Biomarkers of Mn exposure in humans

Background: Studies have reported associations between manganese (Mn) exposures and Mn levels in blood and urine, though the suitability of these biological measures as biomarkers of exposure is not well known. Methods: We evaluated whether whole blood, plasma, and urine Mn levels reflect exposures in occupationally exposed humans. Results: In active ferroalloy workers, blood Mn was associated with total air Mn levels in subjects currently exposed to low (median = 0.42 μg/m³, P = 0.009) and moderate (median = 4.2 μg/m³, P = 0.007) air Mn levels, but not in workers exposed to the highest Mn levels (median = 292 μg/m³, P = 0.31). In bridge welders blood Mn (P < 0.01), but not plasma or urine Mn was significantly associated with their cumulative respiratory exposure index. In welders, ∼6% (range ∼3-9%) of whole blood Mn was contained in the plasma fraction, though there was no association between whole blood and plasma Mn levels (Pearson's R = 0.258, P = 0.12). In contrast, in fresh whole blood samples spiked with Mn ex vivo ∼80% or more of added Mn partitioned in the plasma, while only ∼20% or less partitioned in the cellular fraction. Conclusions: These data suggest a complex and limited relationship between exposure and blood Mn levels that may depend upon exposure attributes and the latency of blood sampling relative to exposure; plasma and urine Mn appear to be of little utility as exposure biomarkers. This underscores the need to fully characterize and validate these or other biomarkers for use in constructing appropriate exposure metrics and determining exposure-effect relationships.