Magnesium hydrogenorthophosphate

Endpoint summary

Description of key information

In the absence of specific data on the ADME of magnesium hydrogenorthophosphate, its physicochemical properties and relevant toxicity data (where available)

were assessed for insights into likely ADME characteristics. Although magnesium hydrogenorthophosphate has a MW >100 g/mol (120 g/mol) and is moderately soluble in water it is considered that absorption via the oral route is likely to be moderate due to its nature to ionize into phosphate and magnesium. Phosphate and magnesium are important biological molecules which are tightly regulated systemically as well as intra-cellular. Absorption of magnesium hydrogenorthophosphate itself via inhalation route will be low due to its molecular weight and moderate solubility. Non-resorbed particles in the oral-nasal cavity, airways and lungs will be transferred to the gastrointestinal tract with the mucus and absorbed there. Therefore, the absorption from the gastrointestinal tract will contribute to the total systemic burden of the substance that is inhaled. Low dermal absorption is expected. Based on a precautionary approach, an absorption default value of 100% is considered appropriate for oral and inhalation route and 50% for the dermal route. Wide tissue distribution of absorbed magnesium hydrogenorthophosphate itself is not expected but the ionic forms of phosphate and magnesium are widely distributed due to the indispensable character of phosphate and magnesium. The suggested metabolism involves hydrolysis to the more soluble and polar products, magnesium and phosphate ions. Due to these factors, urinary excretion as well as via faeces and sweat is the most probable route of elimination and bioaccumulation is unlikely.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic behaviour of magnesium hydrogenorthophosphate (CAS 7757-87-1) has been investigated.

Therefore, in accordance with Annex VIII, Column 1, Section 8.8.1, of Regulation (EC) No 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2014), assessment of the toxicokinetic behaviour of magnesium hydrogenorthophosphate is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the physico-chemical and toxicological properties according to Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2014).

Magnesium hydrogenorthophosphate is a solid at 20°C with a molecular weight of 120 g/mol and a water solubility of 578 mg/L at 20°C and pH7.4 to 7.6.

 

ABSORPTION

Oral

No specific data regarding oral absorption of magnesium hydrogenorthophosphate were found. ECHA guidance suggests that absorption is considered favourable for substances with a molecular weight (MW) below 500 Daltons (ECHA, 2014). Therefore, the MW (120 g/mol) might be indicative of absorption. For a substance to be absorbed efficiently from the gastrointestinal tract it must be in solution. A recent study report determined the water solubility of magnesium hydrogenorthophosphate to be 578 mg/L at pH 7.4-7.6 whereas at pH4 and pH9 the water solubility increased dramatically (1110 mg/L at pH4 and 817 mg/L at pH9). It could be assumed that magnesium hydrogenorthophosphate dissolves in the gastrointestinal fluids and the substance may (since the MW is below 500) pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water (ECHA, 2014). However, as magnesium and phosphate are key elements in various cellular processes their import and export over cell membranes is regulated via pore systems and usually tightly regulated. No clinical signs or pathological findings were observed following a single oral dose of magnesium hydrogenorthophosphate. So no conclusion regarding absorption can be drawn from this observation. In the absence of specific data to the contrary, a default value of 100% is suggested.

 Inhalation

According to ECHA (2014) guidance, particles with aerodynamic diameters below 100 µm have the potential to be inhaled.

The granulometry study shows that magnesium hydrogenorthophosphate consists of at least 99% of particles with a particle size of <45 µm (considered to be respirable and might reach the thoracic region). As such the particle size distribution indicates substance is an inhalation risk (a significant proportion of the particles are present at < 45 µm).

Therefore magnesium hydrogenorthophosphate particles can be inhaled (ECHA, 2014). Besides, the substance is not lipophilic therefore, would not have the potential to be absorbed directly across the respiratory tract epithelium. However, its nature as physiological substance will probably lead to some absorption via the respiratory tract. Non-resorbed particles in the oral-nasal cavity, the airways and the lungs will be transferred to the gastro-intestinal tract with the mucus and absorbed there. Therefore, absorption from the gastrointestinal tract will contribute to the total systemic burden of the substance that is inhaled. On this basis, a default of 100% is proposed.

Dermal

ECHA guidance suggests that absorption is considered favourable for substances with a MW below 100 g/mol (ECHA, 2014). Therefore, the MW (120 g/mol) suggests dermal absorption is not likely. For a compound to penetrate the stratum corneum, it must be sufficiently water soluble i. e. above 1 mg/L (ECHA, 2014). The aqueous solubility of magnesium hydrogenorthophosphate (578 mg/L) indicates that dermal absorption will be low to moderate to high (ECHA, 2014) but since magnesium hydrogenorthophosphate is an inorganic substance the passive passage across biological membranes will be negligible. In addition, as the test substance is a solid, hindered dermal absorption has to be considered as dry particulates first have to dissolve into the surface moisture of the skin before uptake via the skin is possible (ECHA, 2014). QSAR analysis of magnesium hydrogenorthophosphate suggests a very low dermal absorption rate with an absorption potential of 10%. Due to the moderate soluble character of magnesium hydrogenorthophosphate a conservative approach of a moderate skin absorption of 50% is recommended.

 

DISTRIBUTION/METABOLISM

No data were found regarding the distribution and metabolism for magnesium hydrogenorthophosphate. Looking at the physical/chemical parameters of magnesium hydrogenorthophosphate (MW=120 g/mol, inorganic, moderately soluble) a wide tissue distribution is not assumed (ECHA, 2014). But the structure suggests magnesium hydrogenorthophosphate will slowly ionise to phosphate anions and magnesium species. Phosphate is dissolved as ions in blood. Magnesium is partly dissolved as an ion while about 50% is bound to albumin in blood. As both ions are indispensable to life their distribution is tightly regulated systemically as well as intra-cellular.

Both ions are inorganic and stable to reduction or oxidation in biological systems. Phosphate is condensed to di and triphosphates (e. g. AMP, ADT, ATP). Magnesium is complexed to important biological molecules (e. g. DNA, ATP, etc.).

 

EXCRETION

Assuming homeostasis of these indispensable nutrients the same amount is excreted as taken up. Magnesium and phosphate are generally excreted mainly via kidneys but also via faeces and sweat (varying for the specific ion).

 

References:

ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. Version 2.0, November 2014.