N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

Use of 200 mg/kg bw instead of 300 mg/kg bw

Principles of method if other than guideline:

Draft report, GLP etc not signed off. Doses of 2000 and 200 mg/kg bw, current guideline indicates 2000 and 300 mg/kg bw.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine

EC Number:

221-336-6

EC Name:

N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine

Cas Number:

3069-29-2

Molecular formula:

C8H22N2O2Si

IUPAC Name:

N-[3-[dimethoxy(methyl)silyl]propyl]ethane-1,2-diamine

Constituent 2

Reference substance name:

N-[3-(dimethoxymethylsilyl)propyl]ethylnenediamine

IUPAC Name:

N-[3-(dimethoxymethylsilyl)propyl]ethylnenediamine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, UK
- Age at study initiation: 5 to 7 weeks
- Weight at study initiation: 97 to 135 g
- Fasting period before study: overnight
- Housing: metal cages with wire mesh floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25.5
- Humidity (%): 38-60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 or 20% w/v in 1% w/v aqueous methylcellulose


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

2000 mg/kg, 200 mg/kg

No. of animals per sex per dose:

3 females at 2000 and 200 mg/kg, 3 males at 200 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed twice a day, and weighed on days 1, 8 and 15 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All animals were subjected to a macroscopic examination which consisted of opening the cranial thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

200 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All females dosed at 2000 mg/kg died within approximately 2 hours of dosing. Macroscopic examination of these animals revealed congestion in the subcutaneous tissue, brain, heart, liver, spleen and kidneys. Congestion with gaseous distension and fluid contents were also noted in the stomach and along the alimentary tract.

Clinical signs:

other: Piloerection was observed in all rats soon after dosing. This sign persisted and was accompanied during the study by hunched posture (all females at 200 mg/kg and one female at 2000 mg/kg) waddling/unsteady gait, lethargy, abnormal respiration (characteri

Gross pathology:

No macroscopic abnormalities were recorded for the animals killed and examined at study termination on day 15.

Other findings:

None reported.

Any other information on results incl. tables

A group of three fasted rats received a single oral gavage dose of the test substance, formulated in 1% w/v aqueous methylcellulose, at a dose level of 2000 mg/kg bodyweight. As a result of mortalities at this dosage indicating the acute lethal oral dose of the test material to be less than 2000 mg/kg bw, in compliance with the study guidelines a further group of three fasted females was dosed at 200 mg/kg. A group of three fasted males was then dosed at 200 mg/kg to confirm results at this dosage and complete the study.

All females dosed at 2000 mg/kg died within ca. 2 hours of dosing. Macroscopic examination of decedents revealed a generalised congestion in the majority of organs and tissues. Clinical signs of reaction to treatment included piloerection, seen in all rats at both dosages. In addition, hunched posture, waddling/unsteady gait, lethargy, abnormal respiration, partially closed eyelids, pallid extremities, abnormal faeces, ungroomed appearance, prostration, blue/cold extremities and dark colouring to eyes were seen in one or more animals during the study. Recovery of surviving rats at 200 mg/kg dose, as judged by external behaviour, was complete by day 7. All surviving animals were considered to have achieved satisfactory bodyweight gains throughout the study. No macroscopic abnormalities were recorded for the animals killed and examined at study termination on day 15.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 value of 200 - 2000 mg/kg bw was reported in a reliable study carried out in accordance with OECD Test Guideline 423 and in compliance with GLP