Archives of Toxicology

, Volume 84, Issue 7, pp 521–540 | Cite as

Dopaminergic neurotoxicity following pulmonary exposure to manganese-containing welding fumes

  • Krishnan SriramEmail author
  • Gary X. Lin
  • Amy M. Jefferson
  • Jenny R. Roberts
  • Rebecca S. Chapman
  • Bean T. Chen
  • Joleen M. Soukup
  • Andrew J. Ghio
  • James M. Antonini
Inorganic Compounds


The potential for development of Parkinson’s disease (PD)-like neurological dysfunction following occupational exposure to aerosolized welding fumes (WF) is an area of emerging concern. Welding consumables contain a complex mixture of metals, including iron (Fe) and manganese (Mn), which are known to be neurotoxic. To determine whether WF exposure poses a neurological risk particularly to the dopaminergic system, we treated Sprague–Dawley rats with WF particulates generated from two different welding processes, gas metal arc-mild steel (GMA-MS; low Mn, less water-soluble) and manual metal arc-hard surfacing (MMA-HS; high Mn, more water-soluble) welding. Following repeated intratracheal instillations (0.5 mg/rat, 1/week × 7 weeks) of GMA-MS or MMA-HS, elemental analysis and various molecular indices of neurotoxicity were measured at 1, 4, 35 or 105 days after last exposure. MMA-HS exposure, in particular, led to increased deposition of Mn in striatum and midbrain. Both fumes also caused loss of tyrosine hydroxylase (TH) protein in the striatum (~20%) and midbrain (~30%) by 1 day post-exposure. While the loss of TH following GMA-MS was transient, a sustained loss (34%) was observed in the midbrain 105 days after cessation of MMA-HS exposure. In addition, both fumes caused persistent down-regulation of dopamine D2 receptor (Drd2; 30–40%) and vesicular monoamine transporter 2 (Vmat2; 30–55%) mRNAs in the midbrain. WF exposure also modulated factors associated with synaptic transmission, oxidative stress, neuroinflammation and gliosis. Collectively, our findings demonstrate that repeated exposure to Mn-containing WF can cause persistent molecular alterations in dopaminergic targets. Whether such perturbations will lead to PD-like neuropathological manifestations remains to be elucidated.


Brain Dopaminergic dysfunction Manganese Neurotoxicity Neurodegeneration Occupational exposure Parkinson’s disease Parkinsonism Welding Welding fume 



Bronchoalveolar lavage fluid


Chemokine–chemokine ligand 2


Chemokine-X-chemokine ligand 2


Central nervous system




Divalent metal transporter 1


Dopamine D2 receptor


Egf-like module containing mucin-like hormone receptor-like 1


Fluorescence-linked immunosorbent assay


Glial fibrillary acidic protein


Gas metal arc-mild steel




Inductive coupled plasma atomic absorption spectroscopy


Interleukin 6


Integrin αM


Lactate dehydrogenase


Manual metal arc-hard surfacing


Nitric oxide synthase


Polymerase chain reaction


Parkinson’s disease


Polymorphonuclear leukocyte


Sodium dodecyl sulfate


Tyrosine hydroxylase


Tumor necrosis factor


Vesicular monoamine transporter 2


Welding fume


Conflict of interest statement

The authors declare they have no proprietary, financial or personal interest of any kind or nature in any samples, products, supplies, service or company that could be construed as being a conflict of interest.


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Copyright information

© US Government 2010

Authors and Affiliations

  • Krishnan Sriram
    • 1
    Email author
  • Gary X. Lin
    • 1
  • Amy M. Jefferson
    • 1
  • Jenny R. Roberts
    • 1
  • Rebecca S. Chapman
    • 1
  • Bean T. Chen
    • 1
  • Joleen M. Soukup
    • 2
  • Andrew J. Ghio
    • 2
  • James M. Antonini
    • 1
  1. 1.Health Effects Laboratory DivisionNational Institute For Occupational Safety and HealthMorgantownUSA
  2. 2.National Health and Environmental Effects Research LaboratoryUnited States Environmental Protection AgencyResearch Triangle ParkUSA

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