3-[(2,2-Dimethyl-1,2-azasilolidin-1-yl)(dimethyl)silyl]-1-propanamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Storage No.: EX0307
Chemical name: 1-[(3 -Aminopropyl)dimethyl-silyl]-2,2dimethyl- 1-aza-2-sila cyclopentane
Physical State at RT: liquid
Storage conditions: ambient, RT, protected from light
Safety precautions: Routine hygienic procedures were sufficient
to assure personnel health and safety.

Test animals

Species:

rat

Strain:

other: HsdBrl:WH Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Hsd:Wistar rats (HsdBrl:WH,Full-Barrier), Sex: male and female.
Step 1: 3 male animals were used, body weight at the commencement of the study: 166 - 183 g
Step 2: 3 female animals were used, body weight at the commencement of the study: 154 - 158 g.
Step 3: 3 male animals were used, body weight at the commencement of the study: 169 - 183 g
The animals were derived from a controlled full barrier maintained breeding system (spf).
Source: Harlan Winke1mann GmbH, D-33178 Borchen.

The animals were barrier maintained (semi-barrier) in air conditioned rooms
- Temperature: 22 ± 3° C
- ReI. humidity: 55 ± 10%
- Artificial light, lighting regime 12 : 12 hours, light 6.00 - 18.00
- Air change: 10 x / hour
- Feeding ad libitum, Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free (TPF)
- Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- The animals were kept in Macrolon cages on Altromin saw fiber bedding
- Adequate acclimatization period

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item was administered in a single dose by gavage using an intubation cannula.
Volume of application: The test item was applied according to body-weight at a volume of 10 ml/kg bw.

Doses:

The starting dose (step 1 and 2) was 200 mg/kg body weight. Since no compound-related mortality was found further testing was required.
According to OECD Guideline 423 the next step (step 3) was performed at the dose level of 2000 mg/kg body weight. According to the acute toxic
class method regime no further testing was required.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Weight Assessment
The animals were weighed prior to first application and once a week thereafter.
Clinical Examination
A careful clinical examination was made twice a day on the day of dosing and once a day thereafter.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Pathology
At the end of the observation period the animals were sacrificed by an overdosage of pentobarbital. All animals were subjected to gross necropsy. All gross pathological changes were recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 500 mg/kg bw

Based on:

test mat.

Mortality:

3 animals at a dose of 2000 mg/kg bw.

Clinical signs:

no signs observed in survivng animals

Body weight:

within normal range

Gross pathology:

no findings

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Considering the reported data of this toxicity test it can be stated that the test item has acute toxic characteristics. The LD50 was determined to be between 300 and 500 mg/kg bw.

Executive summary:

The acute toxic class method was performed with the test item. It is the principle of the acute toxic class method that, based on a stepwise procedure with the use of a minimum number of animals per step, sufficient information is obtained on the acute toxicity of the test item to enable its classification.

In the first step the test item was given in a dose of 200 mg/kg body weight to a group of 3 male rats (HsdBr1:WH Wistar) in a single

exposure via oral gavage. In a second step the test item was given in a dose of 200 mg/kg body weight to a group of 3 female rats (HsdBr1:WH Wistar) in a single exposure via oral gavage, because all male animals were still alive 24 h p. appl. without any clinical symptoms.

The dosage of 200 mg/kg bw caused no compound-related mortality neither in the three male nor in the three female animals.

A careful clinical examination was made once a day. At the end of the observation period the animals were sacrificed and necropsy was carried out to record gross pathological changes. No clinical signs of toxicity were observed throughout the observation period.

Beside acute injection ofblood vessels in the abdominal region, which is due to the euthanasia injection no special gross pathological changes were found in all animals of step 1 and step 2.

Throughout the 14-days observation period no weight loss was recorded in the animals of step 1 and 2. According to the acute toxic class method regime, in a third step the test item was given to a further group of three male animals in a dose of2000 mg/kg bw.

The dosage of 2000 mg/kg bw caused compound-related mortality in the three male animals of step 3 within 90 minutes p. appl..

Necropsy was carried out to record gross pathological changes. The following special gross pathological change was found in all animals of step 3: Mucous membrane was completely bloody.

According to the acute toxic class method regime, no further testing was required. According to the results obtained the LDso was determined to be between 300 and 500 mg/kg bw.