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

Endpoint summary

Description of key information

Acute oral toxicity: Key study: Test according to OECD guideline 425. GLP study. LD50 was determined to be >2000 mg/kg bw.

Acute dermal toxicity: Key study: Test method according to OECD 402. GLP study. LD50 was determined to be > 2009 mg/kg bw.

Acute inhalation toxicity: Data waiving (other justification): According to REACH Annex VIII, column 2, the study was not needed to be performed since the choice for the second route in addition for the oral route was provided for dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 Oct 2007 - 25 Jan 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 2001

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Labs, Shaver Road, Portage, MI, USA
- Age at study initiation: 8 wk
- Weight at study initiation: 206-284 g
- Fasting period before study: overnight
- Housing: 1/suspended wire mesh cage
- Diet: LabDiet 5002, Certified Rodent Diet (PMI nutrition International), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.95-23.63
- Humidity (%): 43-58
- Air changes (per hr): 12.5
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2007-10-8 To: 2007-10-29

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: < 10 ml/kg bw

- Rationale for the selection of the starting dose: lower than LD50 for closely related material

Doses:

550, 2000 mg/kg bw

No. of animals per sex per dose:

550 mg/kg bw: 1 male; 2000 mg/kg bw: 3 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality/viability: twice daily (once daily on weekends and holidays); weight: prior to dosing and weekly thereafter
- Necropsy of survivors performed: yes
- Clinical observations: 20-40 min after dosing, 3-4 h after dosing, and daily thereafter

Statistics:

none applied for determination of LD50

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths.

Mortality:

none

Clinical signs:

other: 2000 mg/kg bw: Two of three rats showed transient adverse effects including absence of or decreased activity, increased lacrimation, partially closed eye lids bilaterally, irregular respiration, red soiling of the muzzle or urogenital staining. These effe

Gross pathology:

One animal at 2000 mg/kg bw had a small focus on the left lateral liver lobe.

Other findings:

None.

One male rat was given a single dose of 550 mg/kg bw of the test substance by oral gavage. The animal showed no adverse effects within 3 days of dosing and appeared healthy. A second fastened male was dosed with 2000 mg/kg bw and also showed no adverse effects within 3 days of dosing and appeared healthy. A third male rat was dosed with 2000 mg/kg bw and showed adverse effects which were fully reversible within 3 days. Another rat was dosed with 2000 mg/kg bw and also showed adverse effects, which were reversible within 3 days.

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

A reliable acute oral toxicity study conducted in compliance with a standard guideline and GLP (reliability score 1), identified an LD50 in excess of 2000 mg/kg bw in male rats.

Executive summary:

An acute oral toxicity test was performed according to OECD 425 and GLP on butan-2-one O,O',O''-(vinylsilanetriyl)oxime. No mortality was observed and the LD50 was determined to be >2000 mg/kg bw in rats.Two of three rats showed transient adverse clinical signs which were no longer evident on day 3.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 001 mg/kg bw

Quality of whole database:

The key study is a GLP compliant and has Klimisch score 1. The quality of the database was determined as appropriate for assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided. This information is provided for dermal route.

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 Nov 1986 - 26 Nov 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Crédo, FRANCE
- Age at study initiation: 5-7 wk
- Weight at study initiation: (mean, g) 196 (m) 178 (f)
- Fasting period before study: no data
- Housing: 1/stainless steel mesh cage
- Diet: rat pelleted complete maintenance diet (U.A.R. formula "A.04), ad libitum
- Water: drinking water ad libitum
- Acclimation period: 1 wk

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

IN-LIFE DATES: (initial and main study) from: 1986-11-06 To: 1986-11-26

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10%
- Type of wrap if used: perforated bandage on gauze bandage

REMOVAL OF TEST SUBSTANCE
- Washing: wiped at end of exposure with gauze
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2.05 ml/kg bw

Duration of exposure:

24 h

Doses:

pre-study: 1000, 2009 mg/kg bw
main study: 2009 mg/kg bw

No. of animals per sex per dose:

Pre-study: 2
Main study: 5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations at 0, 1, 2, 4 h, then daily for 14 days; weighing weekly
- Necropsy of survivors performed: yes

Statistics:

Bliss
Litchfield & Wilcoxon

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 009 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

No treatment-related effects were observed.

Other findings:

No local erythema and oedema were observed.

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

A reliable dermal acute limit study conducted in compliance with a standard guideline and in accordance with GLP (reliability score 1), identified an LD50 > 2009 mg/kg bw in male and female rats. No local effects were reported.

Executive summary:

A limit study conducted in compliance with OECD 402 and in accordance with GLP, butan-2-one O,O',O''-(vinylsilanetriyl)oxime identified a LD50 for of > 2009 mg/kg bw in male and female rats. No effects were reported.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 009 mg/kg bw

Quality of whole database:

The study is a GLP compliant and has Klimisch score 1. The quality of the database was determined as appropriate for assessment.

Additional information

Acute oral toxicity:

Key study: An acute oral toxicity test was performed according to OECD 425 and GLP on butan-2-one O,O',O''-(vinylsilanetriyl)oxime. No mortality was observed and the LD50 was determined to be >2000 mg/kg bw in rats. Two of three rats showed transient adverse clinical signs which were no longer evident on day 3.

Acute dermal toxicity:

Key study: A limit study conducted in compliance with OECD 402 and in accordance with GLP, butan-2-one O,O',O''-(vinylsilanetriyl)oxime identified a LD50 for of > 2009 mg/kg bw in male and female rats. No effects were reported.

Acute inhalation toxicity:

Data waiving (other justification): According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided. This information is provided for dermal route.

Justification for selection of acute toxicity – oral endpoint

The study with highest reliability.

Justification for selection of acute toxicity – inhalation endpoint

According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided. This information is provided for dermal route.

Justification for selection of acute toxicity – dermal endpoint

Only one study available.

Justification for classification or non-classification

Based on the available data on oral and dermal acute toxicity (LD50 > 2000 mg/kg bw), butan-2 -one O,O',O''-(vinylsilanetriyl)oxime is not classified for acute toxicity according to CLP Regulation (EC) No 1272/2008.