Sodium azide

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1996

Materials and methods

Study type:

health record from industry

Remarks:

NIOSH study of complaints by workers

Endpoint addressed:

acute toxicity: inhalation

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Cross-sectional study of health complaints reported by sodium azide production workers. The evaluation consisted of a plant industrial hygiene survey, a symptom questionnaire, ambulatory blood pressure monitoring, and blood azide analysis.

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

Method

Type of population:

occupational

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

Medical Evaluation
The medical evaluation (performed over two consecutive 12-hr shifts) consisted of symptoms questionnaires, ambulatory blood pressure monitoring (ABPM), and blood azide analysis. All production operators working at the time of our site visit were asked to participate in the evaluation. Employees were informed of the evaluation by both management and NIOSH personnel and provided signed informed consent prior to participating. A symptom (including specific questions concerning headache, lightheadedness, rapid heartbeat, and eye irritation) and work history questionnaire was administered to all participants at the start of the work shift, and brief symptom questionnaires were administered throughout the work shift.

Blood Pressure Monitoring
Blood pressure was monitored with the use of ambulatory blood pressure monitors (Advanced Medical Products, model 5600, Columbia, SC). Participants were asked to wear the monitor for one of their usual 12-hr shifts and to activate the monitor at least every 30 min by pressing a button. The first three manual blood pressure measurements, taken with the standard sphygmomanometer while the participant had been seated for at least 5 min, were averaged and used as the participant's baseline blood pressure. A hypotensive episode during the work shift was defined as a drop from baseline of 20 mm Hg in systolic blood pressure (SBP) and of 10 mm Hg in diastolic blood pressure (DBP). In addition, for men, a blood pressure of 90/60 or lower would be considered hypotensive; a blood pressure of 80/50 or lower would be considered hypotensive for women. The blood pressure data were analyzed by evaluating the blood pressure changes per individual, the means of the blood pressures of the individuals in the control room versus those in the production areas, and the grouped means of blood pressures in the control room versus those in the production areas.

Blood Azide Monitoring
Two blood samples, a pre-shift sample and a sample during work (after potential exposure to Sodium azide), were collected from participants and immediately frozen. The samples were analyzed for azide content using a high-pressure ion chromatography method [Smith RP et al., Fund App Toxicol 1991, 17:120-127]. Twenty-seven quality-control samples (nine known concentrations in triplicate) were prepared in human blood in the NIOSH laboratory, immediately frozen, and sent to a contract laboratory with the field samples (Dartmouth Medical School, Department of Pharmacology and Toxicology, Hanover, NH). The quality control samples were prepared over a range of 0-6000 parts per billion (ppb) of Sodium azide, based on the estimated levels of Sodium azide in the blood after a presumed occupational exposure. Because this method for azide analysis had not previously been validated in humans, NIOSH investigators applied for and received approval from the NIOSH Human Subjects Review board to perform this biomonitoring.

Results and discussion

Results:

Exposure Assessment
Area sampling results ranged from not detected (ND) to 0.69 mg/m3 for sodium azide, and from ND to 0.07 ppm for hydrazoic acid.
Seven (25%) of the 28 sodium azide PBZ air concentrations (total particulate and vapor azide concentrations) exceeded the NIOSH REL of 0.3 mg/m3 (ceiling limit). Four (14%) of the 28 PBZ air concentrations of hydrazoic acid exceeded, or equaled, the NIOSH REL of 0.1 ppm (ceiling limit).
Three sets of PBZ samples were collected to compare sodium azide and Hydrazoic acid concentrations inside and outside of the air-line respirators. Particulate sodium azide was not detected in any of the samples inside the hoods of the air-line respirators. In each set of samples, however, hydrazoic acid was detected inside the hood. In fact, hydrazoic acid concentrations inside the hoods of the respirators were greater than the corresponding concentrations sampled outside the hood in two of the three pairs.

Medical Evaluation
The participants included 10 men and one woman; their mean age was 33 years (range 27-42). None of the participants reported a history of high blood pressure or any medication use. The most common symptoms reported by the 11 participants while working in the production areas during the 6 months prior to our evaluation included headache (10 persons [91%]) and increased heart rate or palpitations (9 persons [82%]). Nine of the 11 participants reported at least one instance during the preceding 6 months of "low" blood pressure occurring after working in a production area, ranging from 77/40 to 102/40. During our medical evaluation, four workers reported mild headaches after working in the production areas.

Blood Pressure Monitoring
A total of 160 blood pressure measurements were attempted by the ten participants. Of these, in 110 (69%) a blood pressure was recorded by the ABPM. One employee met our criteria for a hypotensive episode during a work shift when the blood pressure dropped from a baseline of 119/81 to readings of 111/76, 99/62, and 98/66, the last two measurements taken at 1 and 1.5 hr, respectively, after the baseline pressure was taken (ABPM was discontinued at the employee's request as he finished this work task). PBZ air sampling performed 1 hr after the last blood pressure measurement revealed concentrations of sodium azide and hydrazoic acid of 1.7 mg/m3 and 0.06 ppm, respectively. The employee reported no symptoms throughout the work shift (including after monitoring ended). A blood pressure taken manually 1 hr after the monitoring ended, while the employee was on break, revealed a blood pressure of 116/78.
For seven individuals, we found no significant differences in employees' mean blood pressures in the control room versus employees' mean blood pressures in the production area (Student's t-test, level of significance p < 0.05). Similarly, the grouped mean of blood pressure in the control room was not significantly different from that in the production areas.

Biological Monitoring
Ten participants provided blood samples. Analysis of the quality control samples revealed an analytical limit of detection (LOD) of 2,800 ppb azide, with 47% recovery above the LOD. None of the participants' blood had detectable quantities of azide.

Applicant's summary and conclusion

Conclusions:

Exposure of sodium azide leads to health complaints (headache, changes in blood pressure, palpilations etc.) in sodium azide production workers working in a sodium azide production facility.

Executive summary:

In 1994-1995, the National Institute for Occupational Safety and Health (NIOSH) conducted a cross-sectional study of health complaints reported by sodium azide production workers at the only continuous sodium azide production facility in the United States. The NIOSH evaluation consisted of a plant industrial hygiene survey, a symptom questionnaire, ambulatory blood pressure monitoring, and blood azide analysis. Personal breathing zone air monitoring revealed exposures to sodium azide and hydrazoic acid (a reactant product) at levels greater than the NIOSH Recommended Exposure Limits (RELs). In some cases, exposures exceeded the REL despite the use of air-supplied respirators. The questionnaire revealed that most workers reported headache (10 of 11 [91%]), episodes of low blood pressure (9 of 11 [82%]), and palpitations (8 of 11 [73%]) occurring in the production areas within the 6 months preceding the study. Mild headache (4 of 11 [36%]) was the only symptom reported during our 24-hr medical survey. Ambulatory blood pressure monitoring revealed one asymptomatic employee with a drop-in blood pressure (defined as a drop in systolic [at least 20 mm Hg] and diastolic [at least 10 mm Hg] blood pressure) during a period of exposure to sodium azide at a level five times the NIOSHREL. Improvements in plant engineering controls, increased attention to employee hygiene practices, and a more comprehensive respiratory protection program were recommendations made by NIOSH to reduce exposures at the plant. All facilities handling sodium azide should be aware of the potential toxicity of sodium azide and hydrazoic acid.