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

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

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 similar to OECD Guideline 408, GLP study) on an analogue substance.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

96-26-7

IUPAC Name:

96-26-7

Constituent 2

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): Methyl ethyl ketoxime
- 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 of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

Based on experimental results obtained with the analogue substance butanone oxime in rats after 13 weeks oral administration where the NOAEL for erythrotoxicity was 312 ppm and the NOAEL for olfactory epithelium degeneration was 1250 ppm, the read-across approach was applied and the NOAEL for the 2-butanone-O,O',O''-(phenylsilylidyne)trioxime was estimated to be 433.93 ppm for erythrotoxicity and 1738.50 ppm for olfactory epithelium degeneration.

Effect levels

1

Dose descriptor:

NOAEL

Remarks:

(erythrotoxicity)

Effect level:

433.93 ppm

Based on:

test mat.

Remarks:

(analogue subtance)

Sex:

male/female

Basis for effect level:

other: (based on read-across approach from experimental data on analogue butanone oxime) (basis for effect: anemia)

2

Dose descriptor:

NOAEL

Remarks:

(nose)

Effect level:

1 738.5 ppm

Based on:

test mat.

Remarks:

(analogue substance)

Sex:

male/female

Basis for effect level:

other: (based on read-across approach from experimental data on analogue butatone oxime) (basis for effect: olfactory epithelium degeneration)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The concentrations used in the study on the analogue substance and the read-across approch estimation are as follows:

Unit	Sex	MEKO	POS
ppm rats	Male/female	312,00	433,93
		625,00	869,25
		1250,00	1738,50
		2500,00	3477,00
		5000,00	6954,01
mg/kg bw/day	Male	25,00	34,77
		50,00	69,54
		100,00	139,08
		175,00	243,39
		280,00	389,42
mg/kg bw/day	Female	30,00	41,72
		65,00	90,40
		120,00	166,90
		215,00	299,02
		335,00	465,92

Meko = Butanone oxime

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

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 NOAEL for 2-butanone-O,O',O''-(phenylsilylidyne)trioxime for 13 weeks repeated dose toxicity by oral route in rats was estimated to be 433.93 ppm (34.77 and 41.72 mg/kg bw/day for males and females respectively) for erythrotoxicity and 1738.50 ppm (139.08 and 166.90 mg/kg bw/day for males and females respectively) for olfactory epithelium degeneration.

Executive summary:

A 90 days repeated dose toxicity test was performed on analogue substance butanone oxime in accordance with an equivalent method to OECD Guideline 408. After 13 weeks oral administration of analogue MEKO to rats up to 5000 ppm (up to 280 mg/kg bw/day in males and up to 335 mg/kg/bw/day), the NOAEL for erythrotoxicity was determined to be 312 ppm (25 and 30 mg/kg bw/day in males and females respectively) and the NOAEL for olfactory epithelium degeneration was determined to be 1250 ppm (100 and 120 mg/kg bw/day in males and females respectively). Based on these results, the read-across approach was applied and the NOAEL for 2-butanone-O,O',O''-(phenylsilylidyne)trioxime for 13 weeks repeated dose toxicity by oral route in rats was estimated to be 433.93 ppm (34.77 and 41.72 mg/kg bw/day for males and females respectively) for erythrotoxicity and 1738.50 ppm (139.08 and 166.90 mg/kg bw/day for males and females respectively) f or olfactory epithelium degeneration.