Iron orthophosphate

Endpoint summary

Description of key information

Iron orthophosphate is poorly absorbed after oral, inhalation and dermal exposure. It has no bioaccumulation potential. Iron and phosphorous are widely distributed in the human body. The excretion of iron is limited as body iron is highly conserved.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

SUMMARY OF THE KNOWN TOXICOKINETICS OF IRON ORTHOPHOSPHATE

  

The process of iron absorption plays the major role in the maintenance of iron homeostasis of the human body because the capacity of the body to excrete iron is extremely limited.

The mechanism of the absorption of iron salts has been extensively studied. Ferric phosphate dissociates into trivalent iron-cations and phosphate anions which are separately absorbed. Iron crosses cell membranes only in the ferrous state (Fe2+); ferric (Fe3+) ions are liberated in the stomach by acid digestion, reduced to the ferrous state, and absorbed. As a result of an intestinal mucosal block only approximately 10% of ingested iron is absorbed. Absorption occurs mostly in the duodenum and upper jejunum, although the entire intestinal tract, including the colon, is able to absorb iron.

The divalent (ferrous) iron is absorbed into the gastrointestinal mucosa and converted to the trivalent (ferric) form, which attaches to ferritin in the intestinal mucosal cell wall. The ferritin-ferric storage complex then passes into the bloodstream and is attached to transferrin. Iron is then carried to the reticuloendothelial cells of the bone marrow for haemoglobin synthesis or to the liver or spleen for storage as ferritin or hemosiderin.

The amount of absorption is variable between individuals and according to the iron status of the individual at that time. It is significantly influenced by a number of factors both diet- and host-related.

Iron absorption is regulated by different mechanisms in the human or animal body. Principal factor in the regulation of iron absorption is the body iron content. The adult human body contains approximately 2.2-3.8 g of iron under iron-adequate conditions. Homeostatic mechanisms of intestinal iron absorption have evolved in such a way that intestinal absorption can be altered and iron may be preferentially supplied to functional compartments in response to deficiency or excess.

60.2% of the iron orthophosphate is smaller than 4 µm. Therefore, iron orthophosphate particles can be inhaled and likely reach the alveolar region of the respiratory tract since they are below 15 µm (ECHA, 2017). Besides, the substance is inorganic and therefore would not have the potential to be absorbed directly across the respiratory tract epithelium non-resorbed particles in the oral-nasal cavity, the airways and the lungs will mainly be cleared from the lungs by the mucocillary mechanism and swallowed and thus absorbed there.

No data are available on dermal absorption of iron orthophosphate. If no data is available, basic physico-chemical information should be taken into account, i.e. molecular mass and lipophilicity (log P) (ECHA, 2017). Following, a default value of 100% skin absorption is generally used unless molecular mass is above 500 and log P is outside the range [-1, 4], in which case a value of 10% skin absorption is chosen. Due to the special properties of metals and their inorganic salts an approach consistent with the methodology proposed in HERAG guidance for metals is used:

In contrast to the default 10% or 100% values for substances with no further information, the currently available scientific evidence on dermal absorption of metals (predominantly based on the experience from previous EU risk assessments) yield substantially lower values as described subsequently:

Measured dermal absorption values for metals or metal compounds in studies corresponding to the most recent OECD test guidelines are typically 1% or even less. Therefore, the use of a 10% default absorption factor is not scientifically supported for metals. This is corroborated by conclusions from previous EU risk assessments (Ni, Cd, Zn), which have derived dermal absorption rates of 2% or far less (but with considerable methodical deviations from existing OECD methods) from liquid media - more recent and guideline-conform testing with refined accuracy has even yielded dermal absorption rates at or below 0.3% (Cu, Pb, Sb). Thus, on a preliminary basis, currently a default dermal absorption rate of 1% for absorption from liquid aqueous media would appear reasonable and adequately conservative for regulatory purposes based on a comparative assessment of the results from reliable, guideline-conform dermal absorption studies.

However, considering that under industrial circumstances many applications involve handling of dry powders, substances and materials, and since dissolution is a key prerequisite for any percutaneous absorption, a factor 10 lower default absorption factor may be assigned to such “dry” scenarios where handling of the product does not entail use of aqueous or other liquid media. This approach was taken in the EU risk assessment on zinc. A reasoning for this is described in detail elsewhere (Cherrie and Robertson, 1995), based on the argument that dermal uptake is dependent on the concentration of the material on the skin surface rather than it’s mass.

The following default dermal absorption factors for metal cations and thus for iron ions are therefore proposed:

From exposure to liquid/wet media: 1.0%

From dry (dust) exposure: 0.1 %

Iron orthophosphate is an inorganic sold which has low solubility in water. The bioavailability compared to other iron sources is very poor. On a comparative scale of bioavailability where ferrous sulphate is 100, ferric phosphate was found to have an average relative bioavailability, to man, of 11-50% (although other data reviews report this figure to be ca. 24).

There is no potential for accumulation of ferric phosphate in the human or animal body.

Iron and phosphorus are widely distributed in the body. Approximately two thirds of the body iron is bound to haemoglobin, less than 10% is found in myoglobin. Excessive intracellular iron is bound to the storage protein ferritin – the serum ferritin concentration can be used as an indicator of body iron stores. The concentration of free iron in the blood is extremely low due to the high affinity binding of iron to transferrin.

The excretion of iron is limited as body iron is highly conserved. Renal iron excretion is reported to be as low as 0.1 mg per day and a further 0.2-0.3 mg is lost daily from the skin as a result of sloughing of mucosal enterocytes. Menstrual losses are variable.

 

References:

Cherrie and Robertson (1995): Biologically relevant assessment of dermal exposure; Ann. Occup. Hyg. 39, 387-392

ECHA (2017): Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c: Endpoint specific guidance, Version 3.0, June 2017

HERAG (2007);HERAG fact sheet - assessment of occumpational dermal exposure and dermal absorption for metals and inorganic metal compounds; EBRC Consulting GmbH / Hannover /Germany; August 2007; http://www.ebrc.de/downloads/HERAG_FS_01_August_07.pdf)