Aluminum iron oxide (Al2FeO4)

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

Justification for waiving of developmental toxicity testing (Hercynite) According to section 1 of REACH Regulation (EC) Annex XI, testing for developmental toxicity does not need to be conducted if testing does not appear scientifically necessary. Aluminium and iron are firmly bound in the Hercynite lattice such that they do not have a relevant solubility which is a precondition for bioavailability. This was confirmed by solubility tests in physiological media (lung surfactant and digestive tract). Solubilisation is usually required for absorption across biological membranes, i.e. poorly soluble forms of minerals have per se also low bioavailability for their respective ions. Due to the insolubility of Hercynite in the digestive tract, systemic toxicity after oral uptake is not to be expected from this substance. Bioavailability is the main important factor that affects oral toxicity of a chemical substance. It is defined as the fraction of an ingested dose that crosses the gastro-intestinal epithelium and becomes systemically available for distribution to internal target tissues and organs. Since the gut wall presents a substantial barrier to prevent uptake of metal ions from food in general and of non essential ions in particular the respective solubility of Hercynite was tested. These in vitro tests in intestinal liquid with the Hercynite mineral asserted the bioinert character of the test substance. Considering the above mentioned factors, Hercynite is obviously devoid of toxicity via the oral route, i.e. developmental toxicity is no relevant toxicological endpoint. The other most appropriate route of exposure to Hercynite is the inhalative one which is also of no relevance due to the bio-inertness of the Hercynite mineral. The determined bioaccessiblity of aluminium for Hercynite in the lung is 1.0 x 10-4 %. Assuming a respiratory volume of ca. 10 m3 per worker’s shift, a blood volume of ca. 5 l, and an occupational exposure limit (OEL-TWA) of 10 mg/m3 for total (inert) dust (respirable fraction; TRGS 900: Technical Guidance for dangerous substances: Airborne exposure limits), the mass of aluminium that could be solubilised in the lung would be ca. 0.02 μg/l of blood. The normal serum concentration of aluminium (background value) of the average adult is 1 to 2 μg/l, i.e. more than very roughly 50 times the potential additional “burden”. Therefore, it clearly follows that the potential systemic increase of aluminium from inhalation of Hercynite is marginal. The determined bioaccessiblity of iron for Hercynite in the lung is less than 1.422 x 10-6 %. Assuming a respiratory volume of ca. 10 m3 per worker’s shift, a blood volume of ca. 5 l, and an occupational exposure limit (OEL-TWA) of 10 mg/m3 for total (inert) dust (respirable fraction; TRGS 900: Technical Guidance for dangerous substances: Airborne exposure limits), the mass of iron that could be solubilised in the lung would be ca. 0.0002 μg/l of blood. In humans, around 2/3 of iron are available as functional iron in the form of haemoglobin in the erythrocytes (approximately 5 x 106 erythrocytes/mm3 blood). The molecular weight of haemoglobin is approximately 64 500. As 1 g haemoglobin contains 3.4 mg iron (or 1 mol haemoglobin 4 mol iron), that can bind 1.34 ml O2 ,1 ml blood with a haemoglobin concentration of 15 g/100 ml (2.3 mmol/l) contains approximately 0.5 mg (9 μmol) iron. This means that the healthy adult has about 2.5 g (45 mmol) haemoglobin iron in his 5 l blood, i.e. more than 1 x 1010 times the potential additional „burden“. Considering the above mentioned factors, Hercynite is obviously devoid of toxicity via the oral, dermal and inhalative route, i.e. developmental toxicity is no relevant toxicological endpoint. Aluminium toxicity depends on the solubility of aluminium and the presence of biologically active forms of aluminium, i.e. aluminium ions. When there is no relevant systemic exposure, there can be no response regardless of the type of toxicological endpoint. To put figures into perspective potential aluminium intake in general needs to be compared with the daily unavoidable oral intake of aluminium from foodstuff which is approximately 20-40 mg per person and also with the ADI of 1 mg/kg which is thought by WHO`s JECFA to be without any health concern. Iron is an essential element in human nutrition. Estimates of the minimum daily requirement for iron depend on age, sex, physiological status, and iron bioavailability and range from about 10 to 50 mg/day. For developmental toxicity of the Hercynite mineral, the aluminium ion (the metal ion of toxicological concern in the Hercynite crystal lattice) will have to be made bioavailable to the target organs and tissues in sufficient concentration to cause the toxic effect. This requires that the aluminium will have to be bioavailable by absorption via relevant routes of exposure. The toxicity threshold has to be reached before the maximum tolerated dose of the maternal animal prevents higher exposure. It is therefore unlikely to occur with the insoluble Hercynite which is not soluble in the digestive tract and in alveolar liquid. Hercynite is insoluble in water and not fat soluble, consequently it is not expected to be absorbed through the skin. In particular also cations from solubilised Hercynite will not be absorbed dermally.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

dialuminium iron tetraoxide, spinel type

EC Number:

924-056-9

Cas Number:

1302-61-0

Molecular formula:

Al2FeO4

IUPAC Name:

dialuminium iron tetraoxide, spinel type

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified