Dopaminergic Neurotoxicity Following Pulmonary Exposure to Manganese-Containing Welding Fumes

Details

• Personal Author:
  Antonini JM ; Chapman RS ; Chen BT ; Ghio AJ ; Jefferson AM ; Lin GX ; Roberts, Jennifer R. ; Soukup JM ; Sriram K
• Description:
  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 9 7 weeks) of GMA-MS or MMAHS, 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. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Chemistry Environmental Monitoring Hazardous Substances Hypersensitivity Laboratories Manganese Nervous System Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety Welding Workplace

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• Keywords:
  Author Keywords: Brain Biological-effects Chemical-hypersensitivity Chemical-properties Dopaminergic Dysfunction Exposure-assessment Exposure-levels Exposure-methods Fumes Inhalation-studies Laboratory-animals Laboratory-testing Nerve-function Neurodegeneration Neurological-system Neurotoxic-effects Neurotoxicity Occupational-exposure Occupational Exposure Parkinsonism Parkinsons Disease Physiological-factors Physiological-testing Pulmonary-system-disorders Respiratory-gas-analysis Respiratory-system-disorders Statistical-analysis Toxic-effects Welders Welders-lung Work-environment Work-operations Work-practices

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• ISSN:
  0340-5761
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  84
• Issue:
  7
• NIOSHTIC Number:
  nn:20036562
• Citation:
  Arch Toxicol 2010 Jul; 84(7):521-540
• Contact Point Address:
  Krishnan Sriram, Health Effects Laboratory Division, National Institute For Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  kos4@cdc.gov
• CAS Registry Number:
  L-Tyrosine (CAS RN 55520-40-6)
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Archives of Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c1e69ff5f90362b3438daf6a9a6c504979487bbc959aa341822054e9c26110290e3728d45d65c2457a42bed78bbdd8fd0b1dd19297e5c1affc20f32fe4738fa5
• Download URL:
  https://stacks.cdc.gov/view/cdc/187930/cdc_187930_DS1.pdf
• File Type:
  [PDF - 584.02 KB ]