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Manganese (Mn) is an essential mineral. It is present in virtually all diets at low concentrations. The principal route of intake for Mn is via food consumption, but in occupational cohorts, inhalation exposure may also occur (this subject will not be dealt with in this review). Humans maintain stable tissue levels of Mn. This is achieved via tight homeostatic control of both absorption and excretion. Nevertheless, it is well established that exposure to high oral, parenteral or ambient air concentrations of Mn can result in elevations in tissue Mn levels. Excessive Mn accumulation in the central nervous system (CNS) is an established clinical entity, referred to as manganism. It resembles idiopathic Parkinson's disease (IPD) in its clinical features, resulting in adverse neurological effects both in laboratory animals and humans. This review focuses on an area that to date has received little consideration, namely the potential exposure of parenterally fed neonates to exceedingly high Mn concentrations in parenteral nutrition solutions, potentially increasing their risk for Mn-induced adverse health sequelae. The review will consider (1) the essentiality of Mn; (2) the concentration ranges, means and variation of Mn in various foods and infant formulas; (3) the absorption, distribution, and elimination of Mn after oral exposure and (4) the factors that raise a theoretical concern that neonates receiving total parenteral nutrition (TPN) are exposed to excessive dietary Mn.

The nematode Caenorhabditis elegans has emerged as an important animal model in various fields including neurobiology, developmental biology, and genetics. Characteristics of this animal model that have contributed to its success include its genetic manipulability, invariant and fully described developmental program, well-characterized genome, ease of maintenance, short and prolific life cycle, and small body size. These same features have led to an increasing use of C. elegans in toxicology, both for mechanistic studies and high-throughput screening approaches. We describe some of the research that has been carried out in the areas of neurotoxicology, genetic toxicology, and environmental toxicology, as well as high-throughput experiments with C. elegans including genome-wide screening for molecular targets of toxicity and rapid toxicity assessment for new chemicals. We argue for an increased role for C. elegans in complementing other model systems in toxicological research.

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