Spinel (Mg(AlO2)2)

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Remarks:

rat

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there is no or no significant human exposure

Justification for type of information:

Justification for waiving of developmental toxicity testing (Spinel) According to section 1 of REACH Regulation (EC) Annex XI, testing for pre-natal developmental toxicity does not need to be conducted if testing does not appear scientifically necessary. Aluminium is firmly bound in the Spinel lattice such that it does 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 Spinel 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 Spinel was tested. These in vitro tests in intestinal liquid with the Spinel mineral asserted the bioinert character of the test substance. Considering the above mentioned factors, Spinel 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 Spinel is the inhalative one which is also of no relevance due to the bio-inertness of the Spinel mineral. The determined bioaccessiblity of aluminium for Spinel in the lung is 1.11 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. 0.022 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 40 times the potential additional “burden”. Therefore, it clearly follows that the potential systemic increase of aluminium from inhalation of Spinel is marginal. Considering the above mentioned factors, Spinel is obviously devoid of toxicity via the oral 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. For developmental toxicity of the Spinel mineral, the aluminium ion (the metal ion of toxicological concern in the Spinel 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. It is therefore unlikely to occur with the insoluble Spinel which is not soluble in the digestive tract and in alveolar liquid. Spinel 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 Spinel will not be absorbed dermally.

Materials and methods

Test animals

Species:

rat

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified