Cyclohexanone oxime

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Equivalent to guideline with limited documentation

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

not specified

GLP compliance:

yes

Remarks:

In compliance with U.S. Food and Drug Administration Good Laboratory Practices regulations (21 CFR, Part 58)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Cyclohexanone oxime

EC Number:

202-874-0

EC Name:

Cyclohexanone oxime

Cas Number:

100-64-1

Molecular formula:

C6H11NO

IUPAC Name:

cyclohexanone oxime

Test material form:

solid: crystalline

Details on test material:

Name of test material (as cited in study report): cyclohexanone oxime
- Substance type: white crystalline solid
- Analytical purity: > 99% for both lots used
- Impurities (identity and concentrations):
- Lot/batch No.: Lots 02616LT and 08812MX
- Stability under test conditions: no degradation of cyclohexanone oxime throughout the study
- Storage condition of test material: stable in aqueous solution at a concentration of 106 ppm for 4 weeks at 5 °C when stored in a sealed container, protected from light. Solutions exposed to light in drinking water bottles were stable for 5 days. Substance stored in a sealed container at 5 °C or less, protected from light.

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS (data from repeated dose studies)
- Source: Taconic Farms (Germantown, NY, USA)
- Age at study initiation: 6 weeks
- Assigned to test groups randomly
- Housing: individually
- Diet (ad libitum): NIH-07 Open Formula Diet (Zeigler Brothers, Inc.,Gardners, PA) in pellet form
- Water (e.g. ad libitum): tap water
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 15
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil
- Concentration of test material in vehicle: 400-1000 mg/kg bw dissolved in 0.4 mL

Details on exposure:

No data

Duration of treatment / exposure:

3 injections within 3 days

Frequency of treatment:

daily

Post exposure period:

Sacrifice 24 h after last exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 400, 600, 800, 1000 mg/kg bw/day
Basis:
nominal conc.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide

- Route of administration: i.p.
- Doses / concentrations: 25 mg/kg

Examinations

Tissues and cell types examined:

Polychromatic erythrocytes from femur bone marrow

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION: Air-dried smears were fixed and stained (no further details)

METHOD OF ANALYSIS: 2000 polychromatic erythrocytes were scored from in each animal

Evaluation criteria:

A trial was considered positive when p-value of trend test was <= 0.025 or a single result had a p-value <= 0.025, divided by number of exposure groups
The final call of a positive result was determined considering the results of statistical analysis, reproducibility and magnitude of effects

Statistics:

The one-tailed Cochran-Armitage test was used to analyse trends over exposure groups. Excess binominal variation was tested with a binominal dispersion test and if positive, the Cochran-Armitage test was adjusted upwards in proportion to the excess variation

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

The mean numbers of micronucleated polychromatic erythrocytes per 1000 were:

corn oil, 400, 600, 800 and 1000 mg/kg bw groups: 1.1 +/- 0.29, 1.2 +/-0.41, 1.2 +/-0.56, 0.5 +/-0.22 and 1.5 +/-0.41

positive control: 8.4 +/-0.24

All results are based on the mean of 5 animals, except 1000 mg/kg: 4 animals

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Under the conditions of this study the test substance did not induce micronucleus formation in vivo.

Executive summary:

An in vivo micronucleus test in male mice (5 per dose) was performed with intraperitoneal application (3 exposures on 3 consecutive days) with the test substance in corn oil at doses of 0, 400, 600, 800 and 1000 mg/kg bw/day. Cyclophosphamide served as positive control. 24 hours after the third injection, the mice were sacrificed and smears of femur bone marrow cells were prepared, fixed and stained. 2000 polychromatic erythrocytes were scored for frequency of micronucleated cells in each of 5 mice at each of 4 doses. No increase in micronucleated polychromatic erythrocytes could be observed in the treated groups. The positive control showed a mutagenic response, thus confirming the validity of this study.

Under the conditions of this study the test substance did not induce micronucleus formation in vivo.