Magnesium bis(dihydrogenorthophosphate)

Endpoint summary

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 bis(dihydrogenorthophosphate) 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 bis(dihydrogenorthophosphate) 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).

TEST MATERIAL: Orthophosphates (with calcium or magnesium cation)

 

Group 1ii, are orthophosphates. The orthophosphate stems from phosphoric acid (H3PO4) which can undergo ionisation with loss of H⁺ from each of the three –OH groups and therefore can occur in the -1, -2 or -3. The degree of ionisation is dependent upon the associated cation and the ambient pH (if in solution).

The ionic form of the Group 1ii alkali metals is M²⁺. Also as with the two alkali metals magnesium and calcium are ubiquitous and essential to all known living organisms.

The Inorganic orthophosphates were grouped based on the structure of the phosphate ions firstly, then grouped accordingly to their cation identity. Group 1ii includes the following substances: Calcium bis (dihydrogenorthophosphate) (MW: 234-236), Calcium hydrogenorthophosphate(MW:136-138), Tricalcium bis(orthophosphate) (MW:310), Tricalcium phosphate(MW:502), Magnesium hydrogenorthophosphate(MW:120), Trimagnesium bis(orthophosphate) (MW:262) and Magnesium bis (dihydrogenorthophosphate) (MW:218-219).

No low log oil/water partition coefficient value was determined for Group 1ii substances as they are inorganic phosphates, therefore the passive passage across biological membranes will be negligible. However as calcium, 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.

Particle size distribution studies have shown that a number of the substances have a considerable fraction of the particles with a diameter less than 45 µm, with the exception of tricalcium phosphate and magnesium bis (dihydrogenorthophosphate) with <1% of the particles less than 500µm and 250µm, respectively. This indicates that absorption via inhalation of the substance will be minimal as the particle sizes of < 10 µm which is respirable and of < 4 µm which is the cut-off for alveoli reaching particles. Also the substances are not lipophilic therefore would not have the potential to be absorbed directly across the respiratory tract epithelium. However their nature as physiological substance will probably lead to some absorption via the respiratory tract. Non-resorbed particles in the oral cavity, the thorax 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.

 The balance of the calcium phosphate metabolism is tightly regulated by the hormones parathormone, calcitriol (vitamin D) und calcitonin. Uptake of magnesium, calcium and phosphate in the intestine is mainly mediated mainly by specific transmembrane transport proteins. Nevertheless other mechanisms like passive diffusion or pinocytosis may contribute also to some extent to absorption of the ions.

Typical intestinal uptakes for magnesium, calcium and phosphate from the diet are 360, 800, 1200 mg/person/d (http: //www. uptodate. com, SCF/CS/NUT/UPPLEV/64 Final 23 April 2003 Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Calcium, ec. europa. eu/food/fs/sc/scf/out105_en. pdf, Kidney Int. 2008 Jul;74(2):148-57. Epub 2008 Apr 30. Hyperphosphatemia of chronic kidney disease. Hruska KA, Mathew S, R, Qiu P, Pratt R.).

The very high water solubility suggests that the substance is too hydrophilic to cross the lipid rich environment of the striatum corneum. Also the molecular weight of >100 and the extremely hydrophilic nature of the substance leads to the conclusion that dermal uptake of the substance will be minimal.

Distribution

Magnesium and phosphate are dissolved as ions in blood. Calcium is partly dissolved as an ion while about 50 % is bound to albumin in blood. As all three ions are indispensable to life their distribution is tightly regulated systemically as well as intra-cellular.

Metabolism

All three 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 and calcium are complexed to important biological molecules (e. g. Mg: DNA, ATP, etc.; Ca: calmodulin, calbindin, etc.).

Excretion

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