title: Manganese accumulation in nail clippings as a biomarker of welding fume exposure and neurotoxicity.
abstract: Occupational exposure to welding fumes (WF) is thought to cause Parkinson's disease (PD)-like neurological dysfunction. An apprehension that WF may accelerate the onset of PD also exists. Identifying reliable biomarkers of exposure and neurotoxicity are therefore critical for biomonitoring and neurological risk characterization of WF exposure. Manganese (Mn) in welding consumables is considered the causative factor for the neurological deficits seen in welders. Hence, we sought to determine if Mn accumulation in blood or nail clippings can be a marker for adverse exposure and neurotoxicity. To model this, rats were exposed by intratracheal instillation to dissolved or suspended fume components collected from gas metal arc-mild steel (GMA-MS) or manual metal arc-hard surfacing (MMA-HS) welding. Trace element analysis revealed selective Mn accumulation in dopaminergic brain areas, striatum (STR) and midbrain (MB), following exposure to the two fumes. This caused dopaminergic abnormality as evidenced by loss of striatal tyrosine hydroxylase (Th; 25-32% decrease) and Parkinson disease (autosomal recessive, early onset) 7 (Park7; 25-46% decrease) proteins. While blood Mn was not detectable, Mn levels in nails strongly correlated with the pattern of Mn accumulation in the striatum (R(2)=0.9386) and midbrain (R(2)=0.9332). Exposure to manganese chloride (MnCl(2)) caused similar Mn accumulation in STR, MB and nail. Our findings suggest that nail Mn has the potential to be a sensitive and reliable biomarker for long-term Mn exposure and associated neurotoxicity. The non-invasive means by which nail clippings can be collected, stored, and transported with relative ease, make it an attractive surrogate for biomonitoring WF exposures in occupational settings.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA. kos4@cdc.gov
authors.forename: Krishnan
authors.initials: K
authors.lastname: Sriram
authors.forename: Gary X
authors.initials: GX
authors.lastname: Lin
authors.forename: Amy M
authors.initials: AM
authors.lastname: Jefferson
authors.forename: Jenny R
authors.initials: JR
authors.lastname: Roberts
authors.forename: Ronnee N
authors.initials: RN
authors.lastname: Andrews
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
mesh_terms: D000395:Air Pollutants, Occupational / Q000009:adverse effects* / Q000633:toxicity*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D004784:Environmental Monitoring / Q000379:methods; D006724:Hoof and Claw / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects* / Q000032:analysis*; D008168:Lung / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000009:adverse effects* / Q000378:metabolism* / Q000493:pharmacokinetics; D020149:Manganese Poisoning / Q000378:metabolism*; D008670:Metals / Q000032:analysis / Q000493:pharmacokinetics; D009262:Nails / Q000737:chemistry* / Q000378:metabolism*; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014896:Welding
chemical_list: D000395:Air Pollutants, Occupational; D015415:Biomarkers; D008670:Metals; D008345:Manganese; D004298:Dopamine