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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-05-16 to 2009-12-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
1998
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
no

Test material

Constituent 1
Chemical structure
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
Specific details on test material used for the study:
- Lot: #C-07A005 and #C-08V701
- Composition: >95% pure
- Physical appearance: White solid, similar in appearance to typical table salt
- pH: 9+
- Solubility: Soluble in water
- Stability: Test substance was expected to be stable for the duration of testing
- Expiration Date: Not Applicable
- Treatment of the test material prior testing: Prior to aerosolization, the test substance was ground in a ball mill for 24 hours and then further ground in a coffee mill (Cuisinart, Model #DC0-20) until it passed through a 425 micrometer sieve (USA standard).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult (9-10 weeks) /
- Weight at study initiation: males 280-338 grams and females 190-236
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Purina Rodent Chow #5012
- Water (e.g. ad libitum): Yes
- Acclimation period: 14-18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24°C
- Humidity (%): 66-79%
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
> 3.5 - < 3.7 µm
Geometric standard deviation (GSD):
> 1.88 - < 2.16
Remark on MMAD/GSD:
The aerodynamic mass median diameter and geometric standard deviation were determined graphically using two-cycle logarithmic probit axes.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Mini-Nose Only Inhalation Chamber by ADG Developments LTD
- Exposure chamber volume: 6. 7 L
- Method of holding animals in test chamber: Polycarbonate holding tubes which seal to the chamber with an "O" ring during exposure.
- Source of air: Air compressor by JUN-AIR
- System of generating particulates/aerosols: Wright Dust Generator driven by a variable speed motor by Dayton
- Method of particle size determination: Eight-stage Andersen cascade impactor

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: An eight-stage Andersen cascade impactor was used to assess the particle size distribution of the test atmosphere. Samples were withdrawn from the breathing zone of the animals at two intervals. The filter paper collection stages were weighed before and after sampling to determine the mass collected upon each stage.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The aerodynamic mass median diameter and geometric standard deviation were determined graphically using two-cycle logarithmic probit axes. See table 1 under "Any other information on materials and methods incl. tables"
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
See table 1 under "Any other information on materials and methods incl. tables"
No. of animals per sex per dose:
5 males and 5 females per dose/ 3 doses
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: Prior to exposure and again on Days 7 and 14 or after death
- Frequency of observation: At least once daily for up to 14 days following exposure or until death occured
- Necropsy of survivors performed: yes
- Examinations performed: mortality, signs of toxicity, behavioral changes, body weight
Statistics:
Mean + / - Standard Deviation

Results and discussion

Preliminary study:
See table 1 under "Any other information on materials and methods incl. tables"
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.054 - < 0.52 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
- At 2.02 mg/L exposure level, all animals died within 190 minutes of exposure to the test atmosphere
- At 0.52 mg/L exposure level, four male and four female rats died during exposure to the test atmosphere
- At 0.0542 mg/L exposure level, no mortality was observed
Clinical signs:
other: - At 0.52 mg/L exposure level, the surviving animals were hypoactive and exhibited hunched posture, abnormal respiration and nasal discharge - At 0.0542 mg/L exposure level, all animals exhibited ocular and nasal discharge.
Body weight:
- At 0.52 mg/L exposure level, all surviving animals recovered by Day 3, gained body weight and appeared active and healthy for the remainder 14-day observation period.
- At 0.0542 mg/L exposure level, body weight was shown to increase over the observation period
Gross pathology:
- At 2.02 mg/L exposure level, gross necropsy of the decedents revealed red, edematous lungs, normal trachea and clear wet nasal discharge.
- At 0.52 mg/L exposure level, gross necropsy of the decedents revealed red, edematous lungs, normal trachea and clear wet nasal discharge. No gross abnormalities were noted for the euthanized animal when necropsied at the conclusion of the 14-day observation period.
- At 0.0542 mg/L exposure level, no gross abnormalities were observed

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
In conclusion, the acute inhalation toxicity of Sodium azide, as determined in a study according to EPA guideline OPPTS 870.1300, lies between an LC50 (4 h) of 0.054 and 0.52 mg /L in male and female rats.
Executive summary:

In an acute inhalation toxicity study according to EPA guideline OPPTS 870.1300, groups of young adult Sprague Dawley rats (5/sex) were exposed at test concentrations of 0.054, 0.52 and 2 mg/L via the inhalation route (nose only) to Sodium azide (>95% purity) in compressed air for 4 hours. After exposure, the animals were observed for a period of 14 days. At test concentration of 0.52 and 2.0 mg/L, mortality was observed. An increase in body weight was seen at 0.54 mg/L and gross pathology at test concentrations 0.52 and 2 mg/L revealed red, edematous lungs, normal trachea and clear wet nasal discharge. Thus, under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is between 0.054 and 0.52 mg/L in male and female rats.