Ammonium carbamate

Endpoint summary

Additional information

When ammonium carbonate, ammonium hydrogencarbonate, ammonium carbamate, or ammonium chloride with sodium carbonate dissolves in water, several equilibrium reactions establish (Wen, N. & Brooker, J. Phys. Chem. 1995, 99, 259-268):

NH₄⁺(aq) + H₂O(l)↔NH₃(aq) + H₃O⁺(aq)

CO₃^2-(aq) + H₂O(aq) ↔ HCO₃^-(aq) + OH^-(aq)

CO₃^2-(aq) + NH₄⁺(aq) ↔ HCO₃^-(aq) + NH₃(aq)

HCO₃^-(aq) + NH₃(aq) ↔ H₂NCOO^-(aq) + H₂O(l)

H₂NCOO^-(aq) + H₂O(l) ↔ CO₃^2-(aq) + NH₄⁺(aq)

The overall equilibrium among the carbonate, bicarbonate, carbamate, ammonium and free ammonia can be expressed as:

H₂NCOO^-(aq) + H₂O(l) ↔ CO₃^2-(aq) + NH₄⁺(aq) ↔ HCO₃^-(aq) + NH₃(aq)

It was shown that aqueous solutions of ammonium carbonate, ammonium bicarbonate and ammonium carbamate give very similar Raman spectra. It was confirmed that the solutions contain common species such as CO₃^2-(aq), HCO₃^-(aq), H₂NCOO^-(aq), NH₄⁺(aq) and solvent H₂O(l). Furthermore,¹³C-NMR studies conducted with these solutions provided complementary evidence for the same equilibrium (Wen & Brooker, 1995).
Furthermore, a number of publications describe a shift of the equilibrium depending on the pH of the solution:
Even at weakly acidic conditions (acetic acid/acetate) a complete decomposition of ammonium carbamate into ammonia and carbon dioxide occurs in less than a second (Faurholt, C., Dan. Vidensk. Selsk., Mat.-Fys.Medd. 3 (1921) 20; Roughton, F. J. W., J. Amer. Chem. Soc. 63, 1941, 2930-2934). Gradual decomposition of carbamate to bicarbonate/carbonate with decreasing pH (≤9.93) has also been shown by Mani et al. (Green Chemistry, 2006, 8, 995-1000)..

A rate constant for decomposition of carbamate at pH 9.05 is reported to be 0.038 sec^-1at 0 °C and 0.22 sec^-1at 25 °C (Blakeley et al., 1969; Roughton, 1941), which corresponds to half-lives of about 20 and 3 seconds, respectively.
These results are also confirmed by the analysis of¹³C{¹H}-NMR spectra obtained dissolving ammonium carbamate in D₂O, in which signals referred to the ions carbamate and bicarbonate/carbonate have been observed (BASF SE, analytics report, order number 14Y00397, 2014). The data show that a 1:1 equilibrium between ammonium carbamate and bicarbonate/carbonate establishes after approximately 2 hours without further concentration shifts after that point.
In a follow-up experiment,¹³C{¹H}-NMRof a 10% solution of ammonium carbamate in D₂O (pH 9-9.5) were recorded (BASF SE, analytics report, order number 14E00249). Two signals at 166.6 ppm (ammonium carbamate) and 163 ppm (ammonium hydrogencarbonate), respectively, were detected after 32 scans (2:16 minutes), the ratio being 1:0.4. After >12 hours, a ratio of 1:1.5 had established. The experiment was repeated with a 1% solution of ammonium carbamate in D₂O (pH 9-9.5), which was also the lowest concentration at which NMR signals could be obtained that were distinctive enough for interpretation. Here, the ammonium hydrogencarbonate signal was the only detected signal after 10 minutes, indicating complete decomposition of the carbamate anion.
The results above indicate that the hydrolysis rate of ammonium carbamate increases with decreasing concentrations. Physiological concentrations can be anticipated to be much lower than the concentrations tested above, and thus it can be expected that decomposition will take place even faster under physiological conditions.

The instability of ammonium carbamate under acidic conditions has also been demonstrated by¹³C{¹H}-NMR. After recording a spectrum of a 10% solution of ammonium carbamate in D₂O, the solution was acidified with 20% DCl and another spectrum was recorded (pH 1). As expected, no¹³C signals were detected after acidification as ammonium carbamate and ammonium hydrogencarbonate had completely decomposed.

The pH of lung-lining fluid in humans is approx. 6.6 (Bodem et al., Am Rev Respir Dis., 1983 Jan; 127(1):39-41), that of human skin usually below 5 (Lambers et al., In J Cosmet Sci., 2006 Oct;28(5):359-70), and that of gastric acid in the stomach 1-2. Based on the literature data in combination with¹³C{¹H}-NMR spectra, it can be anticipated that decomposition of ammonium carbamate into its hydrolysis products takes place upon inhalative, dermal or oral uptake of the substance, because the equilibrium will be shifted towards the right side. Thus, the systemic toxicological effects of ammonium carbamate can be predicted from its dissociation products. As a result, a read-across approach using data from ammonium ions or ammonia, as well as bicarbonate or carbonate ions, is considered applicable to cover those endpoints where no data for ammonium carbamate is available. This strategy is in accordance with section 1.5 of Annex XI of the REACH Regulation.

The systemic fates of ammonium/ammonia and carbonate/bicarbonate are described in the following:
At physiological pH in aqueous media, the ammonium ion is in equilibrium with un-ionised ammonia. An ammonium ion via the equilibrium with ammonia is readily taken up. Some evidence exists also for an active transport of the ammonium ion from the intestinal tract. It has been shown that ammonia transport by the human colon still occurred when the luminal pH was reduced to 5, where non-ionised ammonia would be virtually absent (WHO, 1986). Non-ionised ammonia (NH₃) passes tissue barriers with ease. Once absorbed, ammonium is transported to the liver where it is metabolised to urea and excreted via the kidneys. Minor amounts of nitrogen are incorporated in the physiological N-pool (WHO, 1986). The ammonium ion serves a major role in the maintenance of the acid-base balance. In the normal pH range of blood, the NH₄⁺/ NH₃is about 100 (WHO, 1986).

Carbonate is a normal intermediate in the metabolism of endogenous carbon compounds. Physiologically, it plays an integral role in the extracellular buffering system of blood and the interstitial fluid of vertebrates as seen in the following equation:

 H₂O + CO₂<=> H₂CO₃<=> H⁺+ HCO₃^-

At low systemic pH, the concentration of hydrogen ions is high. As a consequence, the equilibrium of the equation is shifted to the left; hence as a compensatory response CO₂is exhaled (hyperventilation). When on the other hand pH is high, the concentration of hydrogen ions in the blood is low, so the kidneys excrete bicarbonate (HCO₃⁻). This causes the equation to shift to the right, essentially increasing the concentration of hydrogen ions, causing a more acidic pH.