Orthophosphoric acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Qualitative judgement on the toxicokinetic behaviour based on physico-chemical characteristics

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Phosphoric acid is an inorganic substance and thus some physico-chemical characteristics (like the octanol/water partition coefficient) are not defined. This limits the reliability of the qualitative judgement.

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Guideline:

other:

Principles of method if other than guideline:

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).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Orthophosphoric acid

EC Number:

231-633-2

EC Name:

Orthophosphoric acid

Cas Number:

7664-38-2

Molecular formula:

H3O4P

IUPAC Name:

phosphoric acid

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Following the pKa of phosphoric acid (pKa1 = 2.1, pKa2 = 7.2, pKa3 = 12.3) the predominant forms in biological systems will be H2PO4(-) and HPO4(2-), including the human intestine with pH in the range of 5 to 8. Predominant mechanism for absorption of small well 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. An oral absorption between 50 and 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 will be significant as the substance has a low molecular weight and is very well 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 50 - 100% as for the oral absorption.

Details on distribution in tissues:

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. The phosphate levels are regulated via homeostasis.

Details on 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 ionization of the molecule at the pH of urine.

Any other information on results incl. tables

Phosphoric acid 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.

Applicant's summary and conclusion

Conclusions:

A qualitative judgement on the toxicokinetic behaviour was performed based on physico-chemical characteristics. Phosphoric acid is an inorganic substance and thus some physico-chemical characteristics (like the octanol/water partition coefficient) are not defined, limiting the possibilities of a qualitative assessment. Absorption factor of 100% is proposed for inhalation and 50-100% for oral and dermal absorption.
Phosphoric acid is not considered to have bioaccumulative potential as it is highly soluble in water and phosphate levels in the body are regulated via homeostasis.