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EC number: 231-554-3 | CAS number: 7631-99-4
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- Ecotoxicological Summary
- Aquatic toxicity
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- Short-term toxicity to fish
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Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Sodium nitrate is not mutagenic in Ames and chromosome aberration studies with human lymphocytes with and without metabolic activation. Several less reliable in vitro studies supported this conclusion. However, a chromosome aberration study in CHO cells did show positive effects without metabolic activation. Overall, sodium nitrate is considered negative in vitro.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 12-mar-2010 to 25-apr-2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- lymphocytes: human peripheral blood
- Details on mammalian cell type (if applicable):
- - Type and identity of media:
Blood samples
Blood samples were collected by venapuncture using the Venoject multiple sample blood collecting system with a suitable size sterile vessel containing sodium heparin. Immediately after blood collection lymphocyte cultures were started.
- Culture medium
Culture medium consisted of RPMI 1640 medium, supplemented with 20% (v/v) heat-inactivated (56°C; 30 min) foetal calf serum, L-glutamine (2 mM), penicillin/streptomycin (50 U/mL and 50 µg/mL respectively) and 30 U/mL heparin.
- Lymphocyte cultures
Whole blood (0.4 mL) treated with heparin was added to 5 mL or 4.8 mL culture medium (in the absence and presence of S9-mix, respectively). Per culture 0.1 ml (9 mg/mL) phytohaemagglutinin was added. - Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9-mix induced by a combination of phenobarbital and ß-naphthoflavone
- Test concentrations with justification for top dose:
- Dose range finding test:
Without and with S9-mix, 3hr exposure; 24 hr fixation: 10, 33, 100, 333 and 850 µg/mL
Without S9-mix, 24/48hr exposure; 24/48 hr fixation: 10, 33, 100, 333 and 850 µg/mL
First cytogenetic test:
Without and with S9-mix, 3 h exposure time, 24 h fixation time: 100, 333 and 850 µg/mL
Second cytogenetic test:
Without S9-mix, 24 hr exposure; 24 hr fixation: 100, 333 and 850 µg/mL
Without S9-mix, 48 hr exposure; 48 hr fixation: 100, 333 and 850 µg/mL
With S9-mix, 3 hr exposure; 48 hr fixation: 100, 333 and 850 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: exposure medium (RPMI 1640 medium )
- Justification for choice of solvent/vehicle: Test compound was soluble in exposure medium and exposure medium has been accepted and approved by authorities and international guidelines - Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without S9; in Hank's Balanced Salt Solution: 0.5 µg/ml for a 3 h exposure period, 0.2 µg/ml for a 24 h exposure period and 0.1 µg/ml for a 48 h exposure period
- Positive control substance:
- cyclophosphamide
- Remarks:
- with S9; in Hank's Balanced Salt Solution: 10 µg/ml
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: 48 hr
- Exposure duration: 3 hr (with and without S9-mix), 24 and 48 hr (without S9-mix)
- Fixation time (start of exposure up to fixation or harvest of cells): 24 and 48 hr
SPINDLE INHIBITOR (cytogenetic assays): colchicine
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: duplicates in two independent experiments
NUMBER OF CELLS EVALUATED: 100 metaphase chromosome spreads per culture
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index of each culture was determined by counting the number of metaphases per 1000 cells
OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes - Evaluation criteria:
- A test substance was considered positive (clastogenic) in the chromosome aberration test if:
a) It induced a dose-related statistically significant (Chi-square test, one-sided, p < 0.05) increase in the number of cells with chromosome aberrations.
b) A statistically significant and biologically relevant increase in the frequencies of the number of cells with chromosome aberrations was observed in the absence of a clear dose-response relationship.
A test substance was considered negative (not clastogenic) in the chromosome aberration test if none of the tested concentrations induced a statistically significant (Chi-square test, one-sided, p < 0.05) increase in the number of cells with chromosome aberrations. - Statistics:
- The incidence of aberrant cells (cells with one or more chromosome aberrations, gaps included or excluded) for each exposure group outside the laboratory historical control data range was compared to that of the solvent control using Chi-square statistics.
- Key result
- Species / strain:
- lymphocytes: human peripheral blood
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- - Effects of pH: No
- Effects of osmolality: No
- Precipitation: No precipitation was observed up to and including the top dose of 850 µg/mL (= 0.01 M)
RANGE-FINDING/SCREENING STUDIES:
- No toxicity was observed up to and including the top dose of 850 µg/mL
COMPARISON WITH HISTORICAL CONTROL DATA:
- The number of cells with chromosome aberrations found in the solvent and positive control cultures was within the laboratory historical control data range.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- No toxicity was observed up to and including the top dose of 850 µg/mL - Conclusions:
- The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical control data range. Positive control chemicals, mitomycin C and cyclophosphamide, both produced a statistically significant increase in the incidence of cells with chromosome aberrations, indicating that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly.
Natriumnitrat HQ unbehandelt (non-food grade) did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in the absence and presence of S9-mix, in either of the two independently repeated experiments.
Finally, it is concluded that this test is valid and that Natriumnitrat HQ unbehandelt (non-food grade) is not clastogenic in human lymphocytes under the experimental conditions described in the report. - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- The reliability and summary were made based on the HPV program adopted during OECD SIAM 25 (October 2007). Only limited information is available on methods and results; the article is a review article of more than 200 investigated substances. The strains used are no standard strains as recommended by the OECD, not all necessary substitutions are added. Details on positive controls were not given
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- - Deficiency/Proficiency: histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- other: S. typhimurium TA92 and TA94 were also used.
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9-mix (polychlorinated biphenyls induced, KC-400)
- Test concentrations with justification for top dose:
- 5 mg/plate (highest dose tested), 6 different concentrations (not given)
- Vehicle / solvent:
- phosphate buffer
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Positive control substance:
- not specified
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 minutes
- Exposure duration: 2 days
NUMBER OF REPLICATIONS:2 - Evaluation criteria:
- The result was considered positive if the number of revertant colonies found was twice or more that of the control. If no dose response was detected, additional experiments using different doses were performed.
- Statistics:
- not indicated
- Key result
- Species / strain:
- S. typhimurium, other: all strains tested
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Remarks:
- but tested up to limit concentrations
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- Sodium nitrate is not mutagenic in the Ames test.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- The reliability and summary were made based on the HPV program adopted during OECD SIAM 25 (October 2007). Only limited information is available on methods and results; the article is a review article of more than 200 investigated substances. The strains used are no standard strains as recommended by the OECD, not all necessary substitutions are added. Details on positive controls were not given. No GLP.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- no metabolic activation used,
cytotoxicity not measured,
exposure 24 and 48 h
100 metaphases investigated - GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- other: Chinese hamster fibroblast cell line, CHL
- Metabolic activation:
- without
- Test concentrations with justification for top dose:
- 5 mg/ml (highest dose tested),
maximum dose selected in a preliminary test (not reported)
3 different concentrations (not given) - Vehicle / solvent:
- physiological saline
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- not specified
- Positive control substance:
- not specified
- Details on test system and experimental conditions:
- - Exposure duration: 24 and 48 hr
- Colcemid was added 2 h prior to cell harvesting
- cells fized with acetic-acid methanol
- stained with Giemsa
- 100 metaphases observed - Evaluation criteria:
- The result was considered to be negative if the incidence of aberrations was less than 4.9%, equivocal if it was between 5.0 and 9.9% and positive if it was more than 10%.
- Statistics:
- For a quantitative evaluation of the clastogenic potential, the D20 was calculated, which is the dose (mg/ml) at which structural aberrations (including gaps) were detected in 20% of the metaphases observed.
In addition, the TR value was calculated, which indicates the frequency of cells with exchange-type aberrations per unit dose (mg/ml). - Key result
- Species / strain:
- other: Chinese hamster fibroblast cell line, CHL
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- 24% Struct. aberr at 48hr
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- other: incidence of aberrations usually less than 3.0%
- Untreated negative controls validity:
- other: incidence of aberrations usually less than 3.0%
- Positive controls validity:
- not specified
- Additional information on results:
- D20 5.73 mg/ml
TR 0.8
Also positive at 4.0 mg/ml at both 24 hr (10.0%) and 48 hour (10.0%). - Conclusions:
- may cause structural chromosomal aberrations, when incubated for 24 and 48 hours.
Referenceopen allclose all
No effects of Natriumnitrat HQ unbehandelt (non-food grade) on the number of polyploid cells and cells with endoreduplicated chromosomes were observed both in the absence and presence of S9-mix. Therefore it can be concluded that Natriumnitrat HQ unbehandelt (non-food grade) does not disturb mitotic processes and cell cycle progression and does not induce numerical chromosome aberrations
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
An in vivo chromosomal aberration and micronucleus test, UDS test, sperm abnormalitiy test, heritable translocation test all showed no genotoxicity.
Link to relevant study records
- 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
- 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
- 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 - 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. - 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
- 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
- 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.
- 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. - Endpoint:
- genetic toxicity in vivo, other
- Remarks:
- in vivo chromosomal aberration and micronucleus test
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- non-GLP
- Qualifier:
- no guideline followed
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- other: mouse (micronucleus evaluation) and rat (chromosomal aberration)
- Strain:
- other: Swiss mice, Wistar rats
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Biobreeding institute of Hygiene, Jassy.
- Age at study initiation: 10-14 weeks
- Diet: milk, bread, oats, carrot, sun flower seeds
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-19
- Humidity (%): 40-50 - Route of administration:
- oral: gavage
- Vehicle:
- 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) - Remarks:
- 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)
Basis: - 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. - Statistics:
- chi-sqaure analysis, compared to control group.
- Key result
- Sex:
- male
- Genotoxicity:
- positive
- Toxicity:
- yes
- Remarks:
- 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
- Endpoint:
- in vivo mammalian germ cell study: gene mutation
- Remarks:
- Sperm Abnormality
- 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).The study was not performed according to an OECD guideline. Only 1 exposure time (3 days) was used. However, negative and positive controls are reported and the results clearly indicate that treatment of mice with sodium nitrate did not result in sperm-head abnormality.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No guideline indicated
- GLP compliance:
- not specified
- Species:
- mouse
- Strain:
- C3H
- Sex:
- male
- Route of administration:
- oral: gavage
- Duration of treatment / exposure:
- 11 and 17 days after treatment mice were killed.
- Frequency of treatment:
- 3 times
- Post exposure period:
- Not indicated.
- Remarks:
- Doses / Concentrations:
600 and 1200 mg/kg/day
Basis: - No. of animals per sex per dose:
- 5 males/dose group
- Control animals:
- other: Vehicle control: water (same treatment as test substance treated groups). Positive control: MMS 75 mg/kg/day (i.p.) for 5 days.
- Tissues and cell types examined:
- caudal sperm
- Key result
- Sex:
- male
- Genotoxicity:
- not determined
- Remarks:
- Sperm abnormality was determined
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- No sperm abnormality was been observed.
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- 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
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No guideline indicated. The study was not performed according to the OECD guideline. Only 1 exposure time (3 days) was used, no clinical observations were made, and no reason was given for 1200 mg/kg/day as highest dose.
- GLP compliance:
- not specified
- Type of assay:
- unscheduled DNA synthesis
- 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
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 60
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- distilled water
- Details on exposure:
- dose levels sodium nitrate: 600 and 1200 mg/kg/day
dosed with sodium nitrate or vehicle control 3 times: 48, 24 and 1.5 h prior to thymidine injection
3H deoxy-thymidine injected into testis
positive control MMS injected immediately after thymidine injection - Duration of treatment / exposure:
- 17 days after treatment mice were killed.
- Frequency of treatment:
- 3 times, 48, 24 and 1.5 h prior to thymidine injection.
- Remarks:
- Doses / Concentrations:
600 and 1200 mg/kg/day
Basis: - No. of animals per sex per dose:
- 5 males/dose group.
- Control animals:
- yes, concurrent vehicle
- other: Positive control: methyl methanesulfonate, MMS 75 mg/kg (i.p.).
- Positive control(s):
- methyl methanesulfonate, MMS 75 mg/kg (i.p.).
- Tissues and cell types examined:
- Unscheduled DNA synthesis was determined in early to mid spermatids from epididymis.
Organs examined at necropsy: caudal sperm - Evaluation criteria:
- The UDS levels were presented as the incorporation of3H-deoxythymidine ([3H}dThd, in dpm) per 10 million sperms.
- Statistics:
- Student's t-test
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Conclusions:
- no unscheduled DNA synthesis was demonstrated
Referenceopen allclose all
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.
EFFECTS:
Dose (mg/kg/day) |
Number of abnormal sperm heads |
|
|
11 days after treatment |
17 days after treatment |
control |
16.0 ± 5.2 |
16.2 ± 3.2 |
600 |
14.8 ± 3.1 |
17.8 ± 5.5 |
1200 |
22.4 ± 8.7 |
25.8 ± 10.8 |
MMS (75) |
33.2 ± 6.1** |
47.0 ± 43.5 |
Sodium nitrate did not induce abnormalities in the sperm head of treated mice. No effects on rate of spermatogenesis.
STATISTICAL RESULTS:
No significant increases.
GENOTOXIC EFFECTS:
Dose (mg/kg/day) |
Incorporation of [3H]dThd (in dpm/106sperm) in male mouse germ cells determined 17 days after treatment |
control |
9.2 ± 2.1 |
600 |
8.8 ± 2.3 |
1200 |
9.0 ± 1.2 |
MMS (75) |
914.4 ± 168.7 |
No effects on rate of spermatogenesis.
STATISTICAL RESULTS:
No significant increases.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
In vitro studies
Sodium nitrate is not mutagenic in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, TA 92 and TA 94 with and without metabolic activation. No chromosomal aberrations or micronuclei were induced (not indicated whether metabolic activation was used). However, a chromosome aberration study in CHO cells did show positive effects without metabolic activation. Therefore, a new study was performed, and in this reliable OECD 473 guideline chromosome aberration study sodium nitrate did not show genotoxicity in human lymphocytes with or without metabolic activation. Several less reliable in vitro studies supported this conclusion.
In vivo studies
An in vivo chromosomal aberration and micronucleus test was negative. No unscheduled DNA synthesis was demonstrated in an UDS test. No sperm abnormalities or effect on rate of spermatogenesis were induced. Sodium nitrate was not mutagenic in a heritable translocation test. In a chromosome aberration/micronucleus study in rats and mice, no increase in chromosome aberrations were found when animals were treated twice. However, an increase in aberrant metaphases was observed in rats that were treated for 2 weeks with a 24 hour sampling. Such a repeated dosing and long sampling time is not according requirements, and as studies with acute dosing do not show positive findings with regard to chromosome aberrations this positive finding is considered not reliable. However, in the micronucleus study with the mice with a short sampling time (6 hours), two acute doses resulted already in an induction of micronuclei.
Based on all genotoxicity studies present, together with the findings that sodium nitrate does not induce tumor formation at high doses (see carcinogenicity section), it is concluded that sodium nitrate is not genotoxic.
Justification for selection of genetic toxicity endpoint
Several in vitro and in vivo studies on the substance are avaialble.
Justification for classification or non-classification
According to Annex I of Regulation (EC) No. 1272/2008 sodium nitrate is not classified based on the available data showing negative results from in vitro mammalian mutagenicity assays which do not support the outcome of one positive in vivo heritable germ cell mutagenicity test.
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