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EC number: 231-793-3 | CAS number: 7733-02-0
Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not applicable
- 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:
- Effects of brief and intermediate exposures to sulfate submicron aerosols and sulfate injections on cardiopulmonary function of dogs and tracheal mucous velocity of sheep
- Author:
- Sackner M A, Dougherty R L, Chapman G A, Cipley J, Perez D, Kwoka M, Reinhart M, Brito M and Schreck R
- Year:
- 1 981
- Bibliographic source:
- J Toxicol Environ Health 7:951-972
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Determination of pulmonary mechanics and hemodynamics in anesthetized dogs following breathing of Zinc sulphate as submicron aerosols.
- GLP compliance:
- no
- Test type:
- other: Cardiopulmonary study
- Limit test:
- no
Test material
- Reference substance name:
- Zinc sulphate
- EC Number:
- 231-793-3
- EC Name:
- Zinc sulphate
- Cas Number:
- 7733-02-0
- Molecular formula:
- H2O4S.Zn
- IUPAC Name:
- zinc sulfate
- Details on test material:
- - Name of test material: Zinc sulphate
- Substance type: Pure active substance
- Physical state: Submicron aerosol
Constituent 1
Test animals
- Species:
- dog
- Strain:
- other: Mongrel
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- other: Cuffed 8.5 French orotracheal tube
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: D-30 nebulizer system
- Exposure chamber volume: No data
- Method of holding animals in test chamber: Anesthetized with i.v. Sodium pentobarbital, 30 mg/kg of body weight, and placed in lateral position
- Source and rate of air: No data
- Method of conditioning air: No data
- System of generating particulates/aerosols: Aerosols were generated from solutions of reagent grade chemicals by using a D-30 nebulizer system. Droplets were dried to a relative humidity of 20-30 % by mixing with dry air, and their electrical charges were neutralized by an ionizing radiation source of Kr-85.
- Method of particle size determination: Measured with an Electrical Aerosol Analyzer (EAA) (Thermo Systems, Inc., St. Paul, Minn.)
- Treatment of exhaust air: No data
- Relative humidity: 20-30 %
TEST ATMOSPHERE
- Brief description of analytical method used: Aerosol concentrations were measured by a piezoelectric microbalance. The filters were 0.2 µm pore size Nucleopore filters, 47 mm in diameter, supported in a Gelman stainless steel holder. The volume of air sampled was measured by a wet-gas test meter downstream of the filter. Zinc sulphate concentrations were measured by a barium-perchlorate-thorin spectrophotometric titration method.
- Samples taken from breathing zone: No
TEST ATMOSPHERE
- Particle size distribution: 0.01-1 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): No data
- Analytical verification of test atmosphere concentrations:
- yes
- Remarks:
- Barium-perchlorate-thorin spectrophotometric titration method
- Duration of exposure:
- 7.5 - 240 min
- Remarks on duration:
- 0.1 and 1% concentrations for 7.5 min; 0.5% concentration for 240 min
- Concentrations:
- 0.1 % & 1 % for brief exposure study
0.5 % for intermediate exposure study - No. of animals per sex per dose:
- Five
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 3 h
- Frequency of observations:
- Brief exposure study:
In the first series of experiments, groups of five dogs breathed for 7.5 min aerosols generated from 0.1 % solutions of Zinc sulphate. Measurements of lung volume and mechanics were obtained before and at 5, 15, 30, 60, 120, and 180 min after termination of the aerosol exposure. After completion of these measurements, the animals breathed aerosols generated from 1 % solutions of these salts for 7.5 min. Measurements of lung mechanics were repeated 5, 15, and 30 min after termination of the second exposures.
In the second set of experiments exposures to aerosols generated from 0.1 % salt solutions were omitted, and only 7.5-min exposures to aerosols generated from 1 % solutions. Measurements of total respiratory resistance, static lung compliance, and functional residual capacity were performed before and at 5, 15, 30, 60, 120, and 180 min after aerosol exposure.
- Intermediate Exposure study:
Groups of five dogs breathed for 4 h aerosols generated from 0.5 % solutions of Zinc sulphate. In addition, a 0.5% mixture of equal parts of the sulfate salts was employed. Measurements of lung volume, breathing mechanics, and hemodynamics were made before, hourly during, and for 2 h after completion of the aerosol exposures.
- Necropsy of survivors performed: No
- Other examinations performed: Measurements of lung volume, total respiratory resistance, static lung compliance, and functional residual capacity, breathing mechanics and hemodynamics. - Statistics:
- Analysis of variance was performed according to the model of Lorenzen (1977)
Results and discussion
- Preliminary study:
- Not applicable
Effect levelsopen allclose all
- Sex:
- male/female
- Dose descriptor:
- other: Effect on cardiopulmonary and hemodynamic mechanics
- Effect level:
- 15.8 mg/m³ air (analytical)
- Exp. duration:
- 7.5 min
- Sex:
- male/female
- Dose descriptor:
- other: Effect on cardiopulmonary and hemodynamic mechanics
- Effect level:
- 8.3 mg/m³ air (analytical)
- Exp. duration:
- 4 h
- Mortality:
- No data
- Clinical signs:
- other: No significant alterations in total respiratory resistance, static lung compliance, functional residual capacity, specific total respiratory conductance, and specific lung compliance after breathing for 7.5 min aerosols from 0.1 and 1.0 % solutions of Zin
- Body weight:
- No data
- Gross pathology:
- No data
- Other findings:
- No data
Any other information on results incl. tables
Time (h) |
RRS (cm H2O/L.s) |
FRC (L/BTPS) |
CL (L/cmH2O) |
SCL (L/cm H2O.L) |
SGRS (L/s.cmH2O.L) |
Baseline +1 +2 +3 +4 +5 +6 |
1.7 (0.05) 1.8 (0.06) 2.0 (0.02) 1.9 (0.07) 2.0 (0.2) 1.8 (0.0l) 2.0 (0.1) |
0.48 (0.05) 0.50 0.03) 0.47 (0.05) 0.47 (0.04) 0.47 (0.05) 0.47(0.04) 0.48 (0.05) |
0.14 (0.02) 0.13 (0.01) 0.12 (0.01) 0.12 (0.009) 0.12 (0.02) 0.13 (0.02) 0.13 (0.02) |
0.32 (0.08) 0.26 (0.03) 0.30 (0.07) 0.28 (0.05) 0.29 (0.07) 0.30 (0.07) 0.30 (0.09) |
1.3 (0.2) 1.1 (0.08) 1.2 (0.2) 1.2 (0.2) 1.2 (0.2) 1.2 (0.1) 1.1 (0.1) |
Table 2. Effects of Zinc sulfate aerosol (0.5 % for 4 h followed by 2 h observation) on hemodynamics and arterial blood gases of anesthetized dogs a
Time (h) |
PPA (mm Hg) |
PSA (mm Hg) |
QP (L/min) |
HR (beats/min) |
SV (mL) |
pH |
pO2 (mm Hg) |
pCO2 (mm Hg) |
Baseline +1 +2 +3 +4 +5 +6 |
10.5 (0.3) 11.9 (1.4) 12.2 (0.03) 12.5 (0.5) 13.8 (1.1) 11.6 (0.8) 11.9(1.5) |
104 (2) 96 (5) 106 (5) 116 (4) 108 (0) 106 (1) 106 (1) |
2.78 (0.14) 2.99 (0.22) 2.80 (0.20) 2.93 (0.29) 2.49 (0.18) 2.56 (0.16) 3.06 (0.32) |
142 (8) 131 (9) 144 (13) 117 (10) 122 (7) 124 (5) 127 (6) |
20.1 (2.0) 21.6 (0.8) 20.7 (2.1) 24.4 (1.9) 20.9(1.4) 20.4 (0.8) 23.9 (1.9) |
7.50 (0.03) 7.46 (0.02) 7.47 (0.02) 7.48 (0.02) 7.51 (0.01) 7.51 (0.02) 7.49 (0.02) |
111 (5) 99.4 (4.3) 98.0 (6.6) 94.6 (5.3) 97.0 (6.5) 97.2 (3.5) |
22.6 (13) 30.0 (0.9) 29.7 (0.23) 28.6 (1.1) 28.1 (0.8) 25.1 (1.5) 27.4 (3.0) |
aValues are mean (SE).
PPA= mean pulmonary arterial pressure; PSA= mean systemic arterial pressure; OP=cardiac output; HR= heart rate; SV= stroke volume; pO2= arterial O2 tension; pCO2= arterial CO2 tension.
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this test, aerosol of the test material was considered not to have adverse cardiopulmonary effects in dogs.
- Executive summary:
A study was conducted on anesthetized dogs to evaluate the effect of test material submicron aerosol (upto 15.8 mg/m3 for 7.5 to 240 min) on cardiopulmonary mechanics.
Aerosols generated from 0.1 and 1% solutions of the test material were exposed to one test group for 7.5 min and aerosols from 0.5% solution were exposed to the other group for 4 h. Measurements of lung volume, total respiratory resistance, static lung compliance, and functional residual capacity, breathing mechanics and hemodynamics were performed following the exposure at different intervals.
Under the conditions of this test, aerosol of the test material was considered not to have adverse cardiopulmonary effects in dogs.
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