Registration Dossier

Administrative data

Description of key information

Ammonium sulfate is of relatively low acute toxicity (LD50, oral, rat: 2000 - 4250 mg/kg bw; LD50 dermal,

rat/mouse > 2000 mg/kg bw; 8-h LC50, inhalation, rat > 1000 mg/m³). Clinical signs after oral exposure included staggering, prostration, apathy, and laboured and irregular breathing immediately after dosing at doses near to or exceeding the LD50 value. In humans, inhalation exposure to 0.1 - 0.5 mg ammonium sulfate/m³ aerosol for two to four hours produced no pulmonary effects. At 1 mg ammonium sulfate/m³ very slight pulmonary effects in the form of a decrease in expiratory flow, in pulmonary flow resistance and dynamic lung compliance were found in healthy volunteers after acute exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Post exposure observation period only 7 days
Principles of method if other than guideline:
BASF Test.
In principle, the methods described by OECD TG 401 were used.
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Gassner
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gassner
- Weight at study initiation: mean weights: 131-148 g

ENVIRONMENTAL CONDITIONS: no data
No further data
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30%
Doses:
2500, 3200, 4000, 5000, 6400 mg/kg bw
No. of animals per sex per dose:
10 male and 1o females per group
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology
Statistics:
The LD50 was calculated according to the method described by Litchfield-Wilcoxon.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 250 mg/kg bw
95% CL:
3 788 - 4 769
Mortality:
Mortality and time of death(s) per dose group:
- 6400 mg/kg bw: 12 died within the first hour, 2 within 24 hours, 4 within 48 hours; in total, 18/20 died within 7 days.
- 5000 mg/kg bw: 8 died within the first hour, 1 within 24 hours, 1 within 48 hours; in total 11/20 died within 7 days.
- 4000 mg/kg bw: 7 died within 24 hours, and 2 within 48 hours; in total, 9/20 died within 7 days.
- 3200 mg/kg bw: 1 animal died within the first hour, 1 within 24 hours, 2 within 48 hours; in total, 4/20 died within 7 days.
- 2500 mg/kg bw: no deaths occurred.
Clinical signs:
- 4000-6400 mg/kg bw: immediately after application staggering, abdominal and lateral position, partly dorsal position, apathy, laboured and irregular breathing. On the next day, secretion out of eyes and mouth, reddened eyes and nose. In the post-exposure observation days the animals were without clinical symptoms.
- 3200 mg/kg bw: No symptoms on the application day. The next day, reddened eyes and nose, and irregular breathing were noted. Later without clinical signs.
- 2500 mg/kg bw: No clinical signs noted.
Gross pathology:
At necropsy, fluid in the thoracic cavity was observed in a few animals. In three animals, the stomach was filled with liquid, and bloody mouth and forelegs were noted. No pathological findings were noted with regard to the inner organs.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
not specified
Test type:
acute toxic class method
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
male and female Wistar rats
- Age at study initiation: 5-6 weeks
- Acclimation period: at least 5 days
no further data

ENVIRONMENTAL CONDITIONS: no data
Route of administration:
oral: gavage
Vehicle:
water
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical and behavioural abnormalities, body weight, mortality, gross lesions
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw

Based on the results of this test, the LD50 was >2000 mg/kg bw.

According to the authors, this agreed well with literature data: LD50: 3000 - 4000 mg/kg bw [Frank JF (1948). The toxicity of sodium chlorate herbicides. Can J Comp Med 12: 216 -218].

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 250 mg/kg bw
Quality of whole database:
OECD TG 401

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 433 draft (Acute Inhalation Toxicity: Fixed Concentration Procedure) (not officially approved)
GLP compliance:
not specified
Test type:
other: effect on respiratory defense system
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
male SPF Sprague-Dawley rats
- Source: Hilltop Lab Animals, Inc. (Chatsworth, Calif.)
- Weight at study initiation: ca. 200 g
No further data

ENVIRONMENTAL CONDITIONS
Both temperature and humidity were controlled in this study. Air was supplied to the chambers at about 0.1-0.3 m³/min.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: water
Details on inhalation exposure:
Rats were exposed by inhalation to radioactive tracer particles and then randomly divided into experimental and control groups. One hour after a 20-min nose-only exposure to tracer particles, animals were placed in individual compartments in open-mesh stainless steel exposure cages. Cages were placed on one level only of a 1 m³ stainless steel chamber for a 4-h exposure to either purified or intentionally polluted air.

The tracer particles, tagged with tightly bound 51Cr, were monodisperse polystyrene latex (PSL) spheres having geometric diameters near 1.4 µm. Aerosols were produced from an aqueous suspension of 0.1% solids (by volume), using a Lovelace-type laboratory compressed-air nebulizer. The MMAD of the aerosol particles, as determined with a multistage laboratory impactor was about 1.6 µm.

Tracer particles were aerosolized, dried, brought to charge equilibrium, and passed into a nose-only exposure chamber. The individual tubes for holding rats in the device were made of perforated metal and were thin-walled to reduce thermal stress due to body heat.

The average amount of tracer material deposited per rat was less than 0.1 µCi, which is contained in less than 1 µg of particles. After the deposition of tracer particles was completed, the rats' noses were washed with water to remove radioactive particles. The animals were then placed in individual plastic counting tubes and inserted in a collimated counting apparatus. All rats that underwent deposition of PSL particles were counted twice for 100 s in this apparatus before they were placed in the pollutant exposure chambers. When the 4-h clean air or pollutant exposure was completed, the animals were periodically put into individual plastic counting tubes and the amount of radioactivity in the respiratory tract was determined at five additional predetermined times for up to 17 d. Fecal samples were collected from each rat 11 times during the first 48 h after tracer particle deposition. Coprophagy was minimized by the use of 1/2-inch mesh wire cage bottoms and by the frequent fecal collections.

Clearance curves were determined for each animal and half times obtained from least-squares fits for short- and long-term clearance data. Group mean values for pollutant-exposed and sham-exposed (control) groups were calculated. Half-times for experimental groups were subtracted from those for control groups and the differences tested for significance at the 90% level, using a two-tailed t-test.

Purified air supplied to the exposure chambers had been passed successively through a coarse particulate filter, a humidifier, a heater, and a high-efficiency particulate (HEPA) filter. Both temperature and humidity were controlled in this system. Air was supplied to the chambers at about 0.1-0.3 m³/min. Ammonia levels, due to the presence of rats, were measured as about 0.25 ppm or less under these conditions of exposure.

Stable, controllable salt aerosols with MMAD between 0.4 and 0.6 µm and sulfuric acid aerosols with MMAD of 1.0 µm, at mass concentrations up to 3 or 4 mg/m³ in air, were generated with compressed-air nebulizers loaded with aqueous sulfate solutions. A Collison-type three-jet nebulizer followed by a 85 Kr charge neutralizer and air-dilution drier, was used for ammonium sulfate and ferric sulfate particle generation. Under low humidity (30-40%) chamber conditions these aerosols were dry and were sized by electron microscopy. Ferric sulfate and ammonium sulfate aerosols were collected on electron microscope grids, using an electrostatic precipitator. The size distribution, count median diameter, mass median diameter, and geometric standard deviation were then determined by analysis of photographs. At high humidity (greater than 80%) the aerosols were wet and the multistage laboratory impactor was used.

Sulfuric acid aerosols were generated from solution by an all-glass compressed-air nebulizer. Sizing was performed by determining the titratable acidity.

Airborne mass concentrations were determined by putting two fiberglass filters in series inside the chamber and sampling at constant flow rates for up to 1 h. The first filter captured the aerosol and the second filter gave the change of filter weight due to humidity and allowed the efficiency of the primary sample filter to be verified.

Ozone, produced by passing medical grade oxygen through an electrical ozone generator, was introduced into a chamber run at constant flow rate and slight negative pressure. A Dasibi ultraviolet monitor was used to determine the ozone levels.

All samples for aerosol and gas characterization were acquired from the center of the breathing zone of the animals. Sampling lines were large-bore stainless steel for aerosol with Teflon for ozone.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Remarks on duration:
relative humidity: 39% (low-humidity exposure); 85% (high-humidity exposure)
Concentrations:
3.5 mg/m³; MMAD 0.4 µm
No. of animals per sex per dose:
10-12
Control animals:
yes
Statistics:
two-tailed t-test
Key result
Sex:
male
Dose descriptor:
LC0
Effect level:
3.5 mg/m³ air
Exp. duration:
4 h

Atmospheres

Concentrations and other characteristics of the atmospheres were remarkably stable from one exposure to another. Average data for all runs with standard deviations were: ozone, 0.79 ± 0.02 ppm; aerosol concentrations, 3.6 ± 0.4 mg/m³; low relative humidity, 39 ± 3%; high humidity, 85 ± 4%; MMAD of salt aerosols, 0.4 ± 0.1 µm ; and MMAD of sulfuric acid aerosols, 1.0 ± 0.2 µm. The aerosols had average estimated geometric standard deviations of 1.9 -2.3 from impactor data. Electron microscopy indicated geometric standard deviations of 1.6 -1.7.

Clearance Measurements

The low relative humidity sham-exposed animals were selected as primary controls to examine the effect of high relative humidity as a potential cotoxin. A total of 12 groups of 10-15 rats each were exposed to low-humidity clean air. The clearance data for these animals are given in Table 1 (see attached file). Some animals were excluded from the data analysis because they did not consume food or water at a sufficient rate to remove tracer particles from the gastrointestinal tract. When this occurred, in about 5% of the rats, clearance half-time values could not be obtained.

The effect of high humidity on clearance was interesting The short-term clearance half-time was longer in the high-humidity group by 0.9 h ; the long-term clearance half-time was diminished by high relative humidity by about 90 h (significant at p= 0.1).

As shown in Table 2 (see attached file), ozone alone at 0.8 ppm and low humidity statistically significantly slowed early clearance and accelerated late clearance. These effects were even greater at high humidity, the effects of humidity being roughly additive to those of ozone.

Ammonium sulfate at high or low humidity did not have any significant effects on early or late clearance compared to that in low-humidity clean-air controls.

The clearance data for aerosols combined with ozone are very similar to those for ozone alone. In no case is there a statistically significant difference between ozone alone and ozone with an aerosol at the same humidity. Further, in the majority of cases clearance patterns with sulfate particles and ozone both present lie between those for sham-exposed groups and groups exposed to ozone only. The atmosphere with the greatest effect on short-term clearance was sulfuric acid mist with ozone at high humidity.

Table 1: Clearance data for rats exposed to low-and high humidity clean air

      number of animals

    clearance half-time (h) a

 humidity  short-term  long-term  short-term  long-term
 low  124  123   11.17± 2.29  465 ± 328
 high  98 96    12.06± 2.31  376 ± 250
        0.89± 0.33  -89  ± 42

 a mean  ± SD

Table 2. Particle Clearance Responses of Rats Exposed for 4 h to Ozone and Sulfate Aerosols (3.5 mg/m3): Group Mean Differences from Low-Humidity Sham-exposed Animals 

 

Change in clearance half-time (h)a

Treatment

Short-term

Long-term

 

Low relative humidity

 

Sham

0 ± 0.3 (124)b

0 ± 42 (123)

0.8 ppm O3

0.9 ± 0.5c(39)

-152 ± 66c(40)

(NH4)2SO4d

0.1 ± 0.6 (29)

-14 ± 38 (29)

Fe2(SO4)3d

-0.3 ± 0.7 (28)

113 ± 53c(30)

H2SO4d

0.5 ± 0.7 (30)

79 ± 37c(30)

(NH4)2SO4+ 0.8 ppm O3

1.5 ± 0.6c(33)

-104 ± 53c(33)

Fe2(SO4)3+ 0.8 ppm O3

1.0 ± 0.6 (30)

-107 ± 95 (30)

H2SO4 ±0.8 ppm O3

0.7 ± 0.5 (40)

-208 ± 79c(40)

 

 

 

 

High relative humidity

 

Sham

0.9 ± 0.3c(98)

-89 ± 42c(96)

0.8 ppm O3

1.7 ± 0.8c(38)

-174 ± 85c(40)

(NH4)2SO4

0.6 ± 0.8 (29)

38 ± 80 (30)

Fe2(SO4)3

0.4 ± 0.8 (29)

-78 ± 79 (30)

H2SO4

1.3 ± 0.8 (29)

-69 ± 79 (30)

(NH4)2SO4+ 0.8 ppm O3

0.9 ± 0.7 (39)

-153 ± 107 (30)

Fe2(SO4)3+ 0.8 ppm O3

0.8 ± 0.9 (29)

-133 ± 92 (29)

H2SO4 ±0.8 ppm O3

2.6 ± 0.8c(40)

-158 ± 99 (27)

a   Mean ± SE. Positive values represent slowing and negative values acceleration of clearance.

b  Number of rats in each group is shown in parentheses.

c   Significantly different from low-humidity sham-exposed animals (p<0.1, two-tailedt-test).

d  Form inhaled is not usually the pure undissociated sulfate.

 

 

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: particle size distribution not given
Principles of method if other than guideline:
no data
GLP compliance:
not specified
Test type:
other: no data
Limit test:
no
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data
Route of administration:
inhalation: aerosol
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 test atmosphere concentrations:
yes
Duration of exposure:
8 h
Concentrations:
500-600, 600-700, 800-900 mg/m³
No. of animals per sex per dose:
6 -20
Control animals:
not specified
Mortality:
Mortality rates:
500-600 mg/m³: 0/6
600-700 mg/m³: 1/6
800-900 mg/m³: 8/20
The animals dying during exposure appeared to do so as a result of acute shock and airway constriction. Any sudden noise or other disturbance was likely to precipitate such an event. After exposure, the survivors recovered without any noticable effect.

0/6, 1/6, and 8/20 animals exposed to an aerosol of the test substance at concentrations of 500 -600, 600 -700, and

800 -900 mg/m³, respectively, died.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
according to guideline
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
Deviations:
yes
Remarks:
open application
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
male and female Wistar rats
- Age at study initiation: 5-6 weeks
- Housing: individually housed in stainless-steel cages
- Acclimation period: at least 5 days
no further data

ENVIRONMENTAL CONDITIONS: no data
Type of coverage:
open
Vehicle:
other: water-acetone solution (no further detail reported)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
Hair was first removed from an area of 3 x 4 cm² on the back of rats with an electric hair clipper, and then the chemical substances dissolved in acetone and water were applied in a single dose to the skin surface of the clipped backs of the animals. The application sites were not covered but the treated areas were prevented from being licked by using a plastic collar or by fixing the animals on a plastic plate.

REMOVAL OF TEST SUBSTANCE: no data
Duration of exposure:
no data
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical and behavioural abnormalities, body weight, mortality, gross lesions
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw

Based on the results of this test, the LD50 was >2000 mg/kg bw.

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
OECD TG 434

Additional information

ANIMAL STUDIES

 

Oral

In an acute oral toxicity study, a 30% aqueous solution of the test substance was administered by gavage. Groups of 10 rats/sex received doses of 6400, 5000, 4000, 3200, and 2500 mg/kg bw and were observed for 7 days.

Mortality was 18/20, 101/20, 9/20, 4/20, and 0/20 in the groups given 6400, 5000, 4000, 3200, and 2500 mg/kg bw, respectively. All deaths occurred within 48 hours after dosing. Clinical signs of toxicity were observed in all but the lowest dose group and comprised staggering, abdominal/lateral/dorsal position, apathy, laboured/irregular breathing, secretion out of the eyes and mouth, redness of the eyes and nose. All surviving animals were normal by day 2 post dose. At necropsy, fluid in the thoracic cavity was observed in a few animals. In three animals, the stomach was filled with liquid, and bloody mouth and forelegs were noted. No pathological findings were noted with regard to the inner organs.

The LD50 was 4250 (3788 - 4769) mg/kg bw. No clinical signs were noted at doses up to and including 2500 mg/kg bw (BASF, 1969).

In another study similar to OECD TG 423, LD50 values of about 2000 mg/kg bw are reported for rats and of > 2000 mg/kg bw in mice (Yamanaka et al., 1990). Observations and examinations included clinical and behavioural abnormalities, body weight, mortality, and gross lesions. All animals were subjected to necropsy. In a full LD50 test according to the Toxicity Guidelines of Japan (1984) an oral LD50 for mice of 3040 mg/kg bw was obtained. Details on clinical signs and necropsy findings were not given (Yamanaka et al., 1990).

 

Dermal

Three male and 3 female Wistar rats were administered the test substance at a dose level of 2000 mg/kg bw and were observed for 14 days. Observations and examinations included clinical and behavioural abnormalities, body weight, mortality, and gross lesions. All animals were subjected to necropsy. Based on the results of this test, the LD50 was >2000 mg/kg bw. Details on clinical signs and necropsy findings were not given (Yamanaka et al.,1990). In the same study, three male and 3 female ddY mice were administered the test substance at a dose level of 2000 mg/kg bw and were observed for 14 days. Here, also LD50 values of > 2000 mg/kg bw are reported after dermal application of ammonium sulfate. Details on clinical signs and necropsy findings were not given.

 

Inhalation (see also section 7.9.3)

20 guinea pigs were exposed for 8 hours to an aerosol of the test substance at concentrations of 500 -600, 600 -700, and 800 -900 mg/m³, respectively. The animals were observed for mortality and signs of gross toxicity. 0/6, 1/6, and 8/20 animals exposed to the low, mid, and high concentration, respectively, died. The animals dying during exposure appeared to do so as a result of acute shock and airway constriction. Any sudden noise or other disturbance was likely to precipitate such an event. After exposure, the survivors recovered without any noticable effect.

The acute inhalation toxicity of ammonium sulfate aerosols (average diameter 1 - 3 µm) is very low with 8 -h LC50 values of greater than 900 mg/m³ for guinea pigs. Rats were exposed repeatedly for 8 h/d to 1000 - 1200 mg/m³ (average diameter 2 - 3 µm) without mortality. No specific signs of toxicity were reported from these studies (Pepelko et al., 1980).

Mucociliary clearance was neither significantly affected in male rabbits that were exposed to 2 mg/m³ for one hour (mass median diameter: 0.4 µm) (Schlesinger, 1984), nor in sheep that were exposed to 1.1 mg/m³ (< 1 µm) for 20 minutes (Sackner et al., 1981) nor in rats exposed to 3.6 mg/m³ (0.4 µm) for 4 h (Phalen et al., 1980).

Guinea pigs were exposed for 1 hour to aerosols of the test substance at concentrations of 0.13, 0.20 0.30, and 0.81 mg/m³. The mass median diameter (MMD) was 0.1 - 0.8 µm. A slight increase in pulmonary flow resistance and a statistically significant decrease in pulmonary compliance was observed at all concentrations and particle sizes tested. Pulmonary resistance was slightly increased and compliance was statistically significantly decreased in guinea pigs exposed to 0.5 - 9.5 mg/m³ for one hour (Amdur et al., 1978). Pulmonary mechanics were not altered in dogs breathing ammonium sulfate aerosol at a concentration of 4.1 mg/m³ for 4 h (Sackner et al., 1981).

 

 

HUMAN STUDIES (see also section 7.10.5)

 

Oral

A case of a fatal poisoning with ammonium sulfate was reported from an 85-year-old woman after drinking an unspecified amount of ammonium sulfate dissolved in beer in a suicidal attempt. Heart, lung, liver and kidney did not show any pathological findings on macro- and microscopical examination. There was mild petechial hemorrhage in the gastric fundic mucosa without any erosion or corrosion. In serum, ammonium and sulfate ions were significantly increased (25 000 µg/dl and 12.35 mEq/l, resp.; normal range 30 - 80 µg/dl and 0.25 - 0.35 mEq/l, resp.) (Sato et al., 1999).

 

Inhalation

Exposure of 13 healthy male volunteers to ammonium sulfate aerosol for four hours at a concentration of 0.133 mg/m³ (MMAD 0.55 µm) produced no significant effects related to 19 measured pulmonary parameters, including specific airway resistance, forced vital capacity, and forced expiratory flow (Stacy et al., 1983).

No significant changes in pulmonary parameters were reported from healthy and asthmatic volunteers exposed for 2 hours to ammonium sulfate (0.1 - 0.3 mg/m³; MMAD 0.3 - 0.6 µm) (Avol et al., 1979).

At 1 mg sulfate/m³ (MMAD 1 μm) ammonium sulfate inhaled for 16 minutes produced a small but significant decrease in expiratory flow in healthy subjects. Carbachol induced bronchoconstriction was slightly enhanced (no statistical evaluation) (Utell et al., 1982).

Pulmonary function (measured by body plethysmography and spirometry), and bronchial reactivity to metacholine were not affected in 20 non-smoking volunteers after a 4-hour exposure to 0.5 mg/m³ ammonium sulfate. The exposures included two 15-minute light to moderate exercise stints per day in the exposure chamber (Kulle et al., 1984).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The LD50 was greater than 2000 mg/kg bw. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation (EU) No 2016/1179.

On the basis of the available animal and human data on acute toxicity following inhalation, there is no need for classification.