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EC number: 231-633-2
CAS number: 7664-38-2
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.184.108.40.206). Two supporting metabolism studies are available (Bonting, 1952 and 1956).
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.
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.
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
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.
The very high water solubility of the test material does suggest it is
unlikely to be any metabolism.
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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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