Tooth manganese as a biomarker of exposure and body burden in rats

Background: Neonates and children are particularly vulnerable to the toxic effects of excess manganese (Mn), but studies of Mn exposure during these developmental periods are hampered by a lack of validated biomarkers. Deciduous teeth may be used to assess Mn exposure during these developmental periods but require further validation to determine the relationship between tooth Mn, Mn in target tissues, and exposure. Objectives: To determine the relationship of tooth Mn concentrations with: (i) exposure dose, (ii) the timing/duration of exposure, and (iii) with Mn concentrations in blood, brain and bone. Methods: Rats in different treatment groups were orally exposed to 0, 25 or 50 mu g/g/day Mn either from postnatal day (PND) 1 - 21 and culled at PND 24, from PND 1 - 21 and culled as adults (> PND 290), or from PND 1 throughout life and culled at > 290 PND. Mn was measured in second molars, femurs, brain and blood by ICP-MS. Results: Tooth Mn increased significantly with dose in rats exposed for 21 PND and culled at 24 PND (p < 0.001). In rats culled at > 290 PND, tooth Mn increased with exposure duration (p < 0.001) and reflected exposure duration. A significant, positive association between tooth Mn and Mn levels in blood (Spearman's rho 0.69, p < 0.01) brain (rho 0.59, p < 0.05) and bone (rho 0.69, p < 0.01) was observed in animals with lifelong exposure. Tooth Mn and Mn levels in bone were also significantly positively associated in animals exposed only early in life (rho 0.76, p < 0.001). Conclusions: Teeth are a sensitive biomarker of active and past Mn exposure and Mn burden in tissues. Unlike blood, teeth retain information on exposure history over the short and long-term.