Absorption, Distribution and Excretion
In aqueous environments, such as the human body, ammonium sulfate completely dissociates into ammonium ions (NH₄⁺) and sulfate ions (SO₄²⁻). In aqueous solutions at physiological pH, ammonium ions are in equilibrium with unionized ammonia…ammonium ions play a crucial role in maintaining acid-base balance. Within the normal pH range of blood, the NH₄⁺/NH₃ ratio is approximately 100. Ammonium ions are readily absorbed through equilibrium with ammonia. There is also some evidence that ammonium ions can be actively transported from the intestines. Studies have shown that even when the intestinal pH drops to 5 and unionized ammonia is almost nonexistent, the human colon can still transport ammonia. Absorbed ammonium is transported to the liver and metabolized into urea, which is then excreted via the kidneys. A small amount of nitrogen enters the physiological nitrogen pool. Sulfate absorption depends on the intake. After volunteers orally ingested magnesium sulfate or sodium sulfate (5.4 g sulfate), 30%–44% of sulfate was excreted in urine within 24 hours. When the sulfate dose exceeds intestinal absorption, sulfate is excreted in feces. Sulfates in the intestines may bind with water in the intestinal lumen, potentially causing diarrhea in high doses. Sulfates are a normal component of human blood and do not accumulate in tissues. The kidneys regulate sulfate levels through reabsorption mechanisms. Sulfates are normally excreted through the kidneys. Ammonium sulfate also plays an important role in the detoxification of various endogenous and exogenous compounds because it can bind with these compounds to form soluble sulfate esters, which are ultimately excreted in urine. In studies of rabbits, hamsters, and guinea pigs,
sup>35
S-labeled ammonium sulfate aerosols with particle sizes of 0.3 and 0.6 micrometers (MMAD) have been shown to reach the lungs. However, a significant portion of the compound remains in the nasal cavity. Clearance via the lungs (through the blood and urinary system) takes 18 to 20 minutes. 95% of sulfate collected by the urinary system is excreted within 6 hours. Clearance studies indicate no significant differences between species. Ammonium sulfate does not inhibit the induction of pulmonary aryl hydroxylase (an enzyme involved in the metabolism of benzo[a]pyrene and other carcinogens) (other air pollutants have been reported to cause this effect).

Toxicity Summary
Identification and Uses: Ammonium sulfate is a white solid. It is primarily used as a nitrogen source in commercial fertilizer mixtures or as a direct fertilizer application, accounting for over 90% of its total usage. It is also used for various industrial purposes and is approved by the EU as a direct food additive. It is registered for use in the US, but its approved pesticide uses may change periodically, so it is essential to consult federal, state, and local authorities for current approved uses. Ammonium sulfate is also found in non-agricultural products intended for public use (e.g., cleaning products, paints); its content can reach up to 50%. Ammonium sulfate has been shown to be used as a breaker in hydraulic fracturing. Human Exposure and Toxicity: In humans, inhalation of ammonium sulfate aerosol at concentrations of 0.1 to 0.5 mg/m³ for 2 to 4 hours did not produce pulmonary effects. In healthy volunteers, acute exposure to ammonium sulfate at a concentration of 1 mg/m³ resulted in only mild pulmonary effects, manifested as decreased expiratory flow, pulmonary airflow resistance, and dynamic lung compliance. Eighteen individuals who drank water contaminated with ammonium sulfate fertilizer (1500-2000 mg/L) experienced gastrointestinal pain similar to acute enteritis. All symptoms resolved within 24 hours. Ammonium sulfate did not induce chromosomal aberrations in mammalian or human cell cultures. Ammonium is also an endogenous substance, playing an important role in maintaining acid-base balance. Small amounts of ammonium nitrogen are incorporated into the physiological nitrogen pool. Sulfate is a normal intermediate in the metabolism of endogenous sulfur compounds, excreted in its original or conjugated form in urine. Animal studies: Ammonium sulfate exhibits relatively low acute toxicity (oral LD50 in rats: 2000-4250 mg/kg body weight; dermal LD50 in rats/mouse > 2000 mg/kg body weight; 8-hour inhalation LC50 in rats > 1000 mg/m³). Following oral administration, at doses close to or exceeding the LD50, immediate clinical symptoms appeared, including unsteady gait, weakness, lethargy, and dyspnea and irregular breathing. Pure ammonium sulfate is non-irritating to the skin and eyes of rabbits. A 14-day rat inhalation study (testing only at a dose of 300 mg/m³) found no histopathological changes in the lower respiratory tract. After 13 weeks of feeding rats with ammonium sulfate, only males in the high-dose group developed diarrhea. Three rabbits were administered a total dose of 1500 mg/kg of ammonium sulfate, and all rabbits developed similar symptoms, such as dilated pupils, irregular respiratory rhythms, localized and generalized convulsions, leading to respiratory failure and cardiac arrest. Electroencephalography (EEG) showed slow waves, inhibitory waves, and high-amplitude slow wave patterns, which are commonly clinically manifested in hyperammonemia in humans and animals. Serum ammonium and inorganic sulfate ion concentrations were significantly elevated, and blood gas analysis showed severe metabolic acidosis. These results, primarily from EEG, indicate that a rapid increase in blood ammonium ions can damage the central nervous system without microscopic observation. Ammonium sulfate is not mutagenic to bacteria (Ames test) or yeasts with or without metabolic activation systems. It also does not induce chromosomal aberrations in mammalian or human cell cultures. Similar to other salts, high doses of ammonium sulfate may promote the growth of gastric tumors in rats. However, under the same testing conditions, ammonium sulfate is far less toxic than sodium chloride. In a 13-week ammonium sulfate-fed rat study, no histological changes were observed in the testes at doses up to 1792 mg/kg body weight. Ovaries were not examined. Ecotoxicity studies: The most susceptible amphibian was 6-week-old Pseudacris regilla tadpoles. Acute marine toxicity data are available for fish, invertebrates, and phytoplankton, with phytoplankton being the most susceptible. Growth inhibition was observed at concentrations of 0.7 mg/L and above for Gymnodinium splendens and Gonyaulax polyedra. For marine invertebrates, Perna viridis showed the lowest toxicity (96-hour LC50 = 47.7 mg/L). For marine fish, the effect size was lowest in juvenile Sciaenops ocellatus, with an LC50 (10 days) of 27 mg/L.

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Interactions
We tested the effects of several inhaled gases on the respiratory defense system of rats. The substances studied included ozone as well as aerosols of ammonium sulfate, ferric sulfate, and sulfuric acid; relative humidity was also a controlled experimental variable. Each sulfate was studied individually as a submicron aerosol at a concentration of 3.5 mg/m³, mixed with ozone at a concentration of 0.8 ppm. Results were compared with those of sham-exposed animals and rats exposed to ozone alone. Exposure to air pollutants was conducted in a stainless steel chamber, once, for 4 hours. The endpoint for assessing the effect was the measurement of early and late clearance rates of radiolabeled insoluble tracer particles. Tracer particles were inhaled before exposure to air pollutants, and particle clearance was tracked for approximately two weeks. Ozone alone slowed early (0–50 hours post-exposure) particle clearance and promoted late (2–17 days) clearance. High humidity typically amplifies these effects of ozone and many other atmospheric components studied. The effects of sulfate aerosols alone on early or late clearance are relatively small. The combined effects of ozone and aerosols are similar to those of ozone alone. The data do not support the hypothesis that sulfate aerosols and ozone synergistically alter respiratory clearance; sulfuric acid may be an exception. These data alone cannot predict the overall health effects of the substances studied. The effects of inhaled ammonium sulfate on the carcinogenicity of benzo[a]pyrene in the lungs of Syrian golden hamsters were investigated. During the first 6 months of the study, exposure to airborne ammonium sulfate at concentrations 20 times the US average ambient concentration resulted in a significant reduction in the carcinogenicity of benzo[a]pyrene (p<0.05). However, at the end of the study (2 years), there was no difference in cancer incidence between the two groups receiving benzo[a]pyrene and those receiving benzo[a]pyrene plus ammonium sulfate. Furthermore, at the concentrations studied, inhaled ammonium sulfate did not significantly increase the incidence or severity of pneumonia or pulmonary fibrosis in the hamsters. However, while inhaling ammonium sulfate did increase the incidence of emphysema, it did not increase its severity. In the first 6 months of the study, the incidence of cancer was reduced in animals simultaneously exposed to benzo[a]pyrene and ammonium sulfate, suggesting an interaction between sulfate and benzo[a]pyrene, but one insufficient to provide long-term cancer protection. Inhalation of sulfate did not enhance the carcinogenic effects of benzo[a]pyrene. In controlled exposure experiments on rats, a previously unexpected synergistic effect was observed between oxidizing air pollutants ozone or nitrogen dioxide and inhalable ammonium sulfate aerosols. The response of rat lungs to these pollutants was quantified by measuring the apparent rate of collagen synthesis in the lung tissue of exposed animals in vitro. The dose-response curves for both O₃ and NO₂ were altered in the presence of 5 mg/m³ (NH₄)₂SO₄ aerosols. Morphological and histological observations of the lungs of rats exposed to high concentrations of ozone (with or without simultaneous exposure to (NH₄)₂SO₄ particles) confirmed this synergistic effect. In another set of experiments, rats were exposed to a mixture of ozone and sulfuric acid aerosols (submicron-sized aerosols) at near-ambient concentrations. These experiments also observed an enhancing effect of ozone on the rate of pulmonary collagen synthesis. These observations may have broad implications for the appropriate assessment of laboratory data in the development of ambient air quality standards and/or occupational safety thresholds. It has been reported that continuous exposure of rats to ammonium sulfate (5 mg/m³) and ozone (0.2 ppm) for 7 days resulted in a synergistic effect on the rat lungs. More (complete) data on interactions of ammonium sulfate (7 types in total) can be found on the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 3000 mg/kg
Oral LD50 in rats: 4250 mg/kg body weight (95% confidence interval: 3788 - 4769 mg/kg body weight)
Dermal LD50 in rats: > 2000 mg/kg body weight
Oral LD50 in mice: 3040 mg/kg body weight
For more non-human toxicity values (complete) and data on ammonium sulfate (8 in total), please visit the HSDB records page.

[1]. DIXON M. A nomogram for ammonium sulphate solutions. Biochem J. 1953 Jun;54(3):457-8.

Ammonium sulfate is a white, odorless solid that readily settles in water but is soluble in water. (US Coast Guard, 1999)
Ammonium sulfate is an inorganic sulfate produced by reacting sulfuric acid with two equivalents of ammonia. It is a white solid with a high melting point (decomposes above 280°C), extremely soluble in water (70.6 g/100 g water at 0°C; 103.8 g/100 g water at 100°C), and is widely used as a fertilizer for alkaline soils. It is both an ammonium salt and an inorganic sulfate.
Ammonium sulfate (Mascagnite) is a mineral with the chemical formula (N3-H4)2S6+O4 or (NH4)2(SO4). Its symbol in the International Mineralogical Association (IMA) is MSc.
Diammonium sulfate. It is used for the chemical separation of proteins.
See also: ...See more...

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Therapeutic Uses
Ammonium sulfate is a non-central nervous system depressant anesthetic that has been reported to have analgesic effects that can last for days to weeks, and has had few reported side effects in adult studies.

H8N2O4S

132.14

132.02

7783-20-2

Ammonium sulphate,≥99.0%,AR-15N2;43086-58-4;Ammonium sulphate-d8;13814-01-2

6097028

White or brown orthorhombic crystals
Orthorhombic crystals or white granules
Brownish gray to white crystals according to degree of purity

1.76

330ºC at 760 mmHg

280ºC

26 °C

n20/D 1.396

0.751

2

4

0

7

62.2

0

S(=O)(=O)([O-])[O-].[N+]([H])([H])([H])[H].[N+]([H])([H])([H])[H]

BFNBIHQBYMNNAN-UHFFFAOYSA-N

InChI=1S/2H3N.H2O4S/c;;1-5(2,3)4/h2*1H3;(H2,1,2,3,4)

diazanium;sulfate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: 100 mg/mL (756.77 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)