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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo, other
Remarks:
heritable translocation test
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The reliability and summary were made based on the HPV program adopted during OECD SIAM 25 (October 2007). non GLP

Data source

Reference
Reference Type:
publication
Title:
In vivo genotoxicity of nitrate and nitrites in germ cells for male mice. I. Evidence for gonadal exposure and lack of heritable effects.
Author:
Alavantic, D., Sunjevaric, I., Pecevski, J., Bozin, D., and Cerovic, G.
Year:
1988
Bibliographic source:
Mutation Research.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
OECD 485 is not followed, not GLP, no positive control, less animals used
GLP compliance:
not specified
Type of assay:
heritable translocation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium nitrate
EC Number:
231-554-3
EC Name:
Sodium nitrate
Cas Number:
7631-99-4
Molecular formula:
HNO3.Na
IUPAC Name:
sodium nitrate
Test material form:
solid: crystalline
Details on test material:
- Physical appearance: not indicated
- Purity: not indicated
- Batch No.: not indicated
- Supplier: not indicated

Test animals

Species:
mouse
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10-12 weeks
- Housing: in wire-topped polycarbonate cages
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
distilled water
Duration of treatment / exposure:
14 days
Frequency of treatment:
daily
Post exposure period:
At 10 days after the last treatment, each male was mated with 2 virgin females. Mating interval was 7 days.
At 5 weeks after treatment, treated and control males were killed by cervical dislocation for cytogenetic analysis.
Doses / concentrations
Remarks:
Doses / Concentrations:
600 and 1,200 mg NaNO3/kg/day
Basis:

No. of animals per sex per dose:
25 males
Control animals:
yes, concurrent vehicle
Positive control(s):
no data

Examinations

Tissues and cell types examined:
P1 generation:
- cytogenetic analysis performed
- spermatocytes collected from all males, analysed in diakinesis-metaphase I.
- 100 cells per male analysed

F1 generation:
- F1 males were killed at 10-12 weeks.
- cytogenetic analysis performed on up to 3 males per litter from treated P males, and in 25 F1 males from controls.
- spermatocytes collected, analysed in diakinesis-metaphase I.
- 50 cells per F1 male analysed

Details of tissue and slide preparation:
chromosomal preparations made by Evans' air drying method, stained by orcein.
Statistics:
Student's t-test

Results and discussion

Test resultsopen allclose all
Key result
Sex:
male
Genotoxicity:
negative
Remarks:
no translocations in P1 males
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
not specified
Key result
Sex:
male
Genotoxicity:
negative
Remarks:
no heritable chromosomal translocations in F1 males
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
Sex chromosomal univalency was significantly higher at both doses.

Applicant's summary and conclusion

Conclusions:
The substance was not mutagenic: negative no translocations in P1 males, no heritable chromosomal translocations in F1 males

Sex chromosomal univalency was significantly higher at both doses.