Pentapotassium triphosphate

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
Limited toxicokinetic data are available and therefore an assessment has been made based on the available data only.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

TEST MATERIAL: Pentapotassium triphosphate

Pentapotassium triphosphate is also known under the following synonyms: Potassium triphosphate; Potassium tripolyphosphate; triphosphoric acid, pentapotassium salt. The triphosphate ion is a condensed phosphate group with two P-O-P bonds and has an “inner phosphorus” and two “terminal phosphorus”. The triphosphoric acid can undergo ionisation with loss of H+ from each of the 5 –OH groups (one on the inner P, two on each terminal P) and therefore can occur in the -1, -2 -3, -4 or -5 state. The degree of ionisation is dependent upon the associated cations and the ambient pH (if in solution).

In the substance analysed here, all hydrogen ions are replaced by potassium ions which are ubiquitous and essential to all known living organisms. If dissolved in water potassium cations and the triphosphate anion will dissociate.

Pentapotassium triphosphate (KTPP, K5P3O10) has a molecular weight of 448.41 g/mol. The water solubility is high (45.7 % w/w). A partition coefficient cannot be derived as the substance is inorganic, highly ionised and extremely water soluble. Solubility in fat or organic solvents is negligible. After dissolution of KTPP in neutral, unbuffered water the pH is 9.1 and the substance generates a high buffer capacity. Abiotic hydrolysis is pH dependent (half-lifes: 6.25 h at pH 1, 14.5 d at pH 4, > 1 y at pH 7 and higher). Biotic hydrolysis is fast through ubiquitous alkaline phosphatase activity in micro- and macroorganisms.

 

Because of the ionic nature of KTPP the passive passage across biological membranes will be negligible. However as potassium is a key element in various cellular processes its import and export over cell membranes is regulated via pore systems and usually tightly regulated. Triphosphate is an anion that does not usually diffuse freely in cells and organisms. Nevertheless, it can be expected that every now and then a triphosphate molecule is freed from Nucleotide triphosphates by attack from a water molecule. The triphosphate would then probably be cleaved by one of the different members of the alkaline phosphatase family which are present in all tissues to yield diphosphate (pyrophosphate) and orthophosphate. Diphosphate is subsequently cleaved by the same enzymes into two orthophosphate groups.

Triphosphates are registered as food additives under the No. E 451 and are used in the food chemistry as emulsifiers, stabiliser and buffering agents.

 Absorption

General:

The cation potassium are essential for cellular life, therefore regulated uptake into cells will take place via the typical cellular uptake mechanisms specific for the respective ions. As a tightly regulated equilibrium of this ion is crucial for the functioning of normal cells (i. e. neuronal signal transduction, formation of the membrane potential of all living cells) the amount of uptake is generally tightly regulated. Triphosphate on the one hand is negatively charged hence a passive diffusion across cell membranes is not possible. A triphosphate specific transport protein has not been reported in the literature.

Oral / intestinal absorption:

- Cations: After sodium uptake into the brush-border epithelial cells Na+/K+ ATPase pumps sodium ions out again into the lumen while importing potassium ions under consumption of energy in form of ATP thereby keeping up a steep electrochemical gradient. In addition passive transport of potassium might occur through tight junctions and the lateral spaces and is paracellular. Pinocytosis and other vesicle transport systems can also have an influence on potassium homeostatis and fluxes.

Transfer of potassium to the blood circulation system and homeostatsis of the ion in other tissues are well regulated and similarly complex as the above stated uptake mechanisms and are broadly described in the general biochemical and medical literature.

Recommended daily intake of Potassium is 4,700 mg/d/person for young adults (Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. www. nap. edu.).

- Triphosphate: As stated above diphosphate is rapidly transferred into orthophosphate by intestinal alkaline phosphatase. So the majority of triphosphate is probably absorbed as orthophosphate. In addition direct uptake of triphosphate via diffusion or pinocytosis might add to the total uptake Intracellular alkaline phosphatise activity will then probably lead to formation of orthophosphate.

The bioavailability of orthophosphate from triphosphate has also been shown by Feldheim et. A. 1985 (Feldheim W and Hesselbach C, 1985, Untersuchungen zum Calcium- und Phosphorstoffwechsel beim Mensche/Studies on Calcium and Phosphorous Metabolism in Man. 3rd Communication: Absorption Behaviour in Phosphates of different Chain Length in Miniature Pigs, Aktuelle Ernährungsmedizin 10(1); 30 - 33, 1985, Institut für Humanernährung der Universität Kiel). There supplementation of a basic diet with 1 – 3 g of either disodium hydrogenorthophosphate or pentasodium triphosphate (STPP) lead to comparable uptake and excretion of orthophosphate in mini pigs.

Comparable results in rats were found by Matsuzaki 2001(Greater effect of dietary potassium tripolyphosphate than of potassium dihydrogenphosphate on the nephrocalcinosis and proximal tubular function in female rats from the intake of a high-phosphorus diet. Matsuzaki H, Masuyama R, Uehara M, Nakamura K, Suzuki K. Biosci Biotechnol Biochem. 2001 Apr;65(4):928-34.). No significant differences in phosphate uptake distribution or excretion were seen when phosphorous was administered at normal levels in the diet (100 mmol phosphorus per kg diet) either via potassium dihydrogenorthophosphate or via KTPP. At high doses (400 mmol phosphorus per kg diet) nevertheless induced nephrocalcinosis was more severe with KTPP as phosphorous source.

Respiratory tract:

A particle size distribution study has shown for KTPP that > 60 % of the particles are < 75 µm. This indicates that absorption via inhalation of the substance is well possible as particles at the size of < 10 µm are respirable and at the size of < 4 µm are able tothe alveoli.

Based on the general considerations above an uptake of the cation potassium is likely, though the amount is expected to be rather low as compared to oral uptake. Absorption of triphosphate is rather unlikely via the inhalation route.

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.

Dermal:

Potassium ions can penetrate the skin to some extent but the absorption is much lower then via the oral route. The triphosphate is, depending on the pH, highly to very highly ionised which reduces drastically the potential to penetrate the lipid rich environment of the striatum corneum. Therefore dermal uptake of triphosphate will probably be minimal.

Distribution

 Sodium and Potassium are natural components of blood as free ions and their distribution and circulations is as precisely regulated as their uptake. Triphosphate is not expected tothe blood circulation but cleaved either by extracellular or intracellular alkaline phosphatases after uptake in the intestine (or in the lung). Triphosphate uptake obviously leads to an enhanced nephrocalcinosis (i. e. calcium phosphate deposition) as comparable orthophosphate uptake. But the reason for this effect is not clarified to date (see Matsuzaki 2001 above).

Metabolism

Both ions (potassium and triphosphate) are inorganic and stable to reduction or oxidation in biological systems. Triphosphate is hydrolysed to orthophosphate by ubiquitous alkaline phosphate activity (different iso-enzymes in different tissues). Orthophosphate then takes part in various physiological processes including formation of Deoxyribonucleotide phosphates (e. g. AMP, cAMP, ADT, ATP).

Excretion

 Assuming homeostasis of potassium as indispensable nutrient in a healthy organism the same amount of the ion is excreted as taken up. Potassium and orthophosphate formed from triphosphate are generally excreted mainly via kidneys but also via feces and sweat.

Toxicity data

The above stated assumptions are supported by the findings in the toxicological studies. Most of the studies results are derived with pentasodium triphosphate (STPP). Both sodium and potassium cations are ubiquitous in natural waters and are considered to possess similar toxicological and ecotoxicological profiles due in part to their similar behaviour and their existence as essential micronutrients. Therefore study results derived with STPP are expected to be valid also for KTPP.

Oral toxicity of KTPP was above 2000 mg/kg bw in the rat. Acute dermal toxicity was not found for STPP, all animals survived doses up to 4.64 g/kg bw. This underlines the low potential of triphosphate to penetrate the skin. This is supported by the complete absence of skin irritation in an adequate test in rabbits for KTPP and complete absence of skin sensitisation effects in an adequate LLNA test for STPP. For acute inhalation toxicity it can be stated that at the highest achievable concentration of 0.39 mg/L no mortality occurred in rats. Only signs consistent with exposure to an irritant dust were seen: partial closing of the eye, exaggerated respiratory movements, restless behaviour and excessive grooming seen in all exposed rats.

The available oral repeated dose studies for STPP in dog and rat confirm that the kidneys (chronic tubular nephropathy) are the primary target organ of subchronic oral toxicity of triphosphates (NOAEL in rats 225 mg/kg bw/d). Secondary effects at higher doses are bone growth reduction and anaemia. No effects on reproductive organs or reproductive efficiency were seen at these dose levels.