Mild steel welding fume causes manganese accumulation and subtle neuroinflammatory changes but not overt neuronal damage in discrete brain regions of rats after short-term inhalation exposure.
Serious questions have been raised by occupational health investigators regarding a possible causal association between neurological effects in welders and the presence of manganese (Mn) in welding fume. Male Sprague-Dawley rats were exposed by inhalation to 40 mg/m(3) of gas metal arc-mild steel (MS) welding fume for 3 h/day for 10 days. Generated fume was collected in the animal chamber during exposure, and particle size, composition, and morphology were characterized. At 1 day after the last exposure, metal deposition in different organ systems and neurological responses in dopaminergic brain regions were assessed in exposed animals. The welding particles were composed primarily of a complex of iron (Fe) and Mn and were arranged as chain-like aggregates with a significant number of particles in the nanometer size range. Mn was observed to translocate from the lungs to the kidney and specific brain regions (olfactory bulb, cortex, and cerebellum) after MS fume inhalation. In terms of neurological responses, short-term MS fume inhalation induced significant elevations in divalent metal ion transporter 1 (Dmt1) expression in striatum and midbrain and significant increases in expression of proinflammatory chemokines (Ccl2, Cxcl2) and cytokines (IL1beta, TNFalpha) in striatum. In addition, mRNA and protein expression of glial fibrillary acidic protein (GFAP) was significantly increased in striatum after MS fume exposure. However, the 10-day MS welding fume inhalation did not cause any changes in dopamine and its metabolites or GABA in dopaminergic brain regions nor did it produce overt neural cell damage as assessed by histopathology. In summary, short-term MS welding fume exposure led to translocation of Mn to specific brain regions and induced subtle changes in cell markers of neuroinflammatory and astrogliosis. The neurofunctional significance of these findings currently is being investigated in longer, more chronic welding fume exposure studies.
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. jga6@cdc.gov
James M
JM
Antonini
Krishnan
K
Sriram
Stanley A
SA
Benkovic
Jenny R
JR
Roberts
Samuel
S
Stone
Bean T
BT
Chen
Diane
D
Schwegler-Berry
Amy M
AM
Jefferson
Brenda K
BK
Billig
Christopher M
CM
Felton
Mary Ann
MA
Hammer
Fang
F
Ma
David G
DG
Frazer
James P
JP
O'Callaghan
Diane B
DB
Miller
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry / Q000379:methods; D004660:Encephalitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000737:chemistry; D008297:Male; D008345:Manganese / Q000378:metabolism*; D009930:Organic Chemicals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013232:Steel / Q000633:toxicity*; D014896:Welding; D000099236:Solute Carrier Family 11, Member 2
D002395:Catecholamines; D027682:Cation Transport Proteins; D016207:Cytokines; D004298:Dopamine; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D006719:Homovanillic Acid; D008345:Manganese; D009930:Organic Chemicals; D013232:Steel; D000099236:Solute Carrier Family 11, Member 2; C435731:fluoro jade