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Toxicological information

Genetic toxicity: in vivo

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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:
1997
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: 8 weeks and 2 days
- Weight at study initiation: 29.8-37.8 g (male) and 23.3-28.8 g (female)
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: five per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 15
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: Peanut oil
- Justification for choice of solvent/vehicle:
- Concentration of test material in vehicle:
- Amount of vehicle (if gavage or dermal): 10 mL
- Type and concentration of dispersant aid (if powder):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
24, 48, and 72 hours
Frequency of treatment:
Once
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
6 mg/kg
Basis:

Remarks:
Doses / Concentrations:
12 mg/kg
Basis:

Remarks:
Doses / Concentrations:
24 mg/kg
Basis:

No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Route of administration: sterile water
- Doses / concentrations: 60 mg/kg

Examinations

Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
Range finding study performed to find the maximum tolerated dose

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):


DETAILS OF SLIDE PREPARATION:
Slides fixed with methanol and stained in May-Grunwald solution followed by Giemsa.

METHOD OF ANALYSIS:
Scored for micronuclei and the polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE) cell ration.

OTHER:
Evaluation criteria:
Statistically sifnificant dose-related increase in micronucleated PCE's and the detection of a statictically sifnificant postive response for at least one dose level.
Statistics:
The frequency of micronucleated polychromatic erythrocytes between treated groups and vehicle controls were compared. Tests included Cochran-Armitage test for trend, a one-way analysis of variance and Dunnett’s procedure.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative