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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reasonably well described study with minor reporting deficiencies, i.e. purity of the test substance not stated.

Data source

Reference
Reference Type:
publication
Title:
Orthovanadate increased the frequency of aneuploid mouse sperm without micronucleus induction in mouse bone marrow erythrocytes at the same dose level
Author:
Attia, S. M.; et al.
Year:
2005
Bibliographic source:
Mut. Res. 583, 158-167

Materials and methods

Test guideline
Guideline:
other: no information available if test was conducted according to guideline
Principles of method if other than guideline:
The objective of the current study was to investigate the ability of orthovanadate to induce micronuclei in mouse bone marrow cells.
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): orthovanadate
- Physical state: solid

Test animals

Species:
mouse
Strain:
other: (102/E1 x C3H/E1)F1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animals bred in the mouse colony of the GSF-Research Center.
- Age at study initiation: 10-14 weeks
- Weight at study initiation: 25-29g
- Assigned to test groups randomly: yes
- Diet: ad libitum; mouse standard pellet food
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hours dark/light cycle
No further details are given.

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: 0.9% saline
No further details are reported.
Details on exposure:
No further details are given.
Duration of treatment / exposure:
once
Frequency of treatment:
single administration
Post exposure period:
24 hours
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg body weight
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1 mg (VO4 3-)/kg body weight
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5 mg (VO4 3-)/kg body weight
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
15 mg (VO4 3-)/kg body weight
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
25 mg (VO4 3-)/kg body weight
Basis:
nominal conc.
No. of animals per sex per dose:
Each treatment group and vehicle control group consisted of 5 randomly assigned animals.
Control animals:
yes, concurrent vehicle
Positive control(s):
No positive control substance was tested.

Examinations

Tissues and cell types examined:
bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: no data

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): No further details are given.

DETAILS OF SLIDE PREPARATION: Bone marrow smears were prepared and stained with May-Grünwald-Giemsa. At least 4 slides were made for each animal and allowed to dry overnight. Two slides per animal were stained with May-Grünwald-Giemsa solutions according to the standard technique for conventional assessment of the MN frequencies. The remaining unstained slides were stored at -20°C for later use to distinguish between the induced clastogenic and aneugenic effects by identifying the origin of MN with FISH using the minor satellite DNA probe.

METHOD OF ANALYSIS: All slides were coded for microscopic analysis at 1000x magnification. Per animal, 1000 polychromatic erythrocytes (PCE) from each of two slides were scored for the presence of MN. The frequencies of PCE were determined in slide areas where 2000 normochromatic erythrocytes (NCE) could be counted to determine a shift in erythroblst proliferation. The values were expressed as % PCE of the total erythrocyte counts to determine a reduction of erythroblast proliferation. MNNCE were also recorded.

OTHER: No further details are given.
Evaluation criteria:
No details are reported.
Statistics:
The Mann-Whitney U-test or qui-square test with Yate's correction were used to determine statistical differences (p<0.05) between treated groups and the solvent control group.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Remarks:
Treatment at the doses tested caused no significant increases in the frequencies of MNPCE.
Toxicity:
no effects
Remarks:
The ratio of PCE to total erythrocytes did not indicate cytotoxic effects in any of the treated groups.
Vehicle controls valid:
yes
Negative controls valid:
not examined
Positive controls valid:
not examined
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
No details available.

RESULTS OF DEFINITIVE STUDY
Orthovanadate treatment at the doses tested caused no significant increases in the frequencies of MNPCE compared to the solvent control. This, the data did not indicate an induction of MN in bone marrow erythrocytes of the male hybrid mice used at the given treatment regimen.
- Induction of micronuclei (for Micronucleus assay): Since no induction of MNPCE in bone marrow erythrocytes was found with the test substance, the distinction between the clastogenic and aneugenic effects by identifying the origin of MN with centromeric DNA probes was omitted.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Under these test conditions, sodium orthovanadate, is not mutagenic in bone marrow cells after treatment with a single intraperitoneal injection up to a concentration of 25 mg (VO4 3-)/kg body weight.
Executive summary:

The objective of the current study was to investigate the ability of sodium orthovanadate to induce micronuclei in mouse bone marrow cells.

Sodium orthovanadate was investigated by the micronucleus test at i.p. doses of 1, 5, 15 or 25 mg ( VO43 -) / kg body weight, followed by bone marrow sampling 24 hours after treatment. None of the orthovanadate doses caused a significant increase in the rates of micronuclei (MN).