O,O',O''-(methylsilylidyne)trioxime 2-pentanone

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: Guideline study conducted under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

484-460-1

EC Name:

-

Cas Number:

37859-55-5

Molecular formula:

C16 H33 N3 O3 Si

IUPAC Name:

(4E,9E)-4,7,10-trimethyl-7-{[(E)-(pentan-2-ylidene)amino]oxy}-6,8-dioxa-5,9-diaza-7-silatrideca-4,9-diene

Test animals

Species:

other: Rat

Strain:

other: Wistar strain Crl:(outbred, SPF-Quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Approximately 9-12 weeks old
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the
test substance.
- Housing: Individually housed in labeled Macrolon cages (Mill type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo , S.P.P.S., Argenteuil, France) and paper as cage-enrichment 9Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF(R) Spezialdiatem GmbH, Soest, Germany)
- Water (e.g. ad libitum):ad libitum
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions. Accommodation was as described above except that the animals were group housed in labeled Macrolon cages (MIV type; height 18 cm)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 +/- 3.0°C ( actual range: 19.5-21.6°C)
- Humidity (%): 30-70% (actual range: 31-81%)
- Air changes (per hr): 15 per hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test substance was dosed undiluted as delivered by the sponsor.

MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg (2.07 ml/kg) body weight

Doses:

Frequency: Single dosage on Day 1
2000 mg/kg (2.07 mL/kg) body weight
550 mg/kg (0.569 mL/kg) body weight
175 mg/kg (0.181 mL/kg) body wieght
Dose volume calculated as dose level (g/kg)/ density (g/mL)

No. of animals per sex per dose:

Test substance was administered by oral gavage to a female Wistar rat at 2000 mg/kg body weight. In a stepwise procedure twelve additional females were dosed at 175, 550 or 2000 mg/kg body weight. The animals were dosed sequentially one at a time.

Control animals:

no

Details on study design:

- Frequency of observations and weighing: Observations: Twice daily. Weighing: Days 1 (pre-administration), 8 and 15. - Necropsy of survivors performed: Yes - Other examinations performed: Clinical Signs- At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded: Maximum grade 3: grading slight (1) to severe (3). Maximum grade 1: presence is scored (1) Necropsy- The animals surviving to the end of the observation period were sacrificed by oxygen/carbondioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded. Organ Weights- The weight from the liver, kidneys and spleen were recorded from all animals that were necropsied after 21st of April 2008. These organs were also fixed in 10% buffered formalin (neutral phosphate buffered 4% formaldehyde solution) for posible further pathological investigations. Blood Sampling- As requested by sponsor, a blood sample was collected from aminal 13 (550 mg/kg) under iso-flurane 24 hrs post treatment. The sample was drawn from the retro-orbital sinus and collected into a tube prepared with EDTA for haematological parameters (0.5 mL)

Statistics:

The LD50 was estimated based on maximum likelihood by means of the AOT425StatPGM

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 234 mg/kg bw

Mortality:

Female: 2000 mg/kg bw; Number of animals: 7; Number of deaths: 5 Female: 550 mg/kg bw; Number of animals: 5; Number of deaths: 0 Female: 175 mg/kg bw; Number of animals: 1; Number of deaths: 0

Clinical signs:

Signs of toxicity related to dose levels: The decedents and moribund animal were found on the day of treatment (Day 1). Clinical signs observed during the study period were as follows: 175 mg/kg: Hunched posture 550 mg/kg: Lethargy, hunched posture, uncoordinated movements, flat posture, slow breathing, shallow respiration, piloerection, hypothermia 2000 mg/kg: Lethargy, hunched posture, uncoordinated movements, flat posture, slow breathing, shallow and laboured respiration, piloerection, watery discharge eye, ptosis, salivation The surviving animals had recovered from the symptoms between Days 2 and 5.

Body weight:

The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated
animals of the same age and strain.

Gross pathology:

Effects on organs: The weights of the liver and kidneys animal 13 (550 mg/kg) and the liver, kidneys and spleen of animals 14 (2000 mg/kg) were within the normal
range. The weight of the spleen of animal 13 (550 mg/kg) was 0.306 and just below the normal range (0.40 - 0.69 grams). No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The Oral LD50 value of the test substance was estimated to be approximately 1234 mg/kg and was found to be within the range of 300-2000 mg/kg body weight.