Sodium selenate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well-documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Chromosolmal effects of sodium selenite in vivo

Author:

Norppa H et al

Year:

1980

Bibliographic source:

Hereditas 93: 97-99 (1980)

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A single intraperitoneal injection with 0.8 mg Selenium/kg bw (= approx 20% of of the LD50 of selenium for mice) was administered and effects wre assessed after 24h. More details of the followed method are provided in the original publication..

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Sodium selenite

EC Number:

233-267-9

EC Name:

Sodium selenite

Cas Number:

10102-18-8

Molecular formula:

H2O3Se.2Na

IUPAC Name:

disodium selenite

Details on test material:

- Name of test material (as cited in study report): sodium selenite

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Medica
- Age at study initiation: 3 month

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

sterile water

Details on exposure:

Single intraperitoneal injection, 0.8 mg Selenium/kg bw. This dose is about one fifth of the LD50 of selenium for mice.

Duration of treatment / exposure:

24 hours

Frequency of treatment:

single intraperitoneal injection

Doses / concentrations

Remarks:

Doses / Concentrations:
0.8 mg Selenium/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

test substance: 12 males
control: 6 males

Control animals:

yes, concurrent vehicle

Positive control(s):

no

Examinations

Tissues and cell types examined:

Bone marrow cells
Spermatocytes

Details of tissue and slide preparation:

21 hours after exposure Colcemide (10µg/g bw) was injected i.p. into all animals. Three hours later the mice were killed by ether narcosis, and cytogenitec preparations were made of bone marrow and testis.

Bone marrow was rinsed out from both femurs by a medium consisting of three parts of Minimal Essential Medium (Orion), one part of pooled human Rh-positive AB serum and 0.05 µg/mL of Colcemid. Slides were prepared by the air drying method after 20 min. hypotonic treatment in pre-warmed (37°C), 0.075 mKCl and fixation in methanol-glacial acetic acid (3:1). They were stained in 5% Giemsa for 10 min. If possible, 100 diploid bone marrow metaphases were analyzed per animal from coded slides by one microscopist for the presence of chromosome and chromatid type aberrations and gaps.
Spermatocytes were prepared and stained according to the method described by Hoo and Bowles (1971). For each mouse, the frequency of cells with gonosomal and autosomal univalent, multivalents and fragments was determined, if possible, from 100 diakinesis-metaphase primary spermatocytes.
An interval of only 24 hours between the treatment and the evaluation of chromosomal changes in primary spermatocytes means that actually diakinesis has been treated. This stage is generally rather insensitive to to clastogens. But as some chemicals have been reported to affect even at this phase, the primary spermatocyte analysis is also included in the study.

Statistics:

Results were evaluated statistically by Fishers exact probability test (2-tailed).

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Negative controls validity:

valid

Additional information on results:

Both in the controls and selenite-treated mice, the frequencies of cells with chromosomal aberrations and gaps were low. Observed aberrations were chromatid type minutes or breaks. There was no difference in the occurrence of these lesions between the two groups.
No significant difference existed between the Sodium selenite treated and control mice for the frequencies of primary spermatocytes with univalents or fragments. No multivalents were found from either of the groups.
The dose of sodium selenite injected into the mice is high enough to induce toxic effect. Still, no rise was found in chromosomal aberration rates in bone marrow cells or primary spermatocytes of these animals.

Any other information on results incl. tables

Result from chromosomal abnormalities in bone marrow cells:

Treatment i.p.	No. of animals	No of cells evaluated:	Aberrations (gaps excluded)	Gaps only
Control	6	264	3 (1.1 %)	2 (0.8 %)
Sodium selenite (0.8 mg/kg bw)	12	666	3 (0.5 %)	9 (1.4 %)

Result from chromosomal abnormalities in primary spermatocytes:

Treatment i.p.	No. of animals	No of cells evaluated:	With fragments	With univalent
				Autosomal	Gonosomal
Control	6	225	1 (0.4 %)	0	2 (0.9 %)
Sodium selenite (0.8 mg/kg bw	12	982	2 (0.2 %)	1 (0.1 %)	1 (0.9 %)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Both in the controls and selenite-treated male mice, there was no difference between structural chromosomal aberrations or gaps in bone marrow cells and in the number of metaphase-diakinesis stages of primary spermatocytes with chromosomal fragments, autosomal univalents, or XY-univalents.

Executive summary:

Sodium selenite was injected intraperitoneally (0.8 mg Se/kg bw) into 12 male NMRI mice, while 6 control animals received sterile water. After 24 h, cytogenetic preparations of bone marrow and testis were made. Bone marrow of the Sodium selenite treated mice contained no more cells with structural chromosomal aberrations (0.5 % in 666 cells) or gaps (1.4 %) than that of the controls (1.1 % aberrations, 0.8 % gaps, in 264 cells). There was also no difference between the two groups in the number of metaphase-diakinesis stages of primary spermatocytes with chromosomal fragments (0.2 % in 982 cells in sodium selenite – group, 0.4 % in 225 cells in controls), autosomal univalent (0.1 % in sodium selenite – group, 0.0 % in controls), or XY-univalents (0.1 % in sodium selenite – group, 0.9 % in controls).