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Dopaminergic neurotoxicity following exposure to manganese-containing welding fumes.
Toxicologist 2010 Mar; 114(1):5
The potential for development of Parkinson's disease (PD)-like neurological dysfunction following occupational exposure to welding fumes (WF) is an area of emerging concern. Welding generates a complex aerosol of fine and ultrafine metal particles that can potentially translocate from olfactory or pulmonary targets and accumulate in the brain. Manganese (Mn) in welding consumables is thought to be the causative factor for development of neurological deficits seen in welders. However, lack of definitive epidemiological evidence for such a causal association warrants further experimental investigation. To address this, Sprague-Dawley rats were exposed by whole-body inhalation or intra-tracheal instillation to a variety of WFs that differ in elemental composition and solubility. Short-term inhalation exposure (40mg/m3; 3h/d x 10d) to gas metal arc-mild steel (GMA-MS; low Mn, less soluble) resulted in deposition of Mn in the olfactory bulb and striatum, altered the expression of divalent metal transporter 1 (Dmt1), dopamine D1 (Drd1) and D2 (Drd2) receptors, and induced a subtle neuroinflammatory response in the striatum and midbrain. On the other hand, a similar exposure to gas metal arc-stainless steel (GMA-SS; high chromium, less soluble) did not affect any of the indices described above. Repeated intratracheal instillations (0.5mg/rat, 1/week x 7 weeks) of GMAMS or manual metal arc-hard surfacing (MMA-HS; high Mn, more soluble) also led to deposition of Mn in the brain. By 1d post-exposure, both fumes caused loss of tyrosine hydroxylase (TH) protein and altered the expression of various synaptic proteins in the striatum and midbrain. While loss of TH following GMA-MS was transient, a sustained loss was observed in the midbrain even after cessation of MMA-HS exposure. In addition, both fumes down-regulated Drd1, Drd2 and Vmat2 mRNAs in the midbrain. Whether such effects will persist and cause neurodegeneration remains to be elucidated. Current research aims at addressing these concerns, which may help support or refute findings that suggest an association between WF exposure and PD-like neurological disorder.
Biological-effects; Cell-biology; Chemical-hypersensitivity; Epidemiology; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Laboratory-animals; Laboratory-testing; Nervous-system-disorders; Neuromotor-disorders; Particle-aerodynamics; Particulates; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Welding
Issue of Publication
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah