2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo

Remarks:

Type of genotoxicity: genome mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

EC Number:

400-600-6

EC Name:

2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Cas Number:

71868-10-5

Molecular formula:

C15 H21 N O2 S

IUPAC Name:

2-methyl-1-[4-(methylsulfanyl)phenyl]-2-(morpholin-4-yl)propan-1-one

Test animals

Species:

hamster, Chinese

Strain:

other: Chinese hamster (Cricetulus griseus) random outbred strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Tierfarm, Sisseln, Switzerland
- Age at study initiation: females: 6-10 weeks, males: 4-9 weeks
- Weight at study initiation: females: 20-30 g; males: 21-31 g
- Housing: individually
- Diet (e.g. ad libitum): NAFAG No.924, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 51-54
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

0.5 % aqueous solution of sodium carboxymethylcellulose (CMC) plus 0.1 % Tween 80 (Tw 80)

Duration of treatment / exposure:

daily on 2 consecutive days

Frequency of treatment:

once a day

Post exposure period:

24 hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

750 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

1 500 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

3 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide (128 mg/kg)

Examinations

Tissues and cell types examined:

bone marrow cells

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION: Bone marrow was harvested from the shafts of both femurs. In a siliconized pipette filled with approx. 0.5 µl rat serum the bone marrow was drawn up. In order to receive a homogeneous suspension the content of pipette was aspirated gently about three times. Small drops of the mixture were transferred on the end of a slide, spread out by pulling it behind a polished cover glass and the preparations were air-dried. Three hours later, the slides were stained in undiluted May-Gruenwald solution for 2 min then in May-Gruenwald solution/water 1/1 for
2 min and then in Giemsa's, 40 % for 20 min. After being rinsed in methanol 55 % for 5-8 sec and washed off twice in water, they were left immersed in water for approx. 2 min. After rinsing with distilled water and air-drying, the slides were cleared in Xylol and mounted in Eukitt.

METHOD OF ANALYSIS: The slides of three female and three male animals were examined. 1000 bone marrow cells each were scored per animal and the following anomalies were registered: a) Single Jolly bodies, b) fragments of nuclei in erythrocytes, c) micronuclei in erythroblasts, d) micronuclei in leucopoietic cells, e) polyploid cells.

Statistics:

The significance of difference was assessed by x²-test

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not examined

Additional information on results:

RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels: a) Single Jolly bodies, b) fragments of nuclei in erythrocytes, c) micronuclei in erythroblasts, d) micronuclei in leucopoietic cells, e) polyploid cells
- Induction of micronuclei (for Micronucleus assay): In all dosage groups the percentage of cells displaying anomalies of nuclei did not differ significantly from the negative control.
- Statistical evaluation: The significance of difference was assessed by χ2-test

Applicant's summary and conclusion

Conclusions:

The test substance failed to induce statistically significant genome mutations under the conditions of the test.