N-[3-(methoxydimethylsilyl)propyl]ethylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 June 2002 to 05 Mar 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Freie und Hansestadt Hamburg, Behörde für Arbeit, Gesundheit uns Soziales, Germany

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(methoxydimethylsilyl)propyl]ethylenediamine

EC Number:

221-337-1

EC Name:

N-[3-(methoxydimethylsilyl)propyl]ethylenediamine

Cas Number:

3069-33-8

Molecular formula:

C8H22N2OSi

IUPAC Name:

(2-aminoethyl)[3-(methoxydimethylsilyl)propyl]amine

Details on test material:

- Name of test material (as cited in study report): VP 50991
- Physical state: colourless liquid
- Stability under test conditions: > 1 day (4°C, in the dark) if vehicle is free of water
- Storage condition of test material: at room temperature, dry, tightly closed, dark

Test animals

Species:

rat

Strain:

other: Crl:CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld, Germany
- Age at study initiation: 41 (males) or 48 (females) days
- Weight at study initiation: 202 - 229 g (males); 171 - 182 g (females)
- Fasting period before study: yes (16 h before administration)
- Housing: 2-3 animals per cage during the 14-day observation period (MAKROLON cages, type III)
- Diet: ssniff/R/M-H V 1530 (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55± 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 June 2002 To: 22 Aug 2002

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

used only for 200 mg/kg bw dose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 90.91 mg/ml
- Amount of vehicle (if gavage): 2.2 ml

MAXIMUM DOSE VOLUME APPLIED: 2.2 ml

Doses:

200 and 2000 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw: 3 males
200 mg/kg bw: 3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, at 5, 15, 30 and 60 min, as well as at 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days (once daily). Body weight was determined before administration and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: Changes of skin and fur, eyes and mucous membranes, respiratory and circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern were observed at least once daily until all symptoms subsided (afterwards each working day).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

200 mg/kg bw: 0/3 males and 0/3 females died
2000 mg/kg bw: 2/3 males died within 2 days

Clinical signs:

2000 mg/kg bw: reduced motility, ataxia, reduced muscle tone, and dyspnoea
200 mg/kg bw: no signs of toxicity were observed

Body weight:

All surviving animals gained the expected body weight.

Gross pathology:

No abnormalities were observed.

Any other information on results incl. tables

Table 1: Body weights of the surviving rats.

Body weights (g)	2000 mg/kg bw	200 mg/kg bw
	male	male	female
start	221.0	203.3	176
after 7 days	278.0 ± 26.4	269 ± 32.6	200.3 ± 14.1
after 14 days	319.0 ± 45.0	302.7 ± 48.9	222.0 ± 26.2

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute oral toxicity study conducted according to OECD 423 and in compliance with GLP, a LD50 cut-off value of 1000 mg/kg bw was observed in rats. Mortality was observed in the high dose group (2/3 males died within 2 days), whereas no mortality occurred in the 200 mg/kg bw dose group (0/3 males and 0/3 females). Clinical signs of toxicity at 2000 mg/kg bw were reduced motility, ataxia, reduced muscle tone, and dyspnoea. In surviving animals no clinical signs were observed.