and then retained in the RCC NOTOX archives.
- Acclimation period: at least 5 days before start of treatment under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (fluctuations were observed, but were not considered to be relevant)
- Humidity (%): 55 (fluctuations were observed, but were not considered to be relevant)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the other eye remained untreated and served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 ml

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

22 days

Number of animals or in vitro replicates:

1 male rabbit

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

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:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Instillation of the test item resulted in adverse effects on the cornea, iris, and the conjunctivae. One hour after instillation, severe redness and chemosis of conjunctivae (both maximal grade) corneal opacity grade 2 and iridic irritation grade 1 were observed. Similar reactions persisted after 24 h and grey/white discolouration of the eyelids and nictitating membrane, as a sign of necrosis, had become apparent. Treatment of the eyes with 2% fluorescein revealed a large area of the cornea showing epthelial damage (90%).
The corneal opacity (grade 2) and epithelial damage persisted until termination, although a slight recovery of the affected area was noted at the end of the observation period.
On days 3 and 4, redness was observed on the outside of the eyelids. Reduced elasticity of the eyelids was noted from day 8 onwards and was still present at termination. The signs of necrosis in the eyelids and/or nictitating membrane had disappeared within 14 days after instillation. The irritation of the conjunctivae had not completely resolved within the observation period. Redness (grade 2) and a small amount of discharge were observed at termination.
The iridic irritation had resolved within 14 days after instillation.
Discharge was observed (mean score 2.7 over 24, 48, and 72 h; max. 3), which was not fully reversible within 21 days.

Based on the results further testing in two subsequent animals was not carried out.

Other effects:

No staining of peri-ocular tissues by the test substance was observed.
No toxic symptoms were observed in the animal during the test period and no mortality occured.

Interpretation of results:

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

Conclusions:

The test item was tested in one rabbit for primary eye irritation/corrosion according to the OECD TG 405 (1987) and in compliance with GLP. The instillation of the test material resulted in adverse effects on the cornea, iris, and conjunctivae. Based on the results, further testing in two subsequent animals was not carried out. Hence, the test item has to be classified as irreversible effects on the eye (Cat 1) according to EC/1272/2008.

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 key study conducted according to the OECD TG 404 and in compliance with GLP, 3 male New Zealand White rabbits were exposed to 0.5 ml of the undiluted test substance for 4 h under semiocclusive conditions (NOTOX, 1993e). One hour after exposure to the test item, very slight or well defined erythema and very slight or slight oedema were observed in the treated skin-areas of the animals. The mean scores over 24, 48, and 72 h were 1.44 for erythema and 0.67 for oedema, with a maximum erythema and oedema score of 2. Remnants of the test substance were noted during the study, but had disappeared within 24 h after exposure in one animal and within 7 days in the other two animals. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Erythema and oedema were fully reversible within 7 days. In conclusion, the test substance is not considered to be a skin irritant.

Eye irritation:

In the key study conducted according to the OECD TG 405 and in compliance with GLP, 1 New Zealand White rabbit was instilled 0.1 ml of the undiluted test substance into the eye (NOTOX, 1993f). One hour after instillation, severe redness and chemosis of conjunctivae (both maximal grade), corneal opacity grade 2 and iridic irritation grade 1 were observed. Similar reactions persisted after 24 h and grey/white discolouration of the eyelids and nictitating membrane, as a sign of necrosis, had become apparent. Treatment of the eyes with 2% fluorescein revealed a large area of the cornea showing epithelial damage (90%). The mean scores over 24, 48, and 72 h were 2, 1, 3, and 3.3 for cornea, iris, redness, and chemosis, respectively. The corneal opacity (grade 2) and epithelial damage persisted until termination, although a slight recovery of the affected area was noted at the end of the observation period. On days 3 and 4, redness was observed on the outside of the eyelids. Reduced elasticity of the eyelids was noted from day 8 onwards and was still present at termination. The signs of necrosis in the eyelids and/or nictitating membrane had disappeared within 14 days after instillation. The irritation of the conjunctivae had not completely resolved within the observation period. Redness (grade 2) and a small amount of discharge were observed at termination. The iridic irritation had resolved within 14 days after instillation. Based on the results further testing in two subsequent animals was not carried out. In conclusion, the test substance is considered to cause irreversible effects on the eye.

Justification for classification or non-classification

The available data on skin irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

The test substance has to be classified as 'Eye irritant: Cat 1' (H318: Causes serious eye irritation) according to Regulation 1272/2008/EC, based on corneal opacity and conjunctivae redness, which were not reversible in the animal within the observation time.