Registration Dossier

Administrative data

Endpoint:
in vivo mammalian germ cell study: gene mutation
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
None

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Japanese Industrial Safety and Health Law guideline
Principles of method if other than guideline:
None
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:
None
Specific details on test material used for the study:
None

Test animals

Species:
mouse
Strain:
not specified
Details on species / strain selection:
None
Sex:
male
Details on test animals and environmental conditions:
Specific Pathogen Free(SPF) male mice of BDF1(C57BL/6xDBA/2) strain Pilot study Main Study a) Receipt of animals Feb. 15, 1990 March 15, 1990 (age) (8 weeks old) (8 weeks old)b) Number ordered Male: 50 Male: 45c) Date of administration Feb. 26, 1990 March 26, 1990 (age) (9 weeks old) (9 weeks old)d) Body weight at 25.7-27.9g 24.3-28.7g administration period

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Corn oil
Details on exposure:
None
Duration of treatment / exposure:
None
Frequency of treatment:
None
Post exposure period:
None
No. of animals per sex per dose:
Female: 1250 mg/kg; No. of animals: ; Sacrifice times: hoursFemale: 2500 mg/kg; No. of animals: ; Sacrifice times: hoursFemale: 5000 mg/kg; No. of animals: ; Sacrifice times: hours
Positive control(s):
Mitomycin C with saline

Examinations

Tissues and cell types examined:
None
Details of tissue and slide preparation:
None
Evaluation criteria:
None
Statistics:
None

Results and discussion

Test results
Key result
Sex:
female
Toxicity:
yes
Remarks:
Doses producing toxicity:>= 2500 mg/kg
Additional information on results:
Observations:The test substance induced significant cytotoxicity in mouse bone marrow cells at 5000 mg/kg (p<0.005). However, the incidence of MNPCE at any of the dose levels was comparable to that in the control group and there was no statistically significant increase.Mitomycin C-treated (2mg/kg) mice, the positive control, caused a statistically significant increase in the frequency of MNPCE. clinical symptoms: no lethal effects.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Negative is the in vivo chromosome aberration test.
Executive summary:

The in-vivo mouse micronucleus test was conducted using BDF (C57BL/6xDBA/2) hybrid to assess the potential of D-523 to induce micronucleated erythrocyte. Dose levels of 1250, 2500 and 5000 mg/kg were selected on the basis of a erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) were counted 24 hours after a single intraperitoneal injection of FAT 40554.

The test substance, FAT 40554, induced significant cytotoxicity in mouse bone marrow cells at 5000 mg/kg (p<0.05). However, the incidence of MNPCE at any of the dose levels and comparable to that in the solvent control group and there was no statisticakky significant increase.