The European Union’s REACH Regulation requires determination of potential health and environmental effects of chemicals in commerce. The present case study examines the application of REACH guidance for health hazard assessments of three high production volume (HPV) aluminium (Al) substances: metallic aluminium, aluminium oxide, and aluminium hydroxide. Among the potential adverse health consequences of aluminium exposure, neurotoxicity is one of the most sensitive targets of Al toxicity and the most critical endpoint. This case study illustrates integration of data from multiple lines of evidence into REACH weight of evidence evaluations. This case study then explains how those results support regulatory decisions on classification and labelling. Challenges in the REACH appraisal of Al compounds include speciation, solubility and bioavailability, application of assessment factors, read-across rationale and differences with existing regulatory standards. Lessons learned from the present case study relate to identification and evaluation of toxicologic and epidemiologic data; assessing data relevance and reliability; development of derived no-effect levels (DNELs); addressing data gaps and preparation of chemical safety reports.

The REACH registration process: A case study of metallic aluminium, aluminium oxide and aluminium hydroxide.

Aluminum bone toxicity in infants may be promoted by iron deficiency.

Local and Systemic Hypoxia as Inductors of Increased Aluminum and Iron Brain Accumulation Promoting the Onset of Alzheimer’s Disease

Aluminum is environmentally ubiquitous, providing about 8% of the earth's crust. It can be absorbed from the gastrointestinal tract and lungs. Excretion is mainly by the kidneys, probably as aluminum citrate. Aluminum is a well-known neurotoxicant. Significant accumulation in the human body has been attributed to aluminum in dialysis fluids and intake of aluminum-containing drugs by those with significant renal impairment and to occupational exposure in some industrial settings. Accumulation in patients with renal impairment resulted in dialysis encephalopathy that was often fatal; a problem now well recognized and usually avoided. The population at greatest risk for aluminum intoxication are those with renal impairment, particularly premature infants receiving parenteral nutrition. Exposure-related cognitive and motor impairments have been observed in welders whose aluminum urine concentrations were ≥100 μg/L. The upper reference limit among nonexposed individuals is 15 μg/L urine. There is no consensus that aluminum is a significant contributor to Alzheimer's disease or good evidence that vaccines contribute to autism spectrum disorder. Occupational aluminum powder exposure has resulted in pulmonary fibrosis. Asthma has been associated with aluminum sulfate, aluminum fluoride, and potassium aluminum tetrafluoride inhalation, and exposure to the complex environment in potrooms during electrolytic aluminum production. Cancer and ischemic heart disease have been observed among aluminum production workers. However, it is unlikely that aluminum is the cause of these diseases. 

Aluminum

Aluminum is an element found in nature and in cosmetic products. It can interfere with the metabolism of other cations, thus inducing gastrointestinal disorder. In cosmetics, aluminum is used in antiperspirants, lipsticks, and toothpastes. The aim of this work is to investigate aluminum bioavailability after accidental oral ingestion derived from the use of a toothpaste containing a greater amount of aluminum hydroxide than advised by the Scientific Committee on Consumer Safety (SCCS). To simulate in vitro toothpaste accidental ingestion, the INFOGEST model was employed, and the amount of aluminum was measured through the ICP-AES analysis. Tissue barrier integrity was analyzed by measuring transepithelial electric resistance, and the tissue architecture was checked through light microscopy. The margin of safety was also calculated. Overall, our results indicate that the acute exposure to aluminum accidentally ingested from toothpastes is safe for the final user, even in amounts higher than SCCS indications.

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Innovative In Vitro Strategy for Assessing Aluminum Bioavailability in Oral Care Cosmetics

The fractional uptake of ingested aluminium and aluminium compounds (aluminium citrate, aluminium nitrate, aluminium chloride, aluminium sulphate, aluminium hydroxide, aluminium oxide, aluminium metal, powdered aluminium pot electrolyte, acidic sodium aluminium phosphate (SALP), basic sodium aluminium phosphate (Kasal), sodium aluminium silicate and FDC 002% for aluminium oxide; 004% for powdered pot electrolyte; 012% for sodium aluminium silicate; and 009% for FD&C red 40 aluminium lake For aluminium metal, SALP and Kasal the amount of 26Al present in the rats was insufficient to determine uptake and was less than 003% The results produced for aluminium citrate, aluminium hydroxide and aluminium sulphate are close to those published for man

N.D. Priest

Papers

The bioavailability of ingested 26Al-labelled aluminium and aluminium compounds in the rat.