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

Toxicity to reproduction

Administrative data

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.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

other: Read-across

Title:

Unnamed

Year:

2013

Materials and methods

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

Test material

Test material information

Constituent 1

Reference substance name:

Butanone oxime

EC Number:

202-496-6

EC Name:

Butanone oxime

Cas Number:

96-29-7

Molecular formula:

C4H9NO

IUPAC Name:

butan-2-one oxime

Details on test material:

- Name of test material (as cited in study report): Methylethyl Ketoxyme (2-butanone oxime; MEKO)
- Molecular formula (if other than submission substance): C4H9NO
- Molecular weight (if other than submission substance): 87.12
- Smiles notation (if other than submission substance): CC(CC)=NO
- InChl (if other than submission substance): 1/C4H9NO/c1-3-4(2)5-6/h6H,3H2,1-2H3
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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 / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Details on results (P0)

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

Effect levels (P0)

1

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)

2

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)

Results: F1 generation

General toxicity (F1)

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

Details on results (F1)

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.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.