2-butanone-O,O',O''-(phenylsilylidyne)trioxime

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: Test method according to EPA OTS 798, similar to OECD 401. GLP study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

433-360-6

EC Name:

-

Cas Number:

34036-80-1

Molecular formula:

C18H29N3O3Si

IUPAC Name:

6-{[(butan-2-ylidene)amino]oxy}-3,9-dimethyl-6-phenyl-5,7-dioxa-4,8-diaza-6-silaundeca-3,8-diene

Constituent 2

Reference substance name:

2-butanone-O,O',O''- (phenylsilylidyne)trioxime

IUPAC Name:

2-butanone-O,O',O''- (phenylsilylidyne)trioxime

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): OS-9000
- Physical state: Light yellow liquid
- Expire date: May 14, 1998

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River Laboratories, Inc., Portage, Michigan.
- Age at study initiation: young adult
- Weight at study initiation: 200-300g
- Fasting period before study: overnight
- Housing: The animals were housed individually in suspended stainless steel cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21.5-23.5 ºC (71-74ºF)
- Humidity: 39-53 %
- Air changes (per hr): 10-15 air changes/hour
- Photoperiod: 12-hour light/l2-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.98 mL/kg

DOSAGE PREPARATION (if unusual): Individual doses were calculated based on the animal's fasted (day 0) body weight.

RATIONALE FOR DOSE SELECTION: A range findint study was performed exposing one rat per sex per dose to 100, 500, 1000, 2000 and 3000 mg/Kg. Clinical observation, body weights and gross necropsy were analysed. The range-finding data indicated that the test article produced mortality at the highest tested dose level of 3000 mglkg level in females, but did not produce mortality at that level in the males.

Doses:

100, 500, 2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females per dose.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: two times on study day 0 (postdose) and daily thereafter (days 1-14).
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, gross necropsy, organ weights, histopathohlogy
Organ weights: Heart, Kidneys (paired), Liver, Spleen, Testes (paired), Brain.
Retained tissues: Heart, Kidneys (paired), Liver, Spleen, Testes (paired), Brain, Femur (bone marrow), Ovaries, Thymus.

Statistics:

Since the LD50 values could not be reliably calculated based on the mortality response, the LD50 was estimated based on the observed data.
Body weights, body weight gains and organ weights were analyzed by one-way analysis of variance.

Results and discussion

Preliminary study:

A. Range-Finding Study
1. Dosing
On day -1, the animals chosen for the range-finding study were weighed and fasted overnight. On day 0, the test article was administered orally as a single dose using a ball tipped stainless steel gavage needle attached to a syringe at the following levels: 100, 500, 1000, 20000, 3000 mg/kg.
Number of animals per sex per dose: 1 male, 1 female per dose.
2. Clinical Observations
The range-finding animals were observed for mortality on day 0 (post-dose) and on days 1-7. A general healthlmortality check was performed twice daily (in the morning and in the afternoon).
3. Body Weights
Individual body weights were obtained for the range-finding animals prior to fasting (day -1) and prior to dosing on day 0.
4. Gross Necropsy
All range-finding animals which died spontaneously during the study or were euthanized by carbon dioxide inhalation at study termination (day 7) were removed from study. No necropsy was performed.
The range-finding data indicated that the test article produced mortality at the highest tested dose level of 3000 mglkg level in females, but did not produce mortality at that level in the males.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The only mortality occurred on study day 1 at 2000 mgl/kg bw.

Clinical signs:

other: The most notable clinical abnormalities observed during the study included prostration, decreased activity, wobbly gait, rigidity upon handling, breathing abnormalities, urine stain, decreased defecation, partially closed eyelids and dark material around

Gross pathology:

Gross internal findings observed in the animal that died included abnormal content in the trachea, digestive tract and urinary bladder, reddened mucosa in the small intestine, mottled lungs, stained mucosa in the stomach, and dark red foci on the thymus. Significant gross internal findings observed at necropsy on study day 14 included blackish-purple spleens in the animals dosed at 500 and 2000 mglkg. Significant gross internal findings observed at necropsy on study day 14 included blackish-purple spleens in the animals dosed at 500 and 2000 mg/kg. Statistically significant increases in spleen weight relative to final body weight were observed for males dosed at 500 and 2000 mg/kg.

Other findings:

Organ weights: Statistical differences in absolute spleen weight were observed in the males dosed at 500 mg/kg. Although not statistically different, there was also an increase for the animals dosed at 2000 mg/kg. Statistically significant increases in spleen weight relative to final body weight were observed for males dosed at 500 and 2000 mg/kg. Increases in spleen weight relative to final body weight, while greater in females dosed at 500 and 2000 mg/kg, were not statistically significant. No other statistically significant differences were observed.

Any other information on results incl. tables

Under the conditions of this test, the acute oral LD50 in the rat was determined to be greater than 2000 mgl/kg. However, toxicity was observed in rats dosed at 2000 mgkg and 500 mgl/kg as expressed by adverse clinical signs and significant body weight decreases. The 100 mgl/kg dose group was considered to be NOAEL.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of test item was determined to be greater than 2000 mg/kg. 

Executive summary:

This study was performed to assess the short-term toxicity of test item in Sprague-Dawley rats when administered by gavage as a single oral dose according to EPA OTS EPA OTS 798.1175. This study is intended to provide information on the potential health hazards of the test article with respect to oral exposure. Under the conditions of this test, the acute oral LD50 in the rat was determined to be greater than 2000 mglkg. However, toxicity was observed in rats dosed at 2000 mg/kg and 500 mg/kg as expressed by adverse clinical signs and significant body weight decreases. The 100 mg/kg dose group was considered to be NOAEL.