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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

2-butanone-O,O',O''- (phenylsilylidyne)trioxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from experimental data (test method according to EPA OTS 798.4700) on an analogue substance.

GLP compliance:

no

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Other effects:

not examined

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Based on the experimental results on the analogue where adult toxicity was observed in both generations and both sexes at all doses (LOAEL for parental toxicity = 10 mg/kg bw/day, basis for effect: hematopoiesis and hemosiderosis in spleens and livers), the read-across approach was applied and the LOAEL for parental toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rats was estimated to be 13.91 mg/kg bw/da

Dose descriptor:

LOAEL

Remarks:

(parental toxicity)

Effect level:

13.91 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

(analogue substance)

Sex:

male/female

Basis for effect level:

other: (Based on read-across approach from analogue substance butanone oxime) (Basis for effect: hematopoiesis and hemosiderosis in spleens and livers of P and F1 males and females).

Remarks on result:

other: Generation: other: (P and F1) (migrated information)

Dose descriptor:

NOAEL

Remarks:

(reproductive and postnatal toxicity)

Effect level:

> 278.16 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

(analogue substance)

Sex:

male/female

Basis for effect level:

other: (Based on read-across approach from analogue substance butanone oxime) (Basis for effect: no effects at highest dose tested).

Remarks on result:

other: Generation: (F1 and F2) (migrated information)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Based on the experimental results on the analogue where no evidence of reproductive organ or mammary gland pathology or of reproductive or postnatal toxicity was observed at the highest dose (NOAEL for reprotox > 200 mg/kg bw/day), the read-across approach was applied and the NOAEL for reproduction and postanatal toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rats was estimated to be > 278.16 mg/kg bw/day.

Reproductive effects observed:

not specified

See "Data Matrix" and "Reporting Format" attached.

Conclusions:

Based on the read-across approach from experimental results on analogue butanone oxime, the LOAEL for parental toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rats was estimated to be 13.91 mg/kg bw/day and the NOAEL for reproduction and postanatal toxicity was estimated to be > 278.16 mg/kg bw/day.

Executive summary:

A two-generation study was performed on the analogue substance butanone oxime on CD (Sprague-Dawley) rats according to EPA OTS 798.4700 up to 200 mg/kg bw/day. Based on the experimental results on the analogue where adult toxicity was observed in both generations and both sexes at all doses (LOAEL for parental toxicity = 10 mg/kg bw/day, basis for effect: hematopoiesis and hemosiderosis in spleens and livers) and where no evidence of reproductive organ or mammary gland pathology or of reproductive or postnatal toxicity was observed at the highest dose (NOAEL for reprotox > 200 mg/kg bw/day), the read-across approach was applied and the LOAEL for parental toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rats was estimated to be 13.91 mg/kg bw/day and the NOAEL for reproduction and postanatal toxicity was estimated to be > 278.16 mg/kg bw/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

278.16 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

One two-generation study is available on an analogue substance with a Klimisch score = 2. The overall quality of the database was determined as appropriate for assessment.

Additional information

Key study: Read-across from experimental results on analogue substance butanone oxime:

Key study: A two-generation study was performed on the analogue substance butanone oxime on CD (Sprague-Dawley) rats according to EPA OTS 798.4700 up to 200 mg/kg bw/day. Based on the experimental results on the analogue where adult toxicity was observed in both generations and both sexes at all doses (LOAEL for parental toxicity = 10 mg/kg bw/day, basis for effect: hematopoiesis and hemosiderosis in spleens and livers) and where no evidence of reproductive organ or mammary gland pathology or of reproductive or postnatal toxicity was observed at the highest dose (NOAEL for reprotox > 200 mg/kg bw/day), the read-across approach was applied and the LOAEL for parental toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rats was estimated to be 13.91 mg/kg bw/day and the NOAEL for reproduction and postanatal toxicity was estimated to be > 278.16 mg/kg bw/day.

Short description of key information:
Key study: Based on the read-across approach from experimental data (Test method EPA OTS 798.4700) on analogue butanone oxime, the NOAEL for reproductive and postnatal toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in a two-generation study was estimated to be > 278.16 mg/kg/day for rats.

Justification for selection of Effect on fertility via oral route:
One two-generation study available (key study).

Effects on developmental toxicity

Description of key information

Key study: Based on the read-across approach from experimental results (Test method EPA OTS 798.4900) on analogue butanone oxime where no treatment-related gestational effects, malformations or developmental variations were observed, the NOAEL for developmental toxicity of 2-butanone-O,O',O''- (phenylsilylidyne)trioxime was determined to be > 834.48 mg/kg bw/day in rats. 

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

2-butanone-O,O',O''- (phenylsilylidyne)trioxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from experimental results (test method according to EPA OTS 798.4900) on an analogue substance.

GLP compliance:

no

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Based on the experimental results on the analogue substance where the LOAEL for maternal toxicity was determined to be 60 mg/kg bw/day (basis for effect: enlarged spleens), the read-across approach was applied and the LOAEL for maternal toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rats was estimated to be 83.45 mg/kg bw/day.

Dose descriptor:

NOAEL

Effect level:

> 834.48 mg/kg bw/day (actual dose received)

Based on:

test mat.

Remarks:

(analogue substance)

Basis for effect level:

other: developmental toxicity

Dose descriptor:

LOAEL

Effect level:

83.45 mg/kg bw/day (actual dose received)

Based on:

test mat.

Remarks:

(analogue substance)

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Based on the experimental results on the analogue substance where the NOAEL for developmental toxicity was determined to be >600 mg/kg bw/day (basis for effect: no effects were observed), the read-across approach was applied and the NOAEL for developmental toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rats was estimated to be >834.48 mg/kg bw/day.

Abnormalities:

not specified

Developmental effects observed:

not specified

See "Data Matrix" and "Reporting Format" attached.

Conclusions:

Based on the read-across approach from experimental results on analogue butanone oxime, the LOAEL for maternal toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rats was estimated to be 83.45 mg/kg bw/day and the NOAEL for developmental toxicity >834.48 mg/kg bw/day.

Executive summary:

A Prenatal Developmental Toxicity Test was performed on the analogue substance butanone oxime up to 600 mg/kg bw/day in Sprague-Dawley rats according to EPA OTS 798.4900. Based on the experimental results on the analogue substance where the LOAEL for maternal toxicity was determined to be 60 mg/kg bw/day (basis for effect: enlarged spleens) and the NOAEL for developmental toxicity was determined to be >600 mg/kg bw/day (basis for effect: no effects were observed), the read-across approach was applied and the LOAEL for maternal toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime was estimated to be 83.45 mg/kg bw/day and the NOAEL for developmental toxicity >834.48 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

692.06 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Two studies available on an analogue substance for developmental toxicity with Klimisch scores = 2 and 3. The overall quality of the database was determined as appropriate for assessment.

Additional information

Read-across from experimental results on analogue substance butanone oxime:

Key study: A Prenatal Developmental Toxicity Test was performed on the analogue substance butanone oxime up to 600 mg/kg bw/day in Sprague-Dawley rats according to EPA OTS 798.4900. Based on the experimental results on the analogue substance where the LOAEL for maternal toxicity was determined to be 60 mg/kg bw/day (basis for effect: enlarged spleens) and the NOAEL for developmental toxicity was determined to be >600 mg/kg bw/day (basis for effect: no effects were observed), the read-across approach was applied and the LOAEL for maternal toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime was estimated to be 83.45 mg/kg bw/day and the NOAEL for developmental toxicity >834.48 mg/kg bw/day.

Supporting study: A Prenatal Developmental Toxicity Test was performed on the analogue substance butanone oxime up to 600 mg/kg bw/day in New Zealand White rabbits according to EPA OTS 798.4900. Based on the experimental results on the analogue substance where the NOAEL for maternal toxicity was determined to be 24 mg/kg bw/day, the read-across approach was applied and the NOAEL for maternal toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rabbits was estimated to be 33.38 mg/kg bw/day. In reference to the developmental toxicity, in the study performed on analogue butanone oxime only 6 rabbits produced litters due to an excessive maternal mortality and abortions at the 40 mg/kg dose level. The NOAEL for developmental toxicity was determined to be 24 mg/kg bw/day (basis for effect: a decrease in the mean number of viable fetuses and an increase in the number of early resorptions). Based on these results, the NOAEL for developmental toxicity for 2-butanone-O,O',O''- (phenylsilylidyne)trioxime in rabbits was estimated to be 33.38 mg/kg bw/day. Nevertheless, the severe maternal toxicity and limited number of litters precluded a full assessment of developmental toxicity.

Justification for selection of Effect on developmental toxicity: via oral route:
The study performed in rats was chosen due to its higher quality (key study).

Justification for classification or non-classification

Based on the available information on toxicity to reproduction and developmental toxicity, 2-butanone-O,O',O''- (phenylsilylidyne)trioxime was considered to be negative for toxicity to reproduction, and therefore the substance is not classified in accordance with CLP Regulation (EC) No 1272/2008.