Bis(trimethoxysilylpropyl)amine

Acute Toxicity: dermal

Administrative data

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.

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 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

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:

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

Administration / exposure

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.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

16 mL/kg bw

Based on:

test mat.

95% CL:

8.43 - 30.6

Effect levels 2

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

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

11.3 mL/kg bw

Based on:

test mat.

95% CL:

5.09 - 25.2

Effect levels 4

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

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 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.