Butan-2-one O,O',O''-(methylsilylidyne)trioxime

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 Mar 1986 to 22 Jan 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(No information on test substance purity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butan-2-one O,O',O''-(methylsilylidyne)trioxime

EC Number:

245-366-4

EC Name:

Butan-2-one O,O',O''-(methylsilylidyne)trioxime

Cas Number:

22984-54-9

Molecular formula:

C13H27N3O3Si

IUPAC Name:

butan-2-one O,O',O''-(methylsilanetriyl)oxime

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): SILANE 196 - Méthyltris (méthyléthylcétiminoxy) silane
- Substance type: Ketoxime
- Physical state: Liquid
- Storage condition of test material: Minimum of 19°C.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Credo,France.
- Age at study initiation: 5-7 weeks
- Weight at study initiation: Males: 158-163 g; Females: 138-151 g
- Fasting period before study: Yes
- Housing: groups of five in stainless steel mesh cages.
- Diet: Pelleted complete maintenance diet (UAR, formula "A.D4", UAR, Epinay sur Orge, France), ad libitum
- Water: Softened and filtered drinking water, ad libitum
- Acclimation period: Minimum one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03.11.1986 To: 17.12.1986

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.85 ml/kg

Doses:

1129, 1416, 1782, 2247 (two groups), 2822 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

other: yes, distilled water

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and abnormal clinical signs were noted 15 minutes after administration of the test substance, then 1, 2 and 4 hours later and then 14 day recovery period. Body weights were measured on Day -1, Day 1 (immediately before administration), Day 8 and 15.
- Necropsy of survivors performed: yes (and of animals that died).
- Other examinations performed: gross pathology.

Statistics:

The body weight of the animals was evaluated, for each group and each sex, by calculating the mean values, the standard variation and the coefficient of variation to give a statistical appreciation of the homogeneity of the data, and whenever possible, by the Student test to compare each treated group with the control group. The gradient of the mortality curve at the different dose levels enabled an LD50 to be calculated.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 463 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Method of Bliss. The report is not entirely clear, however the upper and lower limits appear to be 95% CL.

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 453 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Method of Litchfield & Wilcoxon. The report is not entirely clear, however the upper and lower limits appear to be 95% CL.

Mortality:

See Table 1.

Clinical signs:

other: See Table 1.

Gross pathology:

Discolouration of the spleen.

Any other information on results incl. tables

Table 1: Number of animals that died, time range for mortality, body weight change and overt toxicity.

Dose (mg/kg bw)	Mortality (dead/total)			Time range of deaths (days)	Overt toxicity (numbers affected, where specified in the report)
	Male	Female	Combined
0	0/0	0/0	0/10	-	-
1129	0/0	0/0	0/10	-	Prostration, lethargy, coma (2), piloerection(10), ptosis(4), ataxia. No overt adverse effects on day 2.
1416	0/0	0/0	0/10	-	Prostration, lethargy, coma (3), piloerection(10), ptosis(5), ataxia. No overt adverse effects on day 2.
1782	2/5	0/5	2/10-	2	Prostration, lethargy, coma (6), piloerection(10), ptosis(3), ataxia. No overt adverse effects in surviving animals on day 2.
2247	2/5	2/5	4/10	2	Prostration, lethargy, coma (6), piloerection(10), ptosis(4), ataxia. No overt adverse effects on day 3.
2247	2/5	1/5	3/10	2	Prostration, lethargy, coma (7), piloerection(10). No overt adverse effects in surviving animals on day 3.
2822	4/5	3/5	7/10	2	Either prostration, lethargy or coma (8) in all animals. Some cases of piloerection, lacrimation, clonic convulsions and ataxia. No overt adverse effects in surviving animals on day 3.

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

CLP Implementation

Conclusions:

In an acute oral toxicity study conducted to the now deleted OECD 401 and to GLP (RL 1) the LD50 for butan-2-one O,O',O''-(methylsilylidyne)trioxime was 2463 mg/kg bw in rats. Clinical signs of toxicity at all doses were prostration, lethargy, ptosis, ataxia and coma in several animals. In surviving animals these signs had disappeared by day 2/3.

Executive summary:

An acute oral toxicity study was conducted according to the OECD guideline 401 under GLP conditions. Five Sprague Dawley rats per sexe were exposed to 1129, 1416, 1782, 2247 (two groups), 2822 mg/kg bw test substance by oral gavage. Control animals were administered distilled water. Mortality and abnormal clinical signs were noted 15 minutes after administration of the test substance, then 1, 2 and 4 hours later and then 14 day recovery period. Body weights were measured on Day -1, Day 1 (immediately before administration), Day 8 and 15. Necropsy was performed at day 15 to survivors and to animals which died. Clinical signs of toxicity at all doses were prostration, lethargy, ptosis, ataxia and coma in several animals. In surviving animals these signs had disappeared by day 2/3, reduced body weight gain was observed at high doses, discolouration of the spleen was observed macroscopically.  The oral LD50 was determined as 2463 mg/kg-bw/day.