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Description of key information

No studies are available. 
A limited toxicokinetic assessment based on available physico/chemical properties of phosphoric acid indicates oral and dermal absorption factors of 50 to 100% and an inhalation absorption factor of 100%. Phosphoric acid is furthermore not considered to have bioaccumulative potential. This qualitative judgement on the toxicokinetic behaviour based on physico-chemical characteristics follows the recommendations of ECHA (ECHA Endpoint specific guidance, Chapter R.7c; section R.7.12.2.1). Two supporting metabolism studies are available (Bonting, 1952 and 1956).

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

ABSORPTION

Oral absorption:

The dissociation constants for phosphoric acid have been determined to be pKa1 = 2.1, pKa2 = 7.2 and pKa3 = 12.3. As such, the predominant forms in biological systems will be H2PO4(-) and HPO4(2-).

These anions are present and can be absorbed in the human intestine; which has a pH in the range of 5 to 8 depending upon location. The absorption of ionised acids is favoured at pHs below the PKa and as such phosphoric acid is mainly absorbed in the jejunum (pH6-7) by passive diffusion or active transport facilitated by vitamin D (EFSA, 2005).

The main mechanism for absorption of small water soluble molecules in the GI tract is passage through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. Oral absorption might thus be as high as 100% if the inorganic phosphate intake is low, but will decrease with higher loads. Dietary compounds are also expected to influence the rate and extend of phosphate absorption via the GI tract. The principle dietary factor influencing phosphate uptake from the lumen of the GI tract is intestinal calcium concentration, which can reduce phosphate bioavailability by forming insoluble complexe (Heaney, 2012) . For the purposes of REACH, an oral absorption of 100% is therefore proposed.

 

Respiratory absorption:

Although phosphoric acid is a solid at room temperature, the substance is hygroscopic and no airborne particles are to be expected. Although in general, hydrophilic substances are effectively removed from the air in the upper respiratory tract, the relevance of this mechanism for phosphoric acid is difficult to predict as the octanol/water partition coefficient is not defined for inorganic substances. Hydrophilic substances also have the tendency to be retained in the aqueous fluids (mucus) lining of the respiratory tract, limiting the systemic uptake. Although based on available physico/chemical data the systemic uptake of phosphoric acid might be limited, a worst-case absorption factor of 100% is proposed for inhalation.

Dermal absorption:

Absorption via the dermal route is expected to be significant as the substance has a low molecular weight and is very water soluble. It may however be too hydrophilic to cross the lipid rich environment of the stratum corneum, but due to the absence of the octanol/water partition coefficient, this is difficult to predict. As phosphoric acid is corrosive to skin, any skin damage might enhance penetration of the substance. It is generally accepted that the dermal absorption will not be higher compared to the oral absorption. As a default value of 100% skin absorption should be used for substances with molecular mass below 500, the dermal absorption factor is set at 100% as for the oral absorption.

 

DISTRIBUTION

Wide distribution throughout the body is to be expected as small water-soluble molecules and ions will diffuse through aqueous channels and pores. Depending on the structure in which the phosphate is covered, the uptake by cells might either be via active or passive transport. Serum phosphate levels are tightly regulated via homeostatic mechanisms involving the vitamin D endocrine system and parathyroid hormone (PTH). Accumulation of test material in body fat is not favourable.

 

METABOLISM

The very high water solubility of the test material does suggest it is unlikely to be any metabolism.

 

EXCRETION

Excretion will be via urine as characteristics favourable for urinary excretion are low molecular weight (below 300 in the rat), good water solubility, and ionisation of the molecule at the pH of urine.

Phosphoric acid as inorganic phosphate is an essential constituent of the human organism, not only in the bones and teeth, but also in many enzyme systems. Phosphorus plays an important role in carbohydrate, fat and protein metabolism.

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