Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key 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, mitotic index not reported and gaps not reported.

Data source

Reference
Reference Type:
publication
Title:
Genotoxicity studies of sodium selenite and its effect on methyl-methanesulfonate-induced chromosome damage
Author:
Slapsyte, G.; Sukackaite, A.
Year:
2003
Bibliographic source:
Biologija, Nr. 1; ISSN 1392-0146, 41-44

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The genotoxic activity of sodium selenite was studied using chromosome aberration (CA) test in human peripheral blood lymphocytes in vitro.
GLP compliance:
no
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sodium selenite
- Molecular formula (if other than submission substance): Na2SeO3
- Physical state: solid
No further details are given.

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
lymphocytes: from human donors
Details on mammalian cell type (if applicable):
Whole peripheral blood obtained from healthy donors was used.
- Type and identity of media: The blood was grown in RPMI 1640 medium containing 12% newborn calf serum, 2mM alpha-glutamine, 7.8 µg/mL phytohaemagglutinin P, 50 µg/mL gentamycin and 10 µg/mL 5-bromo-2'-deoxyuridine.
The cultures were incubated at 37°C for 72 hours treated with 0.5 µg/mL colchicine for at least 3 hours of incubation, exposed to 0.075M KCl for 20 minutes and fixed in 3:1 methanol:acetic acid.
Additional strain / cell type characteristics:
not specified
Metabolic activation:
not specified
Test concentrations with justification for top dose:
0.05, 0.1, 0.25, 0.5, 0.75 µg/mL (limited by cytotoxicity)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: The test item was dissolved and diluted in RPMI 1640 medium.
- Justification for choice of solvent/vehicle: no data

Working solution of the test item was made just before treatment. 50 µL solution was applied to each culture flask.
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
Migrated to IUCLID6: 0.02 µg/mL
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 24 hours

STAIN (for cytogenetic assays): Flame-dried chromosome preparations were made and differentially stained by fluorescence plus Giemsa technique.

NUMBER OF REPLICATIONS: Duplicate whole blood cultures were used for each treatment group.

NUMBER OF CELLS EVALUATED: 200 first-mitotic division cells for chromosome aberrations were analysed.

DETERMINATION OF CYTOTOXICITY
no data

OTHER: replicative index (RI)
The frequency of first, second and third mitotic division cells were scored from no less than 200 cells for each test condition to determine the RI.
Evaluation criteria:
no data
Statistics:
All statistical analyses were performed using InStat V2.02 (GraphPad Software, San Diego, CA, USA) statistical package.

Results and discussion

Test results
Species / strain:
lymphocytes: from human
Metabolic activation:
not specified
Genotoxicity:
negative
Remarks:
Sodium selenite did not increase the frequency of CAs at concentrations up to the top concentration of 0.75 µg/mL. At this concentration sodium selenite induced a borderline, but statistically significant increase of aberrations.
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
No further details are given.

RANGE-FINDING/SCREENING STUDIES: no data

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY: Concentrations of sodium selenite >1 µg/mL were determined to be cytotoxic.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Sodium selentite significantly decreased the RI values. However, no dose-related effect was observed (r² = 0.03947; P = 0.7059).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The study reports no biological relevant increase in chromosome aberrations following 24h exposure. The maximum dose was limited by cytotoxicity. Clastogenic effects were reported at top concentrations for which a significant cytotoxicity was observed.