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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only lung, trachea and bronchial lymphnodes examined histopathologically, only one dose tested.

Data source

Reference
Reference Type:
publication
Title:
Toxicology of Ammonium Sulfate in the Lung.
Author:
Pepelko WE et al.
Year:
1980
Bibliographic source:
Bull Environ Contam Toxicol 24: 156-160.

Materials and methods

Principles of method if other than guideline:
no data
GLP compliance:
not specified
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium sulphate
EC Number:
231-984-1
EC Name:
Ammonium sulphate
Cas Number:
7783-20-2
Molecular formula:
H3N.1/2H2O4S
IUPAC Name:
Monochloramine generated from ammonium sulphate and a chlorine source
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
young adult male rats
- Weight at study initiation: mean weights: 435 +/- 20 g (control animals), 447 +/- 17 g (test animals)
- Housing: 2 per cage in 28-cn (11-inch) square wire cages
- Diet: ad libitum
- Water: ad libitum
No further data.

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: water
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Ammonium sulfate aerosol was generated from an aqueous solution with either one or two Retec nebulizers (Retec Development Laboratory, Portland, Oregon) and dried by mixing with dry air and passing it through a heated glass tube. Two nebulizers were used at concentrations greater than 500 mg/m³. Ammonium sulfate concentration was determined by collecting the aerosol on a Gelman A- E glass fiber filter at a flow rate of 2 l/min for 15 min and weighing the filter. Accuracy of the method was periodically checked by chemical analysis of the filter sample. Particle size was evaluated gravimetrically using an Andersen multi-stage sampler (Andersen Sampler Inc., Atlanta, Georgia).
No further data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
For description of the method, see above (Details on exposure)
Result of the atmosphere analysis: Particle size averaged approximately 1-2 µm diameter at 300 mg/m³. Concentrations of ammonium sulfate during exposures were maintained within +/- 10% of the desired concentration.
Duration of treatment / exposure:
1, 3, 7, or 14 days
Frequency of treatment:
8 hours per day
Doses / concentrations
Dose / conc.:
300 mg/m³ air (analytical)
No. of animals per sex per dose:
10 males per group
Control animals:
yes
Details on study design:
- Dose selection rationale:
The concentrations used were determined on basis of the results from a preliminary study with rats were exposed to the maximum attainable concentration of ammonium sulfate using the same equipment and methods, i.e. a group of 6 male rats were exposed 8 h/day for 3 consecutive days to a concentration of 1000-1200 mg/m3. No toxicological effects were noted in this pretest.

Results and discussion

Effect levels

Key result
Dose descriptor:
NOAEC
Effect level:
ca. 300 mg/m³ air
Sex:
male
Basis for effect level:
other: only one concentration tested, only lung, trachea and bronchial lymphnodes examined histopathologically.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Arterial Blood Measurements after 1, 3, 7, 14 days exposure to 300 mg/m3 Ammoniumsulfate (N=10 for all groups). Arterial blood gases, pH, and bicarbonate of rats exposed 1, 3, 7 or 14 days are shown in Table 1. No significant differences could be detected between control and exposed rats for any of the parameters measured.

    Arterial PO2 (Torr)

    Arterial PCO2 (Torr)

     control exposed  control  exposed 
  days exposure        
 1 94 ± 4 96 ±  37 ± 3 36 ±
 3 96 ± 2 91 ± 36 ± 36 ±
 7 93 ± 3 96 ± 34 ± 33 ±
 14 89 ± 94 ± 37 ± 36 ±
         
        Arterial pH Standard Bicarbonate (MM/L)    
 7.47 ± 0.03 7.45 ± 0.04  28.6  ± 2.4  27.6  ± 4.4 
 3   7.46 ± 0.02   7.46 ± 0.03   26.6  ± 0.8  28.6  ± 3.1
 7   7.47 ± 0.02    7.49 ± 0.04   27.4  ± 1.1   26.5 ± 1.6 
14     7.47 ± 0.01   7.45 ± 0.03    27.4  ± 2.6  26.7  ±0.8  

Table 2: Repeated body weight measurements, vital capacity residual volume and wet lung weights of rats exposed 14 days to 300 mg/m3 ammonium sulfate (N=for all groups). Body weights, VC, RV and wet lung weights of rats exposed 14 days to 300 mg/m³ ammonium sulfate are shown in Table 2. Again, none of these parameters were significantly affected by exposure. Histological examination of the trachea, bronchial lymph nodes and lungs revealed no changes that could be definitely attributed to exposure.

     Control  Exposed
 body weight pre-exposure  (GMS)  435 ± 20   447 ± 17 
 body weight 1 day   (GMS)    420 ± 15   437 ± 21 
 body weight 3 day   (GMS)   432 ± 17    441 ± 20 
 body weight 7 day   (GMS)    442 ± 20    445 ± 18
 body weight 14 day   (GMS)    457 ± 22   446 ± 17 
 vital capacity   (CC) 17.1 ± 2.0  16.6 ± 1.9 
 residual volume   (CC) 1.92 ± 0.26 1.75 ± 0.26 
 wet lung weight   (GMS)  2,12 ± 0.41 2.11 ± 0.17 

The authors concluded that inhaled ammonium sulfate is relatively non-toxic except at very high concentrations. They also concluded that any concentration of sulfuric acid likely to be present in the atmosphere is probably non-toxic since the chances of neutralization to ammonium sulfate in the respiratory tract is very great.

Applicant's summary and conclusion