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Toxicological information

Repeated dose toxicity: oral

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Administrative data

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.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
other: Read-across
Title:
Unnamed
Year:
2012

Materials and methods

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

Test material

Constituent 1
Reference substance name:
4-methylpentan-2-one oxime
EC Number:
203-298-2
EC Name:
4-methylpentan-2-one oxime
Cas Number:
105-44-2
IUPAC Name:
4-methylpentan-2-one oxime
Details on test material:
- Name of test material (as cited in study report): Methyl isobutil ketoxime (MIBKO)
- Molecular formula (if other than submission substance): C6H13NO
- Molecular weight (if other than submission substance): 115.1735
- Smiles notation (if other than submission substance): CC(C)CC(\C)=N\O
- InChl (if other than submission substance): 1/C6H13NO/c1-5(2)4-6(3)7-8/h5,8H,4H2,1-3H3/b7-6+
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Results of examinations

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.

Effect levels

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)

Target system / organ toxicity

Critical 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 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).