N-[3-(trimethoxysilyl)propyl]butylamine

Endpoint summary

Description of key information

Oral (similar to OECD TG 401), rat: LD50 = 12 825 mg/kg bw (male)
Dermal (similar to OECD TG 402), rabbit: LD50 = 15 200 mg/kg bw (male)
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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3-4 weeks
- Weight at study initiation: 90-120 g
- Fasting period before study: none
- Diet: appropriate diet ad libitum (not further specified)
- Water: ad libitum (not further specified)

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 16 mL/kg

Doses:

0.5, 1, 2, 4, 8, and 16 mL/kg bw, equivalent to 475, 950, 1900, 3800, 7600, and 15200 mg/kg bw (calculated based on a density of 0.95 g/cm³)

No. of animals per sex per dose:

5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The LD50 along with the 95% confidence limits was calculated by the moving average method based on a 14 day observation period.

Sex:

male

Dose descriptor:

LD50

Effect level:

12 825 mg/kg bw

Based on:

test mat.

95% CL:

>= 551 - <= 3 192

Remarks on result:

other: (equivalent to 13.5 mL/kg bw (95% CL 5.38 - 33.6 mL/kg bw); calculated based on a density of 0.95 g/cm³)

Sex:

male

Dose descriptor:

LD0

Effect level:

475 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (equivalent to 0.5 mL/kg bw; calculated based on a density of 0.95 g/cm³)

Mortality:

- 16 mL/kg bw: 3/5 (all animals died 30-35 min after dosing)
- 8 mLl/kg bw: 1/5 (animal died on day 7 post-dosing)
- 4 mL/kg bw: 2/5 (animals died 20 min after dosing and on day 1); repeated for confirmatory purpose: deaths 2/5 on days 0 and 1
- 2 mL/kg bw: 2/5 (deaths occured 15 and 20 min after dosing)
- 1 ml/kg bw: 1/5 (animal died 30 min after dosing)
- 0.5 mL/kg bw: 0/5

Clinical signs:

other: - 16 mL/kg bw: Sluggish (survivers) at 35 min; salivation - 8 mL/kg bw: Diarrhoea at day 1 - 4 mL/kg bw: Salivation; repeated for confirmatory purpose: Unsteady gait; salivation 5 min after dosing; survivors recovered after 1 day. - 2 mL/kg bw: Unsteady g

Gross pathology:

In victims, the stomach was gas-filled, the glandular portions were injected, and the intestines were injected or contained blood.
In survivors, nothing remarkable was observed.

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 oral toxicity according to a test protocol that is comparable to the appropriate OECD 401 test guideline, but without GLP compliance. The test material was administered by stomach intubation to 5 male rats each dose group. The LD50 was determined to be 12825 mg/kg bw. The predominant clinical signs detected were salivation, unsteady gait, sluggishness, and diarrhoea. No deaths and no clinical signs throughout the study period were observed at 425 mg/kg bw. Based on this data, classification for acute oral toxicity according to Regulation (EC) No. 1272/2008 is not warranted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

12 825 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

(only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3-5 months
- Fasting period before study: none
- Diet: appropriate diet ad libitum (not further specified)
- Water: ad libitum (not further specified)

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Type of wrap if used: impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess fluid was removed to prevent ingestion (not further specified)
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

2, 4, 8, and 16 mL/kg bw, equivalent to 1900, 3800, 7600, and 15200 mg/kg bw (calculated based on a density of 0.95 g/cm³)

No. of animals per sex per dose:

4 animals (not further specified)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin irritation

Statistics:

The LD50 along with the 95% confidence limits was calculated by the moving average method based on a 14 day observation period.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

15 200 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 187.5 - <= 193 800

Remarks on result:

other: (equivalent to 16.0 ml/kg bw (95% CL 1.25 -204 ml/kg bw); calculated based on a density of 0.95 g/cm³)

Sex:

not specified

Dose descriptor:

LD0

Effect level:

1 900 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (equivalent to 2.0 ml/kg bw; calculated based on a density of 0.95 g/cm³)

Mortality:

- 16 ml/kg bw: 2/4 (both deaths occured on day 3)
- 8 ml/kg bw: 1/4 (animal died on day 11 post-dosing); repeated for confirmatory purpose: deaths 2/4 (animals died on days 2 and 3)
- 4 ml/kg bw: 1/4 (animal died on day 2 post-dosing)
- 2 ml/kg bw: 0/4

Clinical signs:

other: - 16 ml/kg bw: Erythema, oedema, necrosis, ecchymosis, fissuring, desquamation at 14 days; Prostrate at 1 day - 8 ml/kg bw: Erythema, oedema, ecchymosis, scabs at 14 days; repeated for confirmatory purpose: Oedema, necrosis at 24 h, scabs on survivors at

Gross pathology:

In victims, the lungs were red, the livers mottled bright red and tan, the kidneys were found to be mottled tan and red, the spleens appeared dark, the stomacs were injected or opaque.
In survivors, nothing remarkable was observed.

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 appropriate OECD 402 test guideline, but without GLP compliance. The test material was occlusively administered to 4 rabbits each dose group. The LD50 was determined to be 15200 mg/kg bw. The predominant clinical signs detected were signs of irritation/corrosion, such as erythema, oedema, and necrosis. No deaths occured at 1900 mg/kg bw, but still signs of skin irritation were noted. Based on this data, classification for acute dermal toxicity according to Regulation (EC) No. 1272/2008 is not warranted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

15 200 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute toxicity: oral

In the available key study (Bushy Run Research Center, 1981) the test item was tested according to a test protocol that is similar to the OECD TG 401, but without compliance with GLP. 5 male Wistar rats each group received the undiluted test material at doses of 475, 950, 1900, 3800, 7600, and 15 200 mg/kg bw via gavage. No deaths occurred and no signs of toxicity were observed at the low dose of 475 mg/kg bw. At higher doses, deaths occured and salivation, unsteady gait, diarrhoea, and sluggishness were observed. At the high dose, 3/5 animals died 30-35 min after dosing. Macroscopic evaluation revealed that in victims, the stomach was gas-filled, the glandular portions were injected, and the intestines were injected or contained blood. In survivors, nothing remarkable was observed. The LD50 was determined to be 12 825 mg/kg bw.

Acute toxicity: dermal

In the available key study (Bushy Run Research Center, 1981) the test item was tested for acute dermal toxicity according to a test protocol that is comparable to the OECD test guideline 402, but without GLP compliance. The test material was occlusively administered to 4 male New Zealand White rabbits each dose group for 24 h. The LD50 was determined to be 15 200 mg/kg bw. The predominant clinical signs detected were signs of irritation/corrosion, such as erythema, oedema, and necrosis. No deaths occurred at 1900 mg/kg bw, but still signs of skin irritation were noted.

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, 1981). In this non-guideline study, which was not compliant to GLP, the test item was tested for acute inhalation toxicity. Substantially saturated vapour did not cause any deaths or signs of toxicity in any of the male rats after 6 h of exposure. The LC50 was found to be >vapour saturation at 25°C.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.

No data are available for acute inhalation toxicity.