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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

An extensive endpoint summary is attached (Attachment to endpoint summary 7_1.pdf). The conclusions are reproduced below.


·        The uptake of iron from the gastrointestinal tract is strictly actively regulated by means of a complicated mechanism to prevent iron overload and its pathological sequela. This means that in healthy humans the amount of absorbed iron is kept at bay in case of an increased oral intake of absorbable iron. In other words, the iron status of healthy humans is not greatly affected by an increased oral intake.

·        Iron is only absorbed in the form of iron ions or bound to haem molecules. The regulation of iron absorption is restricted to the ionic form.

·        After absorption, systemic exposure to free iron is very low, because the iron is bound to transferrin for transport and to ferritin and haemosiderin for storage.

·        Too high iron absorption and iron overload have been observed in humans with a disturbed regulation of iron absorption, i.e. haemochromatosis patients.

·        Iron overload may also occur in humans as a result of repeated blood transfusions. Moreover, it is associated with Bantu siderosis. This pathological condition is probably not the result of high iron intake levels, but may depend on a genetic defect and/or alcohol consumption.

·        Mammals differ strongly as regards the quantitative aspects of the regulation of iron uptake, humans being much more conservative than rodents used in toxicological experiments, in particular rats. It has been demonstrated that uptake and loss of iron are at least 10 times higher in rats than in humans on a per-kg-bw basis.

·        The overall loss and uptake of iron by humans is about 0.9 -1.5 mg/day; the total amount of iron present in the body is about 3 -4.5 g; about 2.5 g is present in the red blood cells; iron intake via food amounts to about 10 -20 mg of which about 5 -10% is absorbed. The daily absorption/loss represents less than 0.1% of the total iron load of the human body.

·        Iron overload can be induced in rats by high metallic iron levels in their feed (several percent; see also repeated-dose studies summarized in IUCLID Section 7.5.1). The much more conservative human iron regulation makes it difficult to extrapolate these high levels to humans.

·        Metallic iron particles are used for iron supplementation and fortification in medicine and nutrition. Moreover, they are used to induce iron overload in rats.

·        It has unambiguously been demonstrated that dissolution and ionization at low pH levels (<2) in the gastric juice is necessary to make the iron from metallic iron absorbable and thus available for systemic exposure. Metallic iron particles can thus be regarded as a slow-release formulation of iron ions, which explains their low oral acute toxicity in comparison to a soluble iron salt as ferrous sulfate.

·        Metallic iron particles are too large (MMAD >1 µm) to be translocated directly from the alveoli to other organs via the epithelium of the alveoli, a systemic exposure route postulated for ultrafine particles and nanoparticles (MMAD <0.1 µm).

·        In the absence of direct translocation from the lungs, systemic exposure can only occur by the ingestion of material that was cleared via the mucociliary tract, either as such or after phagocytosis by alveolar macrophages.

·        Assuming that 50% of inhaled metallic iron is available for secondary ingestion, a secondary ingestion of 15 and 50 mg iron occurs at the exposure limits of respirable and inhalable inert dust respectively.