Bis(trimethoxysilylpropyl)amine

Acute Toxicity: oral

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Bis(trimethoxysilylpropyl)amine

EC Number:

280-084-5

EC Name:

Bis(trimethoxysilylpropyl)amine

Cas Number:

82985-35-1

Molecular formula:

C12H31NO6Si2

IUPAC Name:

3,3,11,11-tetramethoxy-2,12-dioxa-7-aza-3,11-disilatridecane

Details on test material:

- Name of test material (as cited in study report): Organofunctional Silane Y-9492
- Physical state: clear, non-viscous liquid
- Lot/batch No.: 09989
- Identification: NB 2225-99
- BRRC Sample No.: 44-365
- Date of Receipt: 15 December 1981

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

Effect levels 1

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)

Effect levels 2

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

Effect levels 3

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)

Effect levels 4

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.

Applicant's summary and conclusion

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.