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EC number: 247-852-1 | CAS number: 26628-22-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Neurotoxicity
Administrative data
- Endpoint:
- neurotoxicity: chronic oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP study, comparable to OECD guideline with acceptable restrictions
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1991
- Reference Type:
- review article or handbook
- Title:
- Weight of Evidence Discussion for Sodium Azide (NaN3)
- Author:
- Mc Carroll N.
- Year:
- 2 007
- Bibliographic source:
- US Environmental Protection Agency (EPA) Memorandum TXR 0054719
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 453
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Sodium azide
- EC Number:
- 247-852-1
- EC Name:
- Sodium azide
- Cas Number:
- 26628-22-8
- Molecular formula:
- N3Na
- IUPAC Name:
- sodium azide
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Sodium azide
- Substance type: powder
- Physical state: solid
- Analytical purity: >99%
- Lot/batch No.: 32880
- Stability under test conditions: stable for at least two weeks at up to 60°C
- Storage condition of test material: in the dark at room temperature
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston NY
- Age at study initiation: 48-55 days
- Weight at study initiation: 153-156 g
- Fasting period before study: no data
- Housing: % Animals per cage in polycarbonate cages with Hardwood chips, changes twice a week. Spun-bound polyester cage filter sheets and stainless steel racks were changed every two weeks.
- Diet (e.g. ad libitum): NIH-07 Rat and Mouse Ration (Zeigler Bros. Inc. Gardners PA), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: quarantine for 19 days before start of the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-79 °F (20-26 °C)
- Humidity (%): 10-84%
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The required amount of Sodium azide for each concentration was transferred to the appropriately sized volumetric flask. The flask was filled to approximately 3/4 volume with distilled wate, stoppered and shaken until throroughly mixed. The flask was then filled to volume with water, using a pipette to carefully add the last few milliliters, stoppered, mixed and transferred to the appropriate dosing bottles.
DIET PREPARATION
- Maximum storag time for feed: 120 days - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The study laboratory conducted periodic analyses of the sodium azide dose formulations using a titrimetric procedure. The dose formulations were analyzed at approximately 8-week intervals and were within ±10% of the target concentrations 100% of the time. Results of periodic referee analyses by the analytical chemistry laboratory agreed with the results from the study laboratory.
- Duration of treatment / exposure:
- 5 days per week (excluding weekends) for a total of 103 weeks.
- Frequency of treatment:
- 5 days per week (excluding weekends) for a total of 103 weeks.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 5 mg/kg bw/day (nominal)
- Dose / conc.:
- 10 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 60 rats per sex per dose group
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and clinical examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule: Body weights per cage were recorded once per week for the first 13 weeks of the studies, during weeks 17 and 19, and from weeks 21 to 31, and every 2 to 5 weeks thereafter. Mean body weights were calculated for each group. - Sacrifice and (histo)pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes , examined tissues are listed in the Table below.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Of rats receiving 10 mg/kg, 49/60 males and 53/60 females became very lethargic after dosing at some time during the studies. In comparison, lethargy was observed in eight control males, eight low-dose males, four control females, and six low-dose females. Four male and four female rats receiving 10 mg/kg and one male receiving 5 mg/kg Sodium azide convulsed at the time of dosing, and five high-dose males, eight high-dose females, and two low-dose females became comatose for 1 to 2 hours. Many of these animals died within 3 to 5 days following the appearance of these clinical findings. These early deaths were attributed to the brain necrosis found upon microscopic examination of brain tissue sections from these animals. Additional clinical findings in high-dose rats included recumbency (males, 22/60; females, 5/60), rough hair (males, 60/60; females, 53/60), emaciation (females, 29/60), and toe-walking (males, 11/60; females, 51-60).
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Survival was substantially reduced in high-dose males and females. Brain necrosis, most notably in the cerebrum and thalamus, was a major cause of mortality in high-dose male and female rats and was attributed to the toxicity of Sodium azide. The lower than usual survival rate (less than 50%) of the control and low-dose male rats was probably due to the high incidence of mononuclear cell leukemia in these groups.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean body weights of male and female rats receiving Sodium azide were consistently lower than those of controls throughout the studies. After 24 weeks, the mean body weights of high-dose male and female rats were notably lower than those of the control animals.
- Food consumption and compound intake (if feeding study):
- not examined
- Description (incidence and severity):
- High-dose males consistently consumed less feed than control males. High-dose females consumed considerably less feed than control females between week 16, when feed consumption measurements were initiated, and week 56. After week 56, feed consumption by high-dose females was still below that of controls, but to a smaller margin than seen previously. Mean feed consumption values for low- and high-dose rats were lower than control values.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- A high incidence of brain necrosis was observed in the high-dose males and females. The brain lesions were often of sufficient severity to result in the death of the affected animals. The high-dose animals also had an increased incidence of pulmonary congestion, sometimes with hemorrhage, which was considered to be a secondary effect of brain necrosis.
Brain:
The significant treatment-related finding in the brain was necrosis of the cerebrum, thalamus, or both. This lesion was observed in a large percentage of the high-dose males and females. There was a single occurrence of cerebral necrosis in a low-dose male and a low-dose female and a single occurrence of thalamic necrosis in a low-dose male. These lesions were not observed in control animals.
The brain lesions were usually bilaterally symmetrical. Cerebral necrosis occurred at a specific subcortical site, apparently in the region of the caudate-putamen basal ganglia. Three high-dose females with cerebral necrosis also had necrosis of the hippocampus, a deep portion of the cerebral cortex. Thalamic necrosis was usually localized either in the dorsal region of the thalamus, just ventral to the hippocampus, or in the center of the thalamus. One high-dose male had necrosis in the pons, a portion of the brainstem caudal to the thalamus. The areas of necrosis varied in size, and the severity of necrosis ranged from acute to chronic.
Acute lesions consisted of necrosis of neurons that was often accompanied by necrosis of elements of the neuropil. Necrotic cells had deeply eosinophilic cytoplasm with pyknotic or karyorrhectic nuclei. Inflammatory cell infiltrate was minimal or absent from acute lesions.
Chronic lesions were characterized by the loss of neurons and neuropil, infiltration of macrophages, and proliferation of glial cells and blood vessels. Acute and chronic lesions were often seen in the same animal. - Histopathological findings: neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Only a few neoplasms of the brain were found in these studies. A single glioma occurred in a high-dose male, an oligodendroglioma in one low-dose female, and a single astrocytoma in a high-dose female. A granular cell tumor, presumably of meningeal cell origin, occurred in one high-dose male. None of these neoplasms was considered to be treatment related.
- Other effects:
- not examined
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 5 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- histopathology: non-neoplastic
- mortality
- Dose descriptor:
- LOAEL
- Effect level:
- 10 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- histopathology: non-neoplastic
- mortality
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 10 mg/kg bw/day
- System:
- central nervous system
- Organ:
- brain
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- From the given data, a NOAEL of 5 and a LOAEL of 10 mg/kg bw can be derived.
- Executive summary:
Sodium azide was nominated by the National Cancer Institute for evaluation of its carcinogenic activity because of the high potential for human exposure and the lack of adequate carcinogenicity testing. Sodium azide (>99% pure) was administered orally. Because Sodium azide is unstable in feed formulations, the compound was administered by gavage.
Two-year studies were conducted by administering 0, 5, or 10 mg/kg Sodium azide to groups of 60 male and 60 female rats. Dose-related depression in mean body weight was observed throughout the study period. Mean feed consumption values in low and high-dose groups were lower than control values. Survival of high-dose rats of each sex was significantly (P<0.05) lower than controls (males: control, 24/60; low-dose, 27/60; high-dose, 9/60; females: 37/60; 43/60; 21/59). The reduced survival was mainly attributed to brain necrosis, particular prominent in the caudate nucleus and the putamen.
From the given data a LOAEL of 10 mg/kg bw and a NOAEL of 5 mg/kg bw for neurotoxicity can be derived.
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