Neurotoxic effects of combined exposures to aluminum and mercury in early life (infancy)

Aluminum and mercury are environmentally ubiquitous. Individually they are both neurotoxic elements with shared neuro-pathogenic pathways: oxidative stress, altered neurotransmission, and disruption of the neuroendocrine and immune systems. In the infant, Al and Hg differ in type of exposure, absorption, distribution (brain access), and metabolism. In environmentally associated exposure (breast milk and infant formulas) their co-occurrences fluctuate randomly, but in Thimerosal-containing vaccines (TCVs) they occur combined in a proprietary ratio; in these cases, low-doses of Thimerosal-ethylmercury (EtHg) and adjuvant-Al present the most widespread binary mixture in less developed countries. Although experimental studies at low doses of the binary Hg and Al mixture are rare, when studied individually they have been shown to affect neurological outcomes negatively. In in vitro systems, comparative neurotoxicity between Al and Hg varies in relation to the measured parameters but seems less for Al than for Hg. While neurotoxicity of environmental Hg (mainly fish methyl-Hg, MeHg) is associated with neurobehavioral outcomes in children, environmental Al is not associated, except in certain clinical conditions. Therefore, the issues of their neurotoxic effects (singly or combined) are discussed. In the infant (up to six months) the organic-Hg and Al body burdens from a full TCV schedule are estimated to reach levels higher than that originating from breastfeeding or from high aluminum soy-based formulas. Despite worldwide exposure to both Al and Hg (inorganic Hg, MeHg, and Thimerosal/EtHg), our knowledge on this combined exposure is insufficient to predict their combined neurotoxic effects (and with other co-occurring neurotoxicants).