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Ammonium bicarbonate rapidly dissociates in biological fluids to yield ammonium ion (NH4+) and bicarbonate ion (HCO3-). Ammonium ion then reaches equilibrium with ammonia (NH3) in a pH-dependent fashion and both are integral components of normal metabolic processes and play an essential role in the physiology of man and other species. Bicarbonate ion reaches equilibrium with CO2 and H2O in aqueous solution and this equilibrium reaction acts as the major extracellular buffer system in blood and interstitial fluids of vertebrates.

Discussion on bioaccumulation potential result:

Ammonium bicarbonate rapidly dissociates in biological fluids to yield ammonium ion (NH4+) and bicarbonate ion (HCO3-). Ammonium ion then reaches equilibrium with ammonia (NH3) in a pH-dependent fashion and both are integral components of normal metabolic processes and play an essential role in the physiology of man and other species. Bicarbonate ion reaches equilibrium with CO2and H2O in aqueous solution and this equilibrium reaction acts as the major extracellular buffer system in blood and interstitial fluids of vertebrates.

Some studies on the metabolism of ammonium hydrogencarbonate were available:

In a study with 12 Wistar rats, the absorption of ammonia from the small and large intestine of rats and the effects of hydrogen and bicarbonate ions and hypertonicity on this absorption were studied (Swales, 1970). Animals received four consecutive intestinal infusions of 3 ml solutions containing 70 mEq ammonium hydrogencarbonate through a cannula. Ammonia was readily absorbed by the rat intestine, while the net bicarbonate absorption was increased and net bicarbonate secretion was decreased in the presence of ammonia.

It is known, that ammonium is produced primarily from the amino acid glutamine, which is delivered to the kidney via the circulation and taken up by the proximal tubule (Good, 1990).

The link between the renal excretion of ammonium bicarbonate and glutamine metabolism was evaluated in a study, where female Wistar rats received either intraperitoneal injections of 2.5 mmol/kg bw or an intravenous injection of 0.3 M/kg bw ammonium hydrogencarbonate (Vinay, 1978). The single intraperitoneal injection resulted in a 29 % decrease in the tissue concentration of 2-oxoglutarate and a slight increase in the tissue concentration of glutamine in freeze-clamped kidneys. The constant infusion over 60 minutes at a rate of 15 μM/min (approx. 1.2 mg/min) produced a similar result with a significant increase in tissue glutamine content and renal vein glutamine concentration. Also, the arterial concentration of ammonia rose markedly and renal ammonia production was acutely depressed. Ammonia was then extracted from the renal circulation, but not all this ammonia is recovered in the urine. Simultaneously net glutamine extraction is converted to net glutamine production.

The protective effect on renal function from the damage of bilateral renal artery occlusion was analyzed in male Sprague-Dawley rats receiving 0.28 M ammonium hydrogencarbonate or sodium hydrogen carbonate in drinking water (Atkins, 1986). The ammonium bicarbonate loaded animals had significantly higher urine flow rates than controls, while the sodium hydrogencarbonate treated animals did not.

The intake of ammonium hydrogencarbonate for 4 days led to an increase in urine urea and urine ammonium content in man (Fine, 1977).

When awake dogs received an intravenous 0.36 mmol/kg bw/h ammonium hydrogencarbonate for 4 h, all essential amino acids were sharply reduced in plasma while tryptophan in cerebrospinal fluid was unchanged (Jeppsson, 1980).

This influence of ammonium hydrogencarbonate intake on the glutamine synthesis was confirmed in sheep, when infusion of 23.4 μmol/kg bw ammonium hydrogencarbonate was given for 4 days at a rate of 60 g/h (Nieto, 2002).

 

In addition, studies with sodium bicarbonate could be taken into account for assessment since its dissociation led to free bicarbonate ion (HCO3-) as ammonium hydrogencarbonate. In one study it was shown that one hour after intraperitoneal injection of sodium bicarbonate to mice, more than 90 % of the total radioactivity injected was lost through the lungs (Skipper, 1949). In another study, rats were killed 30 min after 5 intraperitoneal injections of sodium bicarbonate. The urine contained 1.3 % of the radioactivity, and more than 50 % was exhaled as respiratory carbon dioxide (Solomon, 1941).

 

Together the data suggest, that the toxicological profile of ammonium hydrogencarbonate depends more on the single ions ammonia and bicarbonate. Since both are part of the normal metabolic processes and the physiology of man, a possible excess intake would be regulated mostly by excretion via urine.