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Toxicological information

Genetic toxicity: in vivo

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Administrative data

genetic toxicity in vivo
Type of genotoxicity: other: in vivo chromosomal aberration and micronucleus test
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non GLP. The read-across rationale can be found in the category approach document attached in Section 13.

Data source

Reference Type:
Chromosomal aberrations and micronuclei in rat and mouse bone marrow cells by sodium nitrate.
Luca, D., Raileanu, L., Luca, V., and Duda, R
Bibliographic source:
Mutation Research. 155:121-125.

Materials and methods

Test guideline
no guideline followed
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium nitrate
EC Number:
EC Name:
Sodium nitrate
Cas Number:
Molecular formula:
sodium nitrate

Test animals

other: mouse (micronucleus evaluation) and rat (chromosomal aberration)
other: Swiss mice, Wistar rats
Details on test animals or test system and environmental conditions:
- Source: Biobreeding institute of Hygiene, Jassy.
- Age at study initiation: 10-14 weeks
- Diet: milk, bread, oats, carrot, sun flower seeds

- Temperature (°C): 18-19
- Humidity (%): 40-50

Administration / exposure

Route of administration:
oral: gavage
distilled water
Duration of treatment / exposure:
Twice in 24 hours (8 mice/group for micronuclei evaluation, animals killed 6 hr after last dose)
Twice in 24 hours (4 rats/group for chromosomal aberration analysis, animals killed 24 hr after last dose)
Daily for 2 weeks (6 rats/group for subacute test for chromosomal aberration analysis, animals killed 24 hr after last dose)
Doses / concentrations
Doses / Concentrations:
108, 323, 969 and 2,906 mg/kg bw (sodium nitrate) 78.5, 235.5, 706.6 and 2120 mg/kg bw (nitrate)

No. of animals per sex per dose:
8 mice/group for micronuclei evaluation, animals killed 24 hr after last dose
4 rats/group for chromosomal aberration analysis, animals killed 24 hr after last dose
6 rats/group for subacute test for chromosomal aberration analysis, animals killed 24 hr after last dose
Control animals:
yes, concurrent vehicle
Positive control(s):
no data


Tissues and cell types examined:
micronuclei evaluation (mice) and chromosomal aberration analysis (rats)
Details of tissue and slide preparation:
The bone marrow preparations for chromosomal aberrations analysis were made according to Killian et al 1977. 50 metaphase cells per animal.
The preparations for MN analysis by the method of Schmid 1975. PCEs and NCEs were counted, at least 1000 polychromatic cells per mouse.
Slides were scored blindly.
chi-sqaure analysis, compared to control group.

Results and discussion

Test results
indication for a cytotoxic effect of the nitrate in the marrow.
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
not specified

Any other information on results incl. tables

After acute exposure to nitrate, no significant difference between the frequency of chromosomal aberrations in the exposed and control groups was detected in either rats or mice with the exception of mice receiving a dose of 706.6 mg NO3/kg. Rats treated for two weeks and long sampling time (24 hr) had significant increases in aberrant metaphases. Due to these shortcomings, 2 weeks of treatment and too long sampling, the positive efects may have been induced by this and can be disregarded. After acute exposure of mice, the frequency of micronucleated polychromatic erythrocytes increased significantly only at the lower doses of nitrate. This occurrence was probably masked at the higher doses by the invasion of the marrow by peripheral blood, which probably indicates a cytotoxic effect of the nitrate in the marrow. The sampling time was only 6 hr, too short, even though positive results were observed.

Positive controls were not included as required under OECD test guidelines; repeated dosing for 2 weeks is inconsistent with OECD TG 475.

Applicant's summary and conclusion