Sodium azide

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: Handbook data

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Objective of study:

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

In vivo: Sodium azide was orally administered to rats. Blood and tissue samples were obtained and analyzed for sodium azide.

In vitro: Sodium azide was incubated with homogenates of different organs. Subsequently residual sodium azide was quantified. Reaction reates were calculated.

GLP compliance:

no

Radiolabelling:

not specified

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: unspecified

Vehicle:

not specified

Duration and frequency of treatment / exposure:

frequency of treatment: presumably single dose

Dose / conc.:

40 mg/kg bw/day (nominal)

No. of animals per sex per dose / concentration:

no data

Control animals:

not specified

Positive control reference chemical:

no data

Preliminary studies:

Previous investigation (Toxicologist 1, 21-22) reported the absence of azide in blood and lack of toxicity of the daily dose of 23 mg/kg sodium azide in drinking water for 90 or 147 days in laboratory rats.

Details on absorption:

Sodium azide was detected in rat plasma 5 minutes after a single oral dose of 40 mg/kg. The calculated rate of sodium azide absorption from the gastrointestinal tract after intake of 23 mg/kg/day was equivalent only to 0.0162 mg/kg/min.

Details on distribution in tissues:

After 24 h, no azide could be detected in either blood or peripheral tissues.

Details on excretion:

A small fraction of the administered dose (7.9 µg) was eliminated in rat 24h urine, but no azide was detected in expired air or feces.

Metabolites identified:

yes

Details on metabolites:

Sodium azide is mainly metabolised in the liver with nitric oxide as main metabolite. Incubation with different (unspecified) organ homogenates exhibited no azide decomposition except for liver homogenate.
Sodium azide penetrates the blood-brain barrier. Azide anions may be metabolised to nitric oxide (NO) also in the CNS. In aqueous solution (e.g. blood), it rapidly transforms into hydrazoic acid (CAS no. 7782-79-8), which may be responsible for the irritating effects attributed to sodium azide.

Sodium azide was detected in the plasma as early as 5 min after the oral adminstration. No azide was identified in both plasma and tissues 24 hours later. During the same period, no azide was excreted in the feces or exhaled in the air. Only 7.9 µg of azide was excreted in the urine. Rat liver was found as the organ responsible for the deactivation of azide since in the invitro study, the liver homogenate rapidely destroyed sodium azide, whereas homogenates of other tissues did not and the azide absorbed from the gastrointestinal tract was metabolized as soon as it reached the liver. At the maximum reaction rate, one mL of 20% liver homogenate metabolized 1.13 µg sodium azide per minute. A peak level of azide in plasma, 49 µg/mL was detected after a 40 mg/kg bw dose but no azide was found in the plasma with a bolus dose of 0.38 mg/kg bw. Trace amounts were detected with 0.75 mg/kg bw. This indicated that a single oral dose of 0.38 mg/kg bw does not exceed the metabolic capacity of the liver. Also, since the oral administration required less than 10 seconds for the appearance of azide in the plasma, the calculated rate of sodium azide absorption from the gastrointestinal tract after intake of 23 mg/kg/day was equivalent only to 0.0027 mg/kg/10 sec. This intake rate is well below the metabolizing capacity of the rat liver tissue, and it is therefore not suprizing that no azide was detected in the plasma and no hematological or histopathological abnormalities were observed in the experimental animals with this dose level.

Conclusions:

Based on the presented data, sodium azide showed no bioaccumulation potential.

Executive summary:

Sodium azide was detected in rat plasma 5 minutes after a single oral dose of 40 mg/kg bw. After 24 hours, no azide could be detected in either blood or peripheral tissues. A small fraction of the administered dose (7.9 µg) was eliminated in rat 24 h urine, but no azide was detected in expired air or feces. Sodium azide is reported to be quickly absorbed from injection sites and from the respiratory tract. Sodium azide is mainly metabolized in the liver. The main metabolite in the liver is nitric oxide (CAS 10102-43-9). Sodium azide also penetrates the blood-brain barrier and may serve as a source of nitric oxide (NO) also in the CNS. In aqueous solution, it rapidly transforms into hydrazoic acid (CAS no. 7782-79-8), which may be responsible for the irritating effects attributed to sodium azide.

Reference 2

Endpoint:

basic toxicokinetics

Type of information:

other: Handbook

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Objective of study:

excretion

Qualifier:

no guideline available

GLP compliance:

not specified

Radiolabelling:

not specified

Species:

human

Strain:

not specified

Sex:

not specified

Route of administration:

other: no data

Vehicle:

not specified

Duration and frequency of treatment / exposure:

no data

No. of animals per sex per dose / concentration:

no data

Control animals:

not specified

Details on excretion:

half-live: 2.5h

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 2.5h

Metabolites identified:

not specified

Sodium azide is rapidely absorbed from the gastrointestinal and respiratory tracts (as hydroazoic acid vapour). Its extent of dermal absorption is unclear. Sodium azide is metabolized by the liver and excreted by the kidneys, but human absorption, distribution, metabolism and excretion kinetics data are not available, except for a half-life of about 2.5 hours calculated in a single fatal case (Senda T. et al., 2001. Chudoku Kenkyu 14, 339).

Conclusions:

Sodium azide is rapidely absorbed from the gastrointestinal and respiratory tracts (as hydroazoic acid vapour). Its extent of dermal absorption is unclear. Sodium azide is metabolized by the liver and excreted by the kidneys, but human absorption, distribution, metabolism and excretion kinetics data are not available, except for a half-life of about 2.5 hours calculated in a single fatal case.

Executive summary:

Sodium azide is rapidely absorbed from the gastrointestinal and respiratory tracts (as hydroazoic acid vapour). Its extent of dermal absorption is unclear. Sodium azide is metabolized by the liver and excreted by the kidneys, but human absorption, distribution, metabolism and excretion kinetics data are not available, except for a half-life of about 2.5 hours calculated in a single fatal case.

Description of key information

Sodium azide is rapidly absorbed following ingestion and metabolized completely in the body as exemplified by the lack of presence of the parent compound in the faeces or exhaled air. Metabolism occurs mainly in the liver with some reports of metabolism also taking place in the brain following penetration of the blood brain barrier. Metabolism leads to the formation of nitric oxide as the main metabolite in the liver and in the brain. Sodium azide is excreted by the kidneys, but human absorption, distribution, metabolism, and excretion kinetics data are not available. There has been a report of a half-life of about 2.5 hours calculated in a single fatal case in human.

The main metabolite in the liver is nitric oxide (CAS 10102-43-9). Sodium azide also penetrates the blood-brain barrier and may serve as a source of nitric oxide (NO) also in the CNS. In aqueous solution, it rapidly transforms into hydrazoic acid (CAS no. 7782-79-8), which may be responsible for the irritating effects attributed to sodium azide.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential