Advance Access publication August 6, 2008 Metabolomic Analyses of Body Fluids after Subchronic Manganese Inhalation in Rhesus Monkeys

Neurotoxicity is linked with high-dose manganese inhalation. There are few biomarkers that correlate with manganese exposure. Blood manganese concentrations depend upon the magnitude and duration of the manganese exposure and in-consistently reflect manganese exposure concentrations. The objective of this study was to search for novel biomarkers of manganese exposure in the urine and blood obtained from rhesus monkeys following subchronic manganese sulfate (MnSO4) in-halation. Liquid chromatography-mass spectrometry was used to identify putative biomarkers. Juvenile rhesus monkeys were exposed 5 days/week to airborne MnSO4 at 0, 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days or 1.5 mg Mn/m3 for 15 or 33 days. Monkeys exposed to MnSO4 at ‡ 0.06 mg Mn/m3 developed increased brain manganese concentrations. A total of 1097 parent peaks were identified in whole blood and 2462 peak