Reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
The reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate is readily absorbed, distributed, metabolised and excreted following oral and inhalation exposure.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The reaction mass consists of sodium sulphate, potassium sulfate, and ammonium sulphate. All three substances dissociate in an aqueous environment, such as the body, completely into the corresponding ions sodium (Na⁺), ammonium (NH₄⁺), potassium (K⁺), and sulphate (SO₄^2-), respectively.

 

Sodium is essential for the maintenance of the total body fluid homeostasis and the blood pressure. It is also a key ion for the osmotic balance between the intra- and extracellular fluid, resulting in the electrochemical gradient, amongst others, essential for neuronal function. Due to these roles, the body sodium level is regulated by hormones and ion-pumps on the cellular level. The absorption of sodium is very fast and almost complete, while its elimination is very low since it is reabsorbed in the glomeruli of the kidney. Nonetheless, the main elimination route for sodium is via urine.

 

Like sodium, potassium is also a key element in regulation of osmotic balance between cells and the interstitial fluid as well as in neuronal function. The cellular content is regulated by ion pumps, which pump 3 sodium ions out of the cell and 2 potassium ions into the cell, thus creating an electrochemical gradient over the cell membrane.

While sodium makes up most of the cations of blood plasma (extracellular) at a reference range of about 145 milliequivalents per litre (3.3 grams), potassium makes up the major intracellular cations at about 150 milliequivalents per litre (4.8 grams) (Potts, 1964).

The absorption of potassium is achieved by active transport and is fast and almost complete. The excretion occurs mainly via the kidney and only partly by faeces.

 

Ammonium ions are predominantly produced from the catabolism of amino acids in virtually all cells. At physiological pH in aqueous media, the ammonium ion is in equilibrium with un-ionized ammonia, according to the following equation: NH₄⁺+ H₂O <--> NH₃+ H₃O⁺.

The ammonium ion serves a major role in the maintenance of the acid-base balance. In the normal pH range of blood, the NH4+/NH3 ratio is about 100 (WHO, 1986).

The uptake of an ammonium ion occurs readily via the equilibrium with ammonia, although some evidence exists also for an active transport of the ammonium ion from the gastro-intestinal tract (WHO, 1986).

Absorbed ammonium is transported to the liver and metabolized to urea and excreted via the kidneys, while minor amounts of nitrogen are incorporated in the physiological N-pool (WHO, 1986).

 

Sulphate is a constituent of the blood and as well as a metabolite of sulphur-containing amino acids. The absorption of sulphate depends on the amount ingested. Absorption of small amounts of sulphate from the gastro-intestinal tract occurs rapidly and almost completely. Regarding excretion it was found, that 30 - 44% of sulphate was excreted in the 24-hour urine of volunteers after oral administration of magnesium or sodium sulphate (5.4 g sulphate). At high doses that exceed the intestinal absorption potential, sulphate is excreted in faeces with possible cathartic effects. After absorption, the free sulphate ions are rapidly distributed over the extracellular space, with the apparent distribution volume being ~ 20% of the body volume. The serum concentration of sulphate in humans ranges between 1.4 and 4.8 mg/100 mL, with a mean of about 3.1 mg/100 mL (Cocchetto and Levi, 1981). The sulphate levels are regulated by the kidney through a resorption mechanism, so that excess sulphate originated from the amino acid metabolisms is usually eliminated by renal excretion. The daily sulphate excretion is reported to be 0.20 to 0.25 mmol/kg bw/day and being higher in children (Health Canada, 1987 and 1994).

 

Based on the absorption, metabolism and excretion properties as well as the available toxicological data of all three constituents of the reaction mass, it can be concluded, that ammonium sulphate is the most critical substance within the reaction mass. Thus, available data on ammonium sulphate will be used for hazard assessment of the toxicological properties of the reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate.

References

Potts, W.T.W.; Parry, G. (1964). Osmotic and ionic regulation in animals. Pergamon Press.

Canada Health, November 1987 (updated September 1994), Sulfate.Avaulable: http://www.hc-sc.gc.ca

Cocchetto, D.M. and Levy, G. (1981). Absorption of orally administered sodium sulphate in

humans. J. Pharm. Sci. 70(3):331-333.

WHO (1986). Environmental Health Criteria 54. Ammonia. Published under the joint sponsorship

of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization., 1986.

Discussion on bioaccumulation potential result:

Besides the oral intake, ammonium sulphate can be absorbed via the inhalation route as shown in a study with rabbits, hamster and guinea pigs (Godleski and Leighton, 1978). In this study it was demonstrated that S35-labelled ammonium sulphate aerosols with a MMAD of 0.3 and 0.6 µm are able to reach the lung, however, a substantial proportion of the compound was retained in the nose and subsequently swallowed. The half-life for clearance from the lung (via the blood and urinary tract) was determined to be 18 to 20 minutes.

 

When three anesthetized Japanese White rabbits were administered a single dose of 1500 mg/kg bw ammonium sulphate by gastric intubation, animals exhibited mydriasis and slight irregular respiratory rhythms 10 to 20 min after ingestion (Sato, 1999). After further depression of respiration rate, the animals finally died within 70 min after dosing due to cardiac arrest. The analysis of the blood showed that both the ammonium and sulphate concentration in serum dramatically increased. In addition a severe metabolic acidosis developed after ingestion of ammonium sulphate, e. g. decrease in pH, HCO3- and base excess.