Significance and Usefulness of Biomarkers of Exposure to Manganese

Abstract

Manganese (Mn) accomplishes functions essential to maintaining human health, but at the same time this trace element can be toxic at low levels of exposure and accurate estimation of internal exposure is needed. A biomarker of exposure to Mn is meaningful only if there is sufficient knowledge of the toxicokinetics determining its presence in a biological medium (e.g. whole blood, plasma, urine, hair, nail). Moreover, biological monitoring of exposure to Mn is useful only when the biomarker is sufficiently specific and sensitive to distinguish exposed from non-exposed subjects, when it is dose-related to the external exposure (current, recent, or time-integrated), and when it displays reasonable dose–effect/response relationships with the occurrence of adverse effects on the central nervous system, the critical target for Mn exposure. Human investigations in which biomarkers of Mn exposure meet all these criteria are hard to locate. Overall, the available studies report poor or no associations on an individual basis between external (Mn in air or drinking water) and internal (Mn in blood, urine, hair, or nail) Mn exposure indices. This may be to some extent explained by features inherent of the Mn metabolism (homeostatic control), the Mn biomarker's half-life with respect to the exposure window, and the variable nature of external exposure scenarios. Studies particularly dealing with Mn inhalation exposure, different or poorly described methodological approaches, or air sampling strategies may render direct comparison and interpretation of results a tedious task. Nevertheless, several studies report significant dose–effect associations between biomarkers of Mn exposure and subclinical deficits of psychomotor or neuropsychological test performances. Because directly associated with the site of toxic action and providing the magnetic resonance imaging is done no later than three months after Mn exposure ceased, the Mn T1 relaxation time is potentially the better biomarker of Mn exposure in a clinical context (e.g. after long-term parenteral nutrition, chronic liver failure, methcathinone drug abuse). Magnetic resonance imaging is, however, unpractical as a tool for biological monitoring of exposure to Mn in the occupational setting (inhalation) and in the general population (air, drinking water). In conclusion, it would be inappropriate to recommend, on the basis of the currently available evidence, a reliable well-validated biomarker of exposure to Mn, or to establish a health-based threshold value for subclinical neurotoxic effects.