Acetone oxime

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information

The substance gives negative ie non genotoxic results in a variety of different assays.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

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: The study was conducted according to generally vaiid procedures and according to GLP guidelines. All parameters described are closely related or comparable to guidline methods.

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.5385 (In Vivo Mammalian Cytogenetics Tests: Bone Marrow Chromosomal Analysis)

GLP compliance:

yes

Type of assay:

chromosome aberration assay

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc., Frederick, MD
- Age at study initiation: 6-8 weeks
- Weight at study initiation: Males, 175-200 g; Females, 138-161 g
- Assigned to test groups randomly: yes
- Housing: Housed one per cage during study in plastic autoclavable cage
- Diet (e.g. ad libitum): Certified laboratory rodent chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.2-27.7
- Humidity (%): 50 +/- 20% relative humidity
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

Distilled water
- Amount of vehicle (if gavage or dermal): dose volumes were 0.326, 0.652 and 1.304 mL/kg bw.

Duration of treatment / exposure:

Single oral dose by gavage

Frequency of treatment:

Once

Post exposure period:

6, 24 and 48 hours

Remarks:

Doses / Concentrations:
300, 600 and 1200 mg/kg bw
Basis:
nominal in water

No. of animals per sex per dose:

5/dose

Control animals:

yes, concurrent vehicle

Positive control(s):

A single oral dose of cyclophoshamide at 25 mg/kg body weight; a dose volume of 1.2 mL/kg body weight was used.

Tissues and cell types examined:

Bone marrow cells, arrested in metaphase and collected at 6, 24 and 48 hours after administration were examined microscopically for structural chromosome aberrations.

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

No statistically significant increases in percentage of aberrant cells were observed in the test article treated groups, regardless of treatment or bone marrow collection time.
Clinical signs of toxicity were noted within 4 hours of dosing at each dose level tested.

Conclusions:

Interpretation of results (migrated information): negative
Methyl ethyl ketoxime did not induce chromosomal aberrations in bone marrow cells of male or female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

The substance was negative ie non mutagenic in two reliable and one unreliable in vitro bacterial gene mutation assays. It was also negative in a reliable in vitro gene mutation assay, though no metabolic activation was used. It was also negative in four reliable in vitro unscheduled DNA repair assays conducted in V79 cells, hepatocytes and seminal vesicle cells. There is a positive result from an in vivo SMART assay however this study is considered unreliable. There are also two unreliable, non-standard studies which examined effects on nucleoside modification.

 

These results are broadly consistent with those found for the read-across candidate butanone oxime (CAS 96-29-7), which gave negative results in two reliable in vitro bacterial gene mutation assays and a reliable in vitro unscheduled DNA repair assay in hepatocytes. It gave a positive result in an in vitro mammalian gene mutation assay however this was in the presence of high levels of cytotoxicity. Butanone oxime also gave negative results in a reliable in vivo cytogenetics assay.

 

Overall, in genotoxicity studies for a variety of endpoints, both acetone oxime and butanone oxime gave a similar negative pattern of results.

Justification for selection of genetic toxicity endpoint
This is the only reliable in vivo study.

Justification for classification or non-classification

The substance gives negative results in a number of in vitro gentoxicity assays. This is also supported by a negative result from a reliable in vivo study on a read-across substance. Therefore there is no requirement for classification.