Bis(trimethoxysilylpropyl)amine

Endpoint summary

Description of key information

Oral (similar to OECD TG 401), rat: LD50 = 4200-8400 mg/kg bw (male) and 3780 mg/kg bw (female)
Dermal (similar to OECD TG 402), rabbit: LD50 = 16 800 mg/kg bw (male) and 11 865 mg/kg bw (female)
Inhalation: no reliable data available

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(no data on test material purity is given)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Hilltop-Wistar albino rats
- Weight at study initiation: 200-300 g
- Fasting period before study: yes (overnight)
- Diet: appropriate commercial diet, ad libitum
- Water: municipal water, ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: The test material was administered undiluted, since it reacted quickly with water under formation of a hard mass.

MAXIMUM DOSE VOLUME APPLIED: 16.0 ml/kg bw

Doses:

- 2.0, 4.0, 8.0, and 16.0 ml/kg bw as stated in the study report
- volumes applied correspond to doses of 2100, 4200, 8400, and 16800 mg/kg bw (converted from ml/kg bw based on a density of 1.05 g/ml, see IUCLID Section 4.4)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animal weights were recorded at day 0 (prior to dosing), and at days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

LD50 was calculated by the moving average method and is based on a 14 days observation period.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 4 - < 8 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Mortality: 2/5 (16 ml/kg bw); 0/5 (8 ml/kg bw); 2/5 (4 ml/kg bw)

Sex:

male

Dose descriptor:

LD50

Effect level:

> 4 200 - < 8 400 mg/kg bw

Based on:

test mat.

Remarks on result:

other: converted from ml/kg bw based on a density of 1.05 g/ml, see IUCLID Section 4.4

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 3.6 mL/kg bw

Based on:

test mat.

95% CL:

1.8 - 6.9

Remarks on result:

other: Mortaility: 4/5 (16 ml/kg bw); 0/5 (8 ml/kg bw); 3/5 (4 ml/kg bw)

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 3 780 mg/kg bw

Based on:

test mat.

95% CL:

1 890 - 7 245

Remarks on result:

other: converted from ml/kg bw based on a density of 1.05 g/ml, see IUCLID Section 4.4

Mortality:

Males:
- 16.0 ml/kg bw: 2/5 on days 2 and 5
- 8.0 ml/kg bw: 0/5
- 4.0 ml/kg bw: 2/5 on days 3 and 4
- 2.0 ml/kg bw: 0/5
Females:
- 16.0 ml/kg bw: 4/5 on days 1, 2, 2, and 6
- 8.0 ml/kg bw: 0/5
- 4.0 ml/kg bw: 3/5 on days 2, 3, and 8
- 2.0ml/kg bw: 0/5

Clinical signs:

other: Males: - 16.0 ml/kg bw: sluggishness at 5 min; unsteady gait at 2 h; prostration at 3 h; red, crusty discolouration on mouth and nose area at 1 day; survivors recovered at 2 days - 8.0 ml/kg bw: sluggishness at 5 min; recovery at 2 h - 4.0 ml/kg bw: gasp

Gross pathology:

Males:
- 16.0 ml/kg bw: in animals found dead: lungs dark red; stomachs filled with hard mass; in survivors: lungs dark red; lung of 1 male with white nodules
- 8.0 ml/kg bw: lungs with maroon patchy discolouration
- 4.0 ml/kg bw: in one animal found dead: dark red liver; in survivors: nothing remarkable
- 2.0 ml/kg bw: nothing remarkable was observed
Females:
- 16.0 ml/kg bw: in victims: lungs dark red; stomachs filled with hard mass; salivary glands with pus-filled nodule in one female; in survivors: lungs dark red; salivary glands enlarged
- 8.0 ml/kg bw: lungs mottled maroon and dark pink
- 4.0 ml/kg bw: in victims: lungs dark red; in survivors: lungs dark red; stomachs filled with hard mass
- 2.0ml/kg bw: nothing remarkable was observed

Other findings:

The authors report that the test item reacted very quickly with water to form a hard mass. Since a hard mass in stomachs was noted at necropsy, which was assumed to be reacted sample material, the deaths were concluded to be most likely due to obstruction of the stomach and intestine.

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 acute oral toxicity according to a protocol that is similar to the OECD TG 401, but without compliance with GLP. The test material was administered by stomach intubation to 5 Wistar rats each sex and dose group at doses of 2100, 4200, 8400, and 16 800 mg/kg bw. The LD50 was determined to be 4200-8400 mg/kg bw for males and 3780 mg/kg bw for females, respectively. The predominant clinical signs detected were sluggishness; unsteady gait; prostration; red, crusty discolouration on mouth and nose area; gaspping; salivation; and wheezing. Mean body weights were affected in high dose males and for females in all dose groups. Gross pathology revealed for animals found dead stomachs filled with hard mass; dark red lungs; or lungs with maroon pathy discolouration. One victim showed a dark red liver. Based on this data, classification for acute oral toxicity according to 67/584/EEC and EC/1272/2008 is not warranted.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 780 mg/kg bw

Quality of whole database:

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

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

There are no reliable data for the inhalation route. However, there is one study with a reliability score of 4.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

no data on test material purity is given; use of 4 animals per sex per dose level

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

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

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- Type of wrap if used: impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 h

TEST MATERIAL
- Constant volume used: no

Duration of exposure:

24 h

Doses:

Males:
- 8.0, 11.3, and 16.0 ml/kg bw as stated in the study report
- volumes applied correspond to doses of 8400, 11 865, and 16 640 mg/kg bw (converted from ml/kg bw based on a density of 1.05 g/ml, see IUCLID Section 4.4)
Females:
- 4.0, 8.0, and 16.0 ml/kg bw as stated in the study report
- volumes applied correspond to doses of 4200, 8400, and 16 800 mg/kg bw (converted from ml/kg bw based on a density of 1.05 g/ml, see IUCLID Section 4.4)

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animal weights were recorded at day 0 (prior to dosing), and on days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

LD50 was calculated by the moving average method and is based on a 14 days observation period.

Sex:

male

Dose descriptor:

LD50

Effect level:

16 mL/kg bw

Based on:

test mat.

95% CL:

8.43 - 30.6

Sex:

male

Dose descriptor:

LD50

Effect level:

16 800 mg/kg bw

95% CL:

8 851.5 - 32 130

Remarks on result:

other: converted from ml/kg bw based on a density of 1.04 g/ml, see IUCLID Section 4.4

Sex:

female

Dose descriptor:

LD50

Effect level:

11.3 mL/kg bw

Based on:

test mat.

95% CL:

5.09 - 25.2

Sex:

female

Dose descriptor:

LD50

Effect level:

11 865 mg/kg bw

Based on:

test mat.

95% CL:

5 344.5 - 26 460

Remarks on result:

other: converted from ml/kg bw based on a density of 1.04 g/ml, see IUCLID Section 4.4

Mortality:

Males:
8 ml/kg bw: 0/4
11.3 ml/kg bw: 0/4
16 ml/kg bw: 2/4
Females:
4 ml/kg bw: 0/4
8 ml/kg bw: 1/4
16 ml/kg bw: 3/4

Clinical signs:

other: Males: 8 ml/kg bw: none noted 11.3 ml/kg bw: unsteady gait at day 1 16 ml/kg bw: prostration of 2 animals at day 1 Females: 4 ml/kg bw: none noted 8 ml/kg bw: none noted 16 ml/kg bw: prostration at day 1 No further details are given in the study report

Gross pathology:

Males:
8 ml/kg bw: tracheae red; lungs of 1 was deep maroon
11.3 ml/kg bw: lungs of 2 were deep maroon
16 ml/kg bw: in animals found dead discoloured lungs (red or salmon) were observed; in survivors tracheae with red patches were observed; 1 bladder was filled with dark yellow fluid.
Females:
4 ml/kg bw: tracheae of 2 red, lungs of 2 with deep maroon patches
8 ml/kg bw: lungs of 1 mottled with with tan caseous nodules; lungs of 1 deep maroon; heart of 1 with white film like appearance on pericardial sac (histopathology revealed bronchopneumonia, pleuritis, pericarditis)
16 ml/kg bw: tracheae of 3 with dark red patches throughout; lungs of 1 mottled; liver of 1 mottled; bladder of 1 with dark fluid

Other findings:

- Local effects
Males:
8 ml/kg bw: edema, erythema, fissuring, desquamation
11.3 ml/kg bw: edema, erythema, fissuring, desquamation
16 ml/kg bw: edema, erythema, fissuring, desquamation
Females:
4 ml/kg bw: edema, erythema, fissuring, desquamation
8 ml/kg bw: edema, erythema, fissuring, desquamation, pus-filled nodules over dosed area
16 ml/kg bw: edema, erythema, fissuring, scabs

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 tested for acute dermal toxicity according to a test protocol that is comparable to the OECD TG 402, but without GLP compliance. The test material was occlusively administered to 4 New Zealand White rabbits each sex and dose group for 24 h. The doses applied were 8400, 11 865 and 16 800 mg/kg bw for males and 4200, 8400, and 16 800 mg/kg bw for females, respectively. The LD50 was determined to be 16 800 mg/kg bw (males) and 11 865 (females) mg/kg bw. The predominant clinical signs detected were unsteady gait and prostration, as well as local effects, such as oedema, erythema and desquamation. Gross pathology revealed red tracheae; lungs deep maroon, lungs mottled with with tan caseous nodules, and heart with white film like appearance on pericardial sac (histopathology revealed bronchopneumonia, pleuritis, pericarditis). Based on this data, classification for acute dermal toxicity according to 67/584/EEC and EC/1272/2008 is not warranted.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

11 865 mg/kg bw

Quality of whole database:

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

Additional information

Acute toxicity: oral

In the available key study (Bushy Run Research Center, 1982a) the test item was investigated for acute oral toxicity according to a protocol that is similar to the OECD TG 401, but without compliance with GLP. The test material was administered by stomach intubation to 5 Wistar rats each sex and dose group at doses of 2100, 4200, 8400, and 16 800 mg/kg bw. The LD50 was determined to be 4200-8400 mg/kg bw for males and 3780 for females, respectively. The predominant clinical signs detected were sluggishness; unsteady gait; prostration; red, crusty discolouration on mouth and nose area; gasping; salivation; and wheezing. Mean body weights were affected in high dose males and for females in all dose groups. Gross pathology revealed for animals found dead stomachs filled with hard mass; dark red lungs; or lungs with maroon patchy discolouration. One animal found dead showed a dark red liver.

Acute toxicity: dermal

In the available key study (Bushy Run Research Center, 1982a) the test item was tested for acute dermal toxicity according to a test protocol that is comparable to the OECD TG 402, but without GLP compliance. The test material was occlusively administered to 4 New Zealand White rabbits each sex and dose group for 24 h. The doses applied were 8400, 11 865 and 16 800 mg/kg bw for males and 4200, 8400, and 16 800 mg/kg bw for females, respectively. The LD50 was determined to be 16 640 (males) and 11 752 (females) mg/kg bw. The predominant clinical signs detected were unsteady gait and prostration, as well as local effects, such as oedema, erythema and desquamation. Gross pathology revealed red tracheae; lungs deep maroon, lungs mottled with tan caseous nodules, and heart with white film like appearance on pericardial sac (histopathology revealed bronchopneumonia, pleuritis, pericarditis).

Acute toxicity: inhalation

No reliable data is available for acute toxicity via inhalation. In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the inhalation route (required in Section 8.5.2 of REACH Annex VIII) does not need to be conducted as reliable data via the oral and dermal routes are available. Nevertheless, supporting data derived from a summary report is available (Bushy Run Research Center, 1982a). In this non-guideline study, which was not compliant to GLP, the test item was tested for acute inhalation toxicity. 5 Hilltop-Wistar albino rats each sex were exposed to substantially saturated vapour for 6 h. The vapour was produced by enclosing the test material in a sealed 120 l animal chamber for approximately 18 h (static concentration). Oxygen was added, as needed, to maintain a chamber oxygen content of approximately 20%. No deaths occurred throughout the study period. However, ataxia and slow righting reflex were observed after exposure. Gross pathology revealed no remarkable findings. The LC50 was found to be > vapour saturation at 23°C.

Justification for classification or non-classification

The available data are reliable and suitable for classification. Based on this data, classification for acute toxicity according to 67/584/EEC and EC/1272/2008 is not warranted.