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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
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:
mammalian bone marrow chromosome aberration test

Test material

Constituent 1
Chemical structure
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
Test material form:
liquid

Test animals

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


Administration / exposure

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
Doses / concentrationsopen allclose all
Dose / conc.:
300 mg/kg bw/day (nominal)
Remarks:
in water
Dose / conc.:
600 mg/kg bw/day (nominal)
Remarks:
in water
Dose / conc.:
1 200 mg/kg bw/day (nominal)
Remarks:
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.

Examinations

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.

Results and discussion

Test results
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.

Applicant's summary and conclusion

Conclusions:
Methyl ethyl ketoxime did not induce chromosomal aberrations in bone marrow cells of male or female rats.