Sodium azide

Basic toxicokinetics

Administrative data

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

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Sodium azide

Author:

ACGIH (American Conference of Governmental Industrial Hygienists)

Year:

1991

Bibliographic source:

ISBN-13: 978-0936712963, Documentation of the Threshold Limit Values & Biological Exposure Indices, 6th ed, 1403-7

Reference 2

Reference Type:

review article or handbook

Title:

Recommendation from the Scientific Committee on Occupational Exposure Limits (SCOEL) for Sodium Azide

Author:

Anonymous

Year:

2008

Bibliographic source:

European Commission: Scientific Committee on Occupational Exposure Limits (SCOEL)

Reference 3

Reference Type:

publication

Title:

Sodium Azide: Bioavailability And Metabolism in Rats

Author:

Lee E.W.

Year:

1982

Bibliographic source:

Toxicologist Vol. 2(1), 24

Materials and methods

Objective of study:

toxicokinetics

Test guideline

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

Test material

Test material information

Constituent 1

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

Radiolabelling:

not specified

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

not specified

Duration and frequency of treatment / exposure:

frequency of treatment: presumably single dose

Doses / concentrations

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

Results and discussion

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.

Toxicokinetic / pharmacokinetic studies

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.

Metabolite characterisation studies

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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.