Ammonium chloride

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Ammonium chloride is an inorganic fine crystalline homogenous powder (at 20°C). It has a molecular weight of 53.491 g/mol and is very soluble in water (> 10000 mg/L at 20°C) (see section 4.8: water solubility).

 

Absorption 

In an acute (gavage) study with rats, ammonium chloride caused mortality in both sexes. An LD50 of 1410 mg/kg bw was established based on observed mortality. Clinical signs of toxicity included dyspnoea, apathy, abnormal position, staggering, twitching, atony, tonic convulsions, poor general state and exophthalmia (BASF AG, 1983). The expression of systemic toxicity in rats after oral exposure allows the conjecture that systemic exposure to Ammonium Chloride occurs after absorption in the gastrointestinal tract.

 

No experimental data are available assessing the the dermal and inhalative absorption of ammonium chloride. However, in view of its low molecular mass (less than 200 g/mol), its very high water solubility, and the fact that systemic exposure occurs via the gastrointestinal tract, it is very likely that absorption of ammonium chloride will occur if inhaled (Guidance on information requirements and chemical safety assessment R7c). Based on the particle size distribution analysis, ammonium chloride will potentially be deposited in the upper respiratory tract as ca. 37% of ammonium chloride particles have an aerodynamic diameter < 100 µm while particles with aerodynamic diameters less than 10 µm and/or 4 µm, respectively are absent (see Chapter particle size distribution). Hence, potential absorption is expected to be restricted to the upper respiratory tract.

Based on its physiochemical properties, dermal absorption of ammonium chloride is expected to be low. With its water solubility higher than 10000 mg/L, ammonium chloride may be too hydrophilic to cross the lipid rich environment of the stratum corneum (Guidance on information requirements and chemical safety assessment R7c).

 

Distribution

In vivo, ammonium chloride is present in its ionized form, viz. NH4+ and Cl- ions. NH4+ exists in equilibrium with ammonia (NH3). Cell membranes are relatively impermeable to ionized ammonia NH4+, whereas un-ionized NH3 passes tissue barriers with ease. NH3 is normally present in all tissues constituting a metabolic pool (IPSC, Environ. Health Criteria 54, Ammonia, 1986). Chloride ions are also present in all tissues.

 

Metabolism 

Ammonium chloride rapidly dissociates in biological fluids to yield the ammonium ion (NH4+) and chloride ion (Cl-). Ammonium ions then reach equilibrium with ammonia (NH3) in a pH-dependent manner. Oral administration of ammonium chloride to volunteers caused transient increases in blood-ammonia (IPSC, Environ. Health Criteria 54, Ammonia, 1986). In rats, plasma chloride and urinary ammonia levels were also transiently increased after oral administration (Lina, 2004). Nitrogen arising from ammonium chloride is incorporated into amino acids and proteins. Human volunteers receiving a protein reduced diet were exposed to orally radio-labelled ammonium chloride. Only 35 % of applied radioactivity was excreted. Volunteers on a normal diet however, excreted 70 % of the radioactivity. In the liver, NH4+ ions are transformed into urea.

 

Excretion

In the liver, ammonia is transformed to urea which is then excreted via urine. Faecal excretion is not significant. The major routes for chloride excretion are perspiration and in urine. Due to the physico-chemical properties of the test item, no bioaccumulation is expected.