Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

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: Reliable with restrictions, as purity/identity of test item missing and experimental procedure poorly described. Due to reporting deficiencies this reference will only be used as supportive information.

Data source

Reference
Reference Type:
publication
Title:
Micronucleus induction by chromium and selenium, and suppression by metallothionein inducer.
Author:
Itoh S, Shimada H.
Year:
1996
Bibliographic source:
Mutat. Res. 367, 233-236

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The clastogenic effect of selenium compounds in mouse bone marrow cells has been investigated.
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Selenious acid
- Molecular formula (if other than submission substance): H2SeO3
- Physical state: solid
No further details are given.

Test animals

Species:
mouse
Strain:
other: Slc:ddY
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC Inc. (Hamamatsu, Shizuoka)
- Age at study initiation: 8-week old
- Housing: 5 mice per metal cage
- Diet: ad libitum
- Water: ad libitum

No further details are given.

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used:physiological saline
No further details.
Details on exposure:
No further details are given.
Duration of treatment / exposure:
for 2 consecutive days
Frequency of treatment:
once a day
Post exposure period:
24 hours
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.625 mg/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1.25 mg/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
2.5 mg/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
5 mice per treatment group
Control animals:
yes, concurrent vehicle
Positive control(s):
mitomycin C
- Doses / concentrations: 0.5 mg/kg

Examinations

Tissues and cell types examined:
bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: The dose levels were determined on the basis of preliminary dose finding tests for maximum survival dose.

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Animals were killed by cervical dislocation at 24 hours after the second administration and the bone marrow was flushed into a tube containing foetal bovine serum.

DETAILS OF SLIDE PREPARATION: Bone marrow smears were prepared and stained with acridine orange.

METHOD OF ANALYSIS: For each animal, 1000 polychromatic erythrocytes (PCE) were scored for micronuclei (MN) and the frequency of micronucleated polychromatic erythrocytes (MNPCE) was expressed as percent of PCE. A number of PCE in 1000 total erythrocytes (PCE plus normochromatic erythrocytes) were also recorded.
Evaluation criteria:
no data
Statistics:
The Kastenbaum and Bowman method (1970) was used for statistical analysis of MNPCE.

Results and discussion

Test results
Sex:
male
Genotoxicity:
positive
Remarks:
H2SeO3 induced a significant increase in MN-PCE at the highest dose.
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
No further details are given.

Any other information on results incl. tables

Induction of MNPCE by H2SeO3

 Compound Dose (mg/kg)  MNPCE (%)  range  PCE (%)  range
Control**   0.14 +/- 0.05  0 -0.3  58.3 +/- 2.9  49.1 -77.9
 H2SeO3  0.625  0.14 +/- 0.07 0 -0.3   61.8 +/- 2.3  57 -70.4
   1.25  0.20 +/- 0.05  0.1 -0.4  53.7 +/- 2.7  45.6 -58.7
   2.5  0.30 +/- 0.08  0.2 -0.6  61.0 +/- 3.0  51.8 -67.6
   5.0  2.50 +/- 0.61*  1.0 -4.1 45.2 +/- 3.3   35.8 -55.0
 mitomycin C  0.5  2.27 +/- 0.15*  1.0 -3.8  58.7 +/- 1.1  46.5 -65.9

 * Significant difference from current control (p<0.01)

** Sum of 4 experiments

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Increase in micronucleated cells only at very high, nearly lethal dose, questionable biological relevance.
A significant increase in micronucleated cells was observed, with a clear positive finding in the maximum dose of 5 mg/kg. All lower dose levels were in the range of the control (0.0-0.3% MNPCE). However, the dose selection was not clearly justified and a description of the toxic effects is lacking. As stated below one might speculate that the maximum dose already showed signs of near-lethal toxicity, making this positive finding of questionable biological significance.