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Carcinogenicity

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Description of key information

Several carcinogenicity studies are present with sodium nitrate, which are evaluated by WHO and IARC. The data do not indicate carcinogenic potential of sodium nitrate.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
carcinogenicity: oral
Type of information:
other: Evaluation by competent authority
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This publication represents a peer-reviewed evaluation of all published data on carcinogenic potential of nitrates.
Details on results:
The monograph includes evaluation of all published data on sodium nitrate up to 2006.
Conclusions:
There is inadequate evidence in humans for the carcinogenicity of nitrate in food.
There is inadequate evidence in humans for the carcinogenicity of nitrate in drinking water.
There is inadequate evidence in experimental animals for the carcinogenicity of nitrate.
However, ingested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic to humans (Group 2A).
There is an active endogenous nitrogen cycle in humans that involves nitrate and nitrite, which are interconvertible in vivo. Nitrosating agents that arise from nitrite under acidic gastric conditions react readily with nitrosatable compounds, especially secondary amines and amides, to generate N-nitroso compounds. These nitrosating conditions are enhanced following ingestion of additional nitrate, nitrite or nitrosatable compounds.
Some of the N-nitroso compounds that could be formed in humans under these conditions are known carcinogens.
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The reliability and summary were made based on the HPV program adopted during OECD SIAM 25 (October 2007).
Qualifier:
no guideline followed
GLP compliance:
not specified
Specific details on test material used for the study:
special grade reagent; purity 99.5%
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
104-weeks
Frequency of treatment:
ad libitum
Post exposure period:
21 weeks
Remarks:
Doses / Concentrations:
2.5%, 5.0% in the diet
Basis:

No. of animals per sex per dose:
The animals were divided into groups comprising 50 male and 50 female rats.
Control animals:
yes, concurrent no treatment
Dose descriptor:
NOAEL
Effect level:
>= 5 other: %
Sex:
male/female
Basis for effect level:
other: no increase in the incidence of malignant tumours

No. with tumors (0% ; male) = 47 (94%)

No. with tumors (0%; female) = 46 (92%)

No. with tumors (2.5%; male) = 50 (100%)

No. with tumors (2.5%; female) = 43 (86%)

No. with tumors (5%; male) = 48 (96%)

No. with tumors (5%; female) = 39 (80%)

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The reliability and summary were made based on the HPV program adopted during OECD SIAM 25 (October 2007). The information given is limited to the below mentioned.
Qualifier:
no guideline followed
GLP compliance:
no
Species:
rat
Strain:
not specified
Sex:
male
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
273 days
Frequency of treatment:
ad libitum
Post exposure period:
None.
Dose / conc.:
4 other: g/L
No. of animals per sex per dose:
18-34 males/group
Control animals:
yes, concurrent no treatment
Details on study design:
Study was conducted as a limit test.
Dose descriptor:
NOAEL
Effect level:
>= 4 000 mg/L drinking water
Basis for effect level:
other: no hyperplastic changes in the urothelium or carcinomas were found when treated with sodium nitrate alone.

No marked clinical signs were noted that could be related to a toxic effect. After 9 months, macrohaematuria had developed in 2 rats receiving BBNA and sodium nitrate as a consequence of tumour break up. Treatment with BBNA and sodium nitrate, tripled the percentage of carcinoma’s and altered the nature of pre-tumourous changes in the direction of greater malignancy. In the group with sodium nitrate alone no hyperplastic changes in the urothelium or carcinomas were found.

Conclusions:
Subsequent exposure via the drinking water to the carcinogen BBNA and sodium nitrate enhanced the urinary bladder carcinogenisis in rats most likely because of the promotional effect of sodium nitrate (or possibly of sodium by itself).
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
GLP compliance:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 year
Frequency of treatment:
daily
Post exposure period:
not indicated
Remarks:
0, 0.1, 1, 5 or 10% in diet
No. of animals per sex per dose:
20/sex/group
Control animals:
yes, concurrent no treatment
Dose descriptor:
NOAEL
Effect level:
>= 10 other: %
Sex:
male/female
Basis for effect level:
other: no effects on tumor incidence.

A slight growth inhibition was observed at the 5% level and lethargy at the 10% level. Complete histopathological examination, including tumour incidences, was performed. No abnormalities or increased tumour incidence were found. The NOEL in this study was 1%, which corresponds to 370 mg of nitrate per kilogram of body weight per day

Conclusions:
NOEL = 1% (equivalent to 500 mg/kg bw/day).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The weight of evidence approach takes both available data (negative results) and the justification for the absence of data into account. Based on these data, sodium nitrate is not classified for carcinogenicity according to Annex I of Regulation (EC) No. 1272/2008.

Additional information

Several studies with sodium nitrate are available. The data are used in a weight-of-evidence approach, therefore no key study is selected. Published data were evaluated by WHO and IARC. It is concluded that there are no indications that sodium nitrate has carcinogenic properties.

Justification for selection of carcinogenicity via oral route endpoint:

No single study was selected as key study, the conclusion was derived based on weight-of-evidence.