Registration Dossier

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
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
less animals than required
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Test sample reference: NBW 8809/52
- Physical state: dark red powder
- Moisture: < 0.2%
- Assumed purity: lOO% w/w
- CTL reference: Y04203/002/00

Test animals

Species:
mouse
Strain:
other: C57BL/6JfCD-l
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Barriered Animal Breeding Unit, ICI Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK.
- Age at study initiation: 12-14 weeks for Phase I and 10-12 weeks for Phase II
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Housing: seven per cage on mobile mouse racks
- Diet (e.g. ad libitum): Parton Combined Diet [PCD]
- Water (e.g. ad libitum): filtered tap water ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 56-76%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and dark.

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
- Vehicle/solvent used: corn oil
- Concentration of test material in vehicle: volume of 10ml/kg bodyweight (0.1ml/10g) to groups 1, 2 and 3 but due to the viscous consistency of the suspension (at 500mg/ml) all further test substance suspensions/solutions were administered at a dose-volume of 20ml/kg bodyweight (0.2ml/10g).
Details on exposure:
Phase I : The test sample of the Substance was initially administered as a single intragastric dose to three groups of two female mice at dose levels of 20, 200, and 2000mg/kg. No mortalities were observed at any of the dose groups. Based on these data, five female and five male mice were dosed at a level of 5000mg/kg.

Phase II : animals were given a single dose of the test sample of Substance by the intragastric route, at dose levels of 5000mg/kg or 3l25mg/kg bodyweight.

Bone marrow smears were prepared at 24, 48 and 72 hours after dosing.
Duration of treatment / exposure:
single dose
Post exposure period:
24, 48, 72 hours
Positive control(s):
cyclophosphamide (CTL reference number Y01259/001)

Examinations

Tissues and cell types examined:
Bone marrow smears were stained with polychrome methylen blue and eosin to visualise the various cell types. 1000 polychromatic erythrocytes (PE) per slide were evaluated for the presence of micronuclei, and 1000 erythrocytes were counted to determine the percentage of PE in the total erythrocyte population to obtain an indication of cytotoxicity.

Results and discussion

Any other information on results incl. tables

No statistically or biologically significant increases in MPE above control levels were observed in either male or female mice treated with either dose level of the test sampl e of Substance H107597 at any of the sampling times investigated, indicating that the Substance is not clastogenlc in the mouse micronucleus test.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The results indicate that Substance is not clastogenic in the mouse micronucleus test.
Executive summary:

not clastogenic