Acetophenone

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February to June 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Acetophenone

EC Number:

202-708-7

EC Name:

Acetophenone

Cas Number:

98-86-2

Molecular formula:

C8H8O

IUPAC Name:

1-phenylethanone

Details on test material:

- Name of test material (as cited in study report): acetophenone
- Physical state: liquid
- Analytical purity: 99.36%
- Lot/batch No.: E 38/06
- Expiration date of the lot/batch:
- Storage condition of test material: room temperature

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Arald Winkelmann
- Age at study initiation: minimum 7 weeks (6-12 weeks at start of acclimation)
- Weight at study initiation:
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: groups of 5
- Diet (e.g. ad libitum)
- Water (e.g. ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 55 +- 10
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: cotton seed oil
- Justification for choice of solvent/vehicle: solubility and relative non-toxicity
- Concentration of test material in vehicle: 10.3-51.5 mg/mL
- Amount of vehicle : 10 mL/kg bw

Frequency of treatment:

single

Post exposure period:

44 hrs; additionally 68 hrs fur a further negative control and high-dose group

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

515 mg/kg bw (total dose)

Doses / concentrations 2

Dose / conc.:

257.5 mg/kg bw (total dose)

Doses / concentrations 3

Dose / conc.:

103 mg/kg bw (total dose)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide
- Route of administration: i.p.
- Doses / concentrations: 40 mg/kg bw

Examinations

Tissues and cell types examined:

peripheral blood erythrocytes

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
Dose selection based on preceeding study on toxicity for determination of MTD: MTD = 515 mg/kg bw/d after intraperitoneal application; doses correspond to 0.2-, 0.5- and 1-fold MTD

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
44 and 68 hrs after application

METHOD OF ANALYSIS:
at least 10,000 cells scored per animal

Evaluation criteria:

Relative PCE = proportion of immature polychromatic erythrocytes among total number of erythrocytes
Criteria for positive results:
- dose-related increase of micronucleated erythrocytes
- biologically relevant increase of micronucleated erythrocytes for at least one of the dose groups
- according to OECD Guideline 422 a statistitically significant increase additionally to the biologically relevant increase

Statistics:

Non-parametric Mann-Whitney test

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Clinical signs of toxicity in test animals: at the MTD all treated animals showed reduction of spontaneous activity, prone position, apathy, palpebral closure, uncoordinated movements
- Evidence of cytotoxicity in tissue analyzed: yes, relative changes of PCE

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no increase for test substance
- Appropriateness of dose levels and route: yes, testing up to MTD
- Statistical evaluation: no significant changes

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative
There were no increased incidences of micronuclei in mouse peripheral blood erythrocytes.

Executive summary:

No increased incidences of micronuclei were observed in mouse peripheral blood erythrocytes after single intraperitoneal application of dosages of 103, 257.5, 515 mg/kg bw corresponding to 0.2, 0.5 and 1.0 of the MTD. The test was performed according to OECD Guideline 474 with sampling times of 44 and 68 hrs.