Registration Dossier
Registration Dossier
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EC number: 605-399-0 | CAS number: 165252-70-0
Genetic toxicity: in vivo
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
- Study period:
- 18/11/1994 - 15/03/1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP, Guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: JMAFF 59 NohSan no. 4200 (1985)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- (RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine
- EC Number:
- 605-399-0
- Cas Number:
- 165252-70-0
- Molecular formula:
- C7H14N4O3
- IUPAC Name:
- (RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine
- Test material form:
- solid: crystalline
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: BDF1 (C57BL/6 x DBA/2)
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Sex: Male
Age/weight at study initiation: Weighing 24.8 – 27.1g
Number of animals per group: 6 males per group
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- 0.5% aqueous carboxymethyl cellulose solution
- Details on exposure:
- 2 applications
- Duration of treatment / exposure:
- 2 days
- Frequency of treatment:
- Daily dosing for 2 days (24 hour interval between applications)
- Post exposure period:
- 24 hours after final treatment
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0 (vehicle), 270, 540 and 1080 mg/kg/day on 2 consecutive days, 24 hours apart (total doses: 540, 1080 or 2160 mg/kg).
Basis:
nominal conc.
- No. of animals per sex per dose:
- 6 males per group
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Single intraperitoneal injection of 2 mg/kg Mitomycin C(MMC), 24 hours before necropsy, as a positive control group.
Examinations
- Tissues and cell types examined:
- Bone marrow
- Details of tissue and slide preparation:
- Clinical signs: Yes, after treatment and before sacrifice.
Body weight: Yes, first day of treatment and on the day of sacrifice.
Tissue: Bone marrow:
Number of animals: all animals
Number of cells: 2000
Time points: 24 h after final treatment
Type of cells: Micronucleated polychromatic erythrocytes in bone marrow - Evaluation criteria:
- Parameters: Polychromatic/normochromatic erythrocytes ratio
- Statistics:
- The incidence of MNPCE was subjected to the shochastic method by Kastenbaum and Bowman, and the ratio of PCE was subjected to the Dunnett's t-test for the analysis of significant differences.
Results and discussion
Test results
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- There were no deaths during the treatment period and no signs of toxicity including body weight change were evident at any dose level. The MNPCE frequencies and PCE/total erythrocyte ratios of all dinotefuran-treated groups were comparable to and not significantly different from control values.
In contrast, mitomycin C produced a statistically significant increase in the MNPCE frequency and a statistically significant decrease in the PCE/total erythrocyte ratio.
Since the incidences of MNPCE and the ratios of PCE/total erythrocytes in both the vehicle control and positive control groups were within the laboratory historical control ranges, the test was considered to be valid.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Dinotefuran at dose levels approaching the maximum tolerated dose does not induce the formation of micronuclei and does not inhibit spindle formation in the bone marrow of mice.
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