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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic information given

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium nitrite
EC Number:
231-555-9
EC Name:
Sodium nitrite
Cas Number:
7632-00-0
Molecular formula:
HNO2.Na
IUPAC Name:
sodium nitrite
Details on test material:
sodium nitrite

Test animals

Species:
rat
Sex:
male

Administration / exposure

Route of administration:
oral: drinking water
Duration of treatment / exposure:
2 years
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 1000, 2000, 3000 mg/l (0, 10, 100, 250 or 350 mg/kg bw/day)
Basis:
nominal in water
No. of animals per sex per dose:
8
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
Body weight; once a month
Sacrifice and pathology:
Mortality; Methemoglobin; Blood chemistry; glucose, pyruvate, lactate
Pathology; heart, lungs, kidneys, liver, spleen, pancreas, adrenals and some brains.

Results and discussion

Results of examinations

Details on results:
There were no significant differences in growth, development, mortality or total haemoglobin levels between the control and treated groups. However, the methaemoglobin levels in the groups receiving 100, 250 and 350 mg/kg bw/day sodium nitrite were raised significantly throughout the study and averaged 5, 12 and 22% of total haemoglobin, respectively.
The main histopathological changes occurred in the lungs and heart. Focal degeneration and fibrosis of the heart muscle were observed in animals receiving the highest dose of nitrite. The coronary arteries were thin and dilated in these aged animals, instead of thickened and narrow as is usually seen at that age. Changes in the lungs consisted of dilatation of the bronchi with infiltration of lymphocytes and alveolar hyperinflation. Such changes were observed in rats receiving 100, 250 and 350 mg/kg bw/day sodium nitrite.

Effect levels

Dose descriptor:
NOEL
Effect level:
10 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: (focal degeneration and fibrosis of the heart, dilatation of the bronchi with infiltration of lymphocytes and alveolar hyperinflation in lungs) equivalent to 6.7 mg NO2/kg bw/day.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The Joint FAO/WHO Expert Committee on Food Additives (JECFA) established an acceptable daily nitrite intake of 0 to 0.07 mg NO2/kg bw/day by applying a safety factor of 100 to this NOEL.

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