1,1,1-triethoxy-N,N-diethylsilanamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10th October 2002 - 04 November 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

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)

Deviations:

yes

Remarks:

The sequence of dosing may not always follow the Test Guideline as shown in the schematic diagram in attachment 1. It is Company Policy to minimise the number of animals used on each study in accordance with UK Government Home Office guidelines.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

diethyl(triethoxysilyl)amine

EC Number:

700-051-5

Cas Number:

35077-00-0

Molecular formula:

C10H25NO3Si

IUPAC Name:

diethyl(triethoxysilyl)amine

Details on test material:

- Name of test material (as cited in study report): DEATES

The client has requested that the test material name be amended due to differences between the protocol and the test material data sheet.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK

- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age.

- Weight at study initiation: Weights not recorded, however, the bodyweights fell within an interval of +/- 20% of the mean initial bodyweight of the first group.

- Fasting period before study: Overnight fasting immediately before dosing and for approximately three to four hours after dosing.

- Housing: The animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.

- Diet (e.g. ad libitum): Certified Rat and Mouse Diet (Code 5LF2) supplied by International Products Supplies Limited, Wellingborough, Northants, UK. The diet was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

- Water (e.g. ad libitum): Free access to mains drinking water. The water was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 19 deg C to 25 deg C.

- Humidity (%): Set to achieve limits of 30 to 70%.

- Air changes (per hr): The rate of air exchanges was at least fifteen changes per hour.

- Photoperiod (hrs dark / hrs light): Light controlled by a time switch to give twelve hours continuous light (06:00 to 18:00 and twelve hours darkness.

IN-LIFE DATES: From: 10th October 2002 To: 24th October 2002

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The substance was present at levels of 30 mg/ml in the vehicle.

- Amount of vehicle (if gavage): Test material was made into a solution with the vehicle at a dose level of 300 mg/kg.

- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve in distilled water.

- Lot/batch no. (if required): Not recorded.

- Purity: Not recorded.


MAXIMUM DOSE VOLUME APPLIED:
10 ml/kg

The test material was administered orally undiluted at a dose level of 2000 mg/kg, and as a solution in arachis oil BP at a dose level of 300 mg/kg.

Dosing was performed sequentially.

DOSAGE PREPARATION (if unusual):
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

Doses:

300 (with vehicle) and 2000 (undiluted) mg/kg.

No. of animals per sex per dose:

3 animals per dose, 3 dose groups.

Control animals:

no

Details on study design:

- Duration of observation period following administration:
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2, and 4 hours after dosing and subsequently once daily for up to fourteen days.

- Frequency of observations and weighing:
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, necropsy.

Statistics:

None recorded.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 500 - < 1 000 mg/kg bw

Mortality:

Individual mortality data are given in Attachment 2 - Table 1.

Two animals treated with 2000 mg/kg were found dead one day after dosing. There were no deaths noted at a dose level of 300 mg/kg,

Clinical signs:

other: Individual clinical observations are given in Attachment 2 - Table 2 and Table 3. Signs of systemic toxicty noted in animals treated with 2000 mg/kg were hunched posture, lethargy, ataxia, decreased respiratory rate, diarrhoea, ptosis and pilo-erection.

Gross pathology:

Individual necropsy findings are given in Attachment 2 Table 6 and Table 7.

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys, haemorrhage of the gastric mucosa, non-glandular epithelium of the stomach and small intestine. Stomach adhering to the liver was noted in the animal treated with 2000 mg/kg that was killed at the end of the study. No abnormalities were noted at necropsy of animals treated with 300 mg/kg.

Other findings:

No other findings recorded.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 500 - 1000 mg/kg bodyweight.

Executive summary:

In an acute oral toxicity study, groups of 8-12 week old, Sprague-Dawley CD (Crl: CD (SD) IGS BR) stain rat (3 females per dose group) were given a single oral dose of U-donor in arachis oil BP at doses of 300 mg/kg bw and undiluted at doses of 2000 mg/kg bw and observed for 14 days.

Oral LD₅₀Females = 500-1000 mg/kg bw

 

U-donor is of MODERATE Toxicity based on the LD₅₀ in females. The test material was classified as HARMFUL and the symbol “Xn” and risk phrase R22 “HARMFUL IF SWALLOWED” are required according to EU labelling regulations Commission Directive 2001/59/EC.