Methyl-tris acetonoximo-silane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-10-31 to 2012-12-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-propanone, 2,2’,2”-[O,O’,O”-(ethylsilylidyne)trioxime]

EC Number:

611-631-1

Cas Number:

58190-57-1

IUPAC Name:

2-propanone, 2,2’,2”-[O,O’,O”-(ethylsilylidyne)trioxime]

Specific details on test material used for the study:

- Name: EAC3
- Chemical name: 2-propanone, 2,2’,2”-[O,O’,O”-(ethylsilylidyne)trioxime]
- CAS No.: 58190-57-1
- Batch/Lot Number: 1000061820
- Molecular weight: 273.404
- Manufacture date: 11 January 2010
- Expiry date: 11 January 2013
- Purity: 92.13%
- Description: Yellowish liquid
- Storage conditions: Room temperature (15-25 °C, below 70 RH%), protected from humidity
- Safety precautions: Routine safety precautions (gloves, goggles, face mask, lab coat) for unknown materials were applied to assure personnel health and safety.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test item was freshly formulated at a concentration of 250 mg/mL in the vehicle on the day of administration. The formulation container was stirred continiously up to finsihing the treatment.

Test animals

Species:

rat

Strain:

other: CRL:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Young healthy adult rats, 10-11 weeks old
- Weight at study initiation: 230 – 240 g
- Fasting period before study: night before the treatment
- Housing: 3 animals / cage
- Diet (e.g. ad libitum): Yes, ssniff SM R/M "Autoclavable complete diet for rats and mice - breeding and maintenance"
- Water (e.g. ad libitum): Yes, tap water
- Acclimation period: at least 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 22.5
- Humidity (%): 37 – 69
- Air changes (per hr): 15 – 20
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

VEHICLE
- Lot/batch no. (if required): BCBH2687V
- Expiry date: 31 December 2013

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A limit of 2500 mg/kg bw dose was required by the Sponsor. The limit dose for this study was >2000 mg/kg bw.
Initially, three females (Group 1) were treated at a dose level of 2500 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group, therefore no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris.

Doses:

2500 mg/kg bw

No. of animals per sex per dose:

3 females per step / two steps in total

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Frequency of weighing: The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly after.
- Necropsy: Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Statistics:

n.a.

Results and discussion

Preliminary study:

n.a.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

EAC3 did not cause mortality at a dose level of 2500 mg/kg bw.

Clinical signs:

other: Treatment with EAC3 at the dose level of 2500 mg/kg bw caused decreased activity (6/6), hunched back (6/6), prone position (4/6), incoordination (6/6), piloerection (5/6) and creeping gait (3/6). All animals were symptom free from three days after the tre

Gross pathology:

No macroscopic observations were present at a dose level of 2500 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in rats conducted according to OECD 423 no mortality occurred at the high dose of 2500 mg/kg bw. Hence, the LD50 value was determined to be greater than 2500 mg/kg bw.

Executive summary:

In an acute oral toxicity study (acute toxic class method, OECD 423), two groups of fasted, 10-11 weeks old, female Wistar rats (3 rats/group) were given a single oral dose of the test item (92.13% purity) in PEG 400 at the dose of 2500 mg/kg bw and were observed for 14 days. All animals survived until the end of the study showing only mild signs of toxicity. The most relevant clinical findings were decreased activity (6/6), hunched back (6/6), prone position (4/6), incoordination (6/6), piloerection (5/6) and creeping gait (3/6). All animals were symptom free from three days after the treatment.

Throughout the 14-day observation period, the body weight showed no indication of a test item-related effect. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step. Based on the results from this study, the oral LD50 in rats is considered to exceed 2500 mg/kg bw.