|
Sodium azide
CASRN 26628-22-8
Contents
0191
Sodium azide; CASRN 26628-22-8
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Sodium azide
File On-Line 03/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 03/01/1988
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Sodium azide
CASRN -- 26628-22-8
Last Revised -- 03/01/1988
The oral Reference Dose (RfD) is based on the assumption that thresholds exist
for certain toxic effects such as cellular necrosis. It is expressed in units
of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable
risk of deleterious effects during a lifetime. Please refer to the Background
Document for an elaboration of these concepts. RfDs can also be derived for
the noncarcinogenic health effects of substances that are also carcinogens.
Therefore, it is essential to refer to other sources of information concerning
the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
Clinical signs (e.g., NOAEL: 5 mg/kg/day 1000 1 4E-3
hunched postures) and converted to 3.57 mg/kg/day
reduced body weight mg/kg/day
Rat Oral Subchronic LOAEL: 10 mg/kg/day
Study converted to 7.14
mg/kg/day
NCI, 1981
*Conversion Factors: x 5 days/7 days
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
NCI (National Cancer Institute). 1981. Ninety-day subchronic toxicity test
with sodium azide in Fischer 344 rats. Study No. 5650.08, report submitted by
Microbiological Associates, Bethesda, MD.
NCI (1981) reported a 90-day gavage (distilled water) study with rats
(10/sex/group) exposed to 0, 1.25, 2.5, 5, 10 or 20 mg/kg sodium azide, 5
days/week. Nearly total mortality occurred at the 20 mg/kg dose over the
experimental period, but no deaths occurred at other doses. A trend in
reduced weight gain was seen in the 10 mg/kg group. Females exhibited
slightly elevated mean liver-to-body weights in all dosage groups, but the
statistical significance of this increase was not reported. Histopathologic
evaluations revealed lesions in the brain and lung of the high-dose rats that
died; however, no compound-related lesions were discerned in any surviving
rats. The only significant clinical signs of toxicity were hunched postures
among males in the two highest dosage groups and females in the 20 mg/kg
group. Thus, 5 mg/kg was considered a NOAEL. By applying an uncertainty
factor of 1000 to this NOAEL and by multiplying by 5 days/7 days to account
for continuous exposure, an RfD of 0.004 mg/kg/day or 0.2 mg/day for a 70-kg
person is derived.
Data regarding the effects of oral exposure of humans to sodium azide are
available, but limited. During investigations of the effects of metabolic
inhibition on cancer patients, it was observed that sodium azide lowered the
blood pressure of hypertensive but not normotensive individuals (Black et al.,
1954). This report further indicated that nine normotensive individuals,
including both individuals and cancer patients, experienced no "sustained
effect" on blood pressure from the ingestion of as much as 1.3 mg of sodium
azide, 3 times/day for 10 days (3.9 mg/day or 0.056 mg/kg/day for a 70-kg
man). In a separate study, Black et al. (1954) measured blood pressure 4-12
hours after the last dosage in 30 hypertensive patients treated orally with
0.5-1.3 mg sodium azide, 3 times/day for periods ranging from 7 days to 2.5
years; 25/30 patients sustained lowering of blood pressure towards
normotensive levels. Some patients developed an increased sensitivity to the
drug with repeated treatment, necessitating a reduction in dosage to 0.25 mg,
3 times/day (0-75 mg/day or 0.011 mg/kg/day). No evidence of damage to the
kidney, heart or liver was detected in routine clinical studies of the three
hypertensive patients who ingested sodium azide for 1-2.5 years. Despite
short duration of exposure (10 days), sodium azide at dosages up to 0.056
mg/kg/day did not produce altered blood pressure in normotensive subjects.
The limited information tends to support the rat NOEL of 3.57 mg/kg/day.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty of 1000 was applied; 10 for interspecies, 10 for
intraspecies, and 10 for extrapolating from subchronic to chronic exposure.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
Sodium azide is a metabolic inhibitor that interferes with oxidative enzymes
and inhibits phosphorylation. A characteristic effect of acute administration
of sodium azide to experimental animals is hypotension (Reinhardt and
Britelli, 1982). Sodium azide is currently undergoing testing for chronic
oral toxicity in rats (NTP, 1985).
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- Medium
RfD -- Medium
The critical study is a well-designed subchronic study that defined both the
NOEL and LOAEL and was supported by range-finding studies; thus, a medium
confidence was assigned. The data base contained supportive animal and human
subchronic studies, buy lacks chronic and reproductive toxicity studies; thus,
the data base is rated medium. Medium confidence in the RfD follows.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- None
Agency Work Group Review -- 06/11/1986, 07/22/1986
Verification Date -- 07/22/1986
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Sodium azide
CASRN -- 26628-22-8
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Sodium azide
CASRN -- 26628-22-8
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- Sodium azide
CASRN -- 26628-22-8
Last Revised -- 01/01/1990
__VI.A. ORAL RfD REFERENCES
Black, M.M., B.W. Zweifach and F.D. Speer. 1954. Comparison of hypotensive
action of sodium azide in normotensive and hypertensive patients. Proc. Soc.
Exp. Biol. Med. 85: 11-16.
NCI (National Cancer Institute). 1981. Ninety-day subchronic toxicity test
with sodium azide in Fischer 344 rats. Study No. 5650.08, report submitted by
Microbiological Associates, Bethesda, MD.
NTP (National Toxicology Program). 1985. Management Status Report. 8/7/85
Reinhardt, C.F. and M.R. Britelli. 1982. Heterocyclic and miscellaneous
nitrogen compounds: Azides. In: Patty's Industrial Hygiene and Toxicology.
Vol. 2., 3rd ed., G.D. Clayton and F.E. Clayton, Ed. John Wiley and Sons,
Inc., New York. p. 2778-2822.
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Sodium azide
CASRN -- 26628-22-8
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
01/01/1990 VI. Bibliography on-line
01/01/1992 I.A.7. Primary contact changed
01/01/1992 IV. Regulatory actions updated
VIII. SYNONYMS
Substance Name -- Sodium azide
CASRN -- 26628-22-8
Last Revised -- 03/31/1987
26628-22-8
AZIDE
AZIUM
AZOTURE DE SODIUM
KAZOE
NATRIUMAZID
NATRIUMMAZIDE
NCI-C06462
NSC 3072
RCRA WASTE NUMBER P105
SMITE
Sodium Azide
SODIUM, AZOTURE DE
SODIUM, AZOTURO DI
U-3886
UN 1687
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0191.HTM
|
