2-Propanone, 2,2',2''-[O,O',O''-(ethylsilylidyne)trioxime]

Endpoint summary

Description of key information

Key study: Based on the read-across from experimental results on the analogue substance Wasox-VMAC2 (OECD Guideline 407, GLP study), the NOEL of EAC3 for 28 days oral exposure in rats was estimated to be 15.99 mg/kg bw/day.
Key study: Based on the read-across from experimental results on the analogue substance Wasox-MMAC2 (OECD Guideline 407, GLP study), the NOEL of EAC3 for 28 days oral exposure in rats was estimated to be 16.54 mg/kg bw/day.
Key study: Based on the read-across from experimental results on the analogue substance MIBKO (OECD Guideline 408, GLP study), the NOAEL of EAC3 for 90 days oral exposure in rats was estimated to be 11.87 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose 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:

EAC3 undergoes rapid hydrolysis in aqueous to acetone oxime and the corresponding ethylsilanetriol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetone oxime and their values are comparable. Moreover, the analogue methyl isobutyl ketoxime, which shares the same functional groups with acetone oxime, also has comparable values for the relevant molecular properties and they are toxicologically equivalent.

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 OECD Guideline 408, GLP study) on the analogue substance MIBKO

GLP compliance:

no

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

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

no effects observed

Ophthalmological findings:

no effects observed

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

Based on the experimental results obtained in the analogue substance MIBKO, where the NOAEL for 90 days oral exposure in male and female rats was determined to be 15 mg/kg bw/day based on the effects on red blood cells, resulting in associated changes in the spleen), the read-across approach was applied and the NOAEL (90 days, oral) for EAC3 in rats was estimated to be 11.87 mg/kg bw/day in rats.

Dose descriptor:

NOEL

Effect level:

11.87 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: (Read-across approach from an analogue substance) (Basis for effect: effects on red blood cells, resulting in associated changes in the spleen)

Critical effects observed:

not specified

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

Conclusions:

Based on the read-across approach from experimental data on analogue substance MIBKO (OECD Guideline 408, GLP study), the NOAEL of EAC3 for 90 days oral exposure in rats was determined to be 11.87 mg/kg bw/day.

Executive summary:

A 90 days oral repeated dose toxicity test was performed on the analogue substance MIBKO according to OECD Guideline 407 and GLP. The NOAEL was determined to be 15 mg/kg bw/day in rats based on the effects on red blood cells, resulting in associated changes in the spleen were observed at 50 mg/kg bw/day. Based on these results, the read-across was applied and the NOAEL of EAC3 for 90 days oral exposure in rats was estimated to be 11.87 mg/kg bw/day under the test conditions (effects at an estimated concentration of 39.57 mg/kg bw/day).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

11.87 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

One 90 day and two 28 day exposure duration studies performed on an analogue substance, GLP compliant and Klimisch score = 2.The overall quality of the database was determined as appropriate for assessment.

Additional information

Key study: Read-across approach from experimental results on the analogue substance Wasox-VMAC2:

A repeated dose 28 -day oral toxicity study in rodents for the analogue substance Wasox-VMAC2 was performed in accordance with OECD Guideline 407 and GLP. The test material was administered groups of 5 rats per sex and dose, once a day for 28 consecutive days. The dose used were 0 (control) 20, 63, and 200 mg/kg/day, including satellites groups of the control and the highest dose with a 14 days observation period to analyse reversibility or persistence of test substance induced lesions. The effects noted at a dose of 200 mg/kg and below were mainly adaptations to damage to peripheral erythrocytes without an impairment of the blood cell production in the bone marrow. The NOEL was determined to be 20 mg/kg bw/day. Based on these results the read-across approach was applied and the NOEL of EAC3 for 28 days oral exposure in rats was estimated to be 15.99 mg/kg bw/day.

Key study: Read-across approach from experimental results on the analogue substance Wasox-MMAC2:

A repeated dose 28 -day oral toxicity study in rats was performed on the analogue substance Wasox-MMAC2 according to OECD Guideline 407 and GLP. The test material was administered by by gavage to 5 rats per sex and per group once a day for 28 consecutive days at a concentration of 0 (control) 20, 63, and 200 mg/kg/day. Reversibility or persistence was analysed by 2 groups of 5 males and 5 females each (high dose satellite group and control satellite group) for further 14 days without test substance administration. The NOEL was determined to be 20 mg/kg bw/day for both sexes since damages to mature erythrocytes in the peripheral blood, with a parallel marked increase production of your erythrocytes by the presence of hematopoiesis in the spleen was observed in higher doses. Based on these results, the read-across approach was applied and the NOEL of EAC3 for 28 days oral exposure in rats was estimated to be 16.54 mg/kg bw/day.

Key study: Read-across approach from experimental results on the analogue substance MIBKO:

A repeated dose 90 -day oral toxicity study in rats was performed on the analogue substance MIBKO according to OECD Guideline 408 and GLP. 4 groups each comprising 10 rats per sex were exposed to 0 (control) 5, 15 or 50 mg/kg/day. A further five male and five female were assigned to each of the groups which were treated for 13 weeks, followed by a 4 week period without treatment for recovery assessment. The principal action of MIBKO was to affect the red blood cell rate of turnover occurring mainly among animals receiving 50 mg/kg/day, resulting in associated changes in the spleen. A dosage level of 15 mg/kg/day, was considered to be the NOAEL for MIBKO in both sexes, as the changes observed at 5 and 15 mg/kg/day were considered to be minor in nature and had shown full recovery after 4 weeks without treatment. Based on these results, the read-across approach was applied and the NOAEL of EAC3 for 90 days oral exposure in rats was estimated to be 11.87 mg/kg bw/day.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The study with the longest duration (90-days) was chosen (key study).

Justification for classification or non-classification

Based on the available data on a 90-day study, oral administration of the test material to rats affected the red blood cell turnover resulting in associated changes in the spleen at an estimated dose level of 39.57 mg/kg bw/day. Taking into account this information, the substance would be classified as STOT RE Category 2 (Specific target organ toxicity — repeated exposure) according to CLP Regulation (EC) nº 1272/2008.