Alice Hamilton Awards: Research Updates for 2011 - Biological Sciences

This study demonstrated that repeated pulmonary exposure to manganese-containing welding fumes caused mitochondrial dysfunction and altered the expression of specific Parkinson's disease-linked (Park) genes, which are familial mutations associated with early onset forms of the disease. These findings may address the emerging concern that workplace exposure to welding fumes may accelerate the onset of Parkinsonism and may provide clues to the pathogenesis of the disease. Further, as the loss of these Park proteins preceded any observable neurobehavioral or neuropathological abnormalities, their utility as early biomarkers of welding fume-related neurotoxicity is promising. Also, such injury markers will be useful in identifying susceptible worker populations at risk of adverse welding fume exposures.

Since receiving the 2011 Alice Hamilton Award for Biological Sciences, several updates have occurred regarding welding fume-related neurotoxicity studies conducted by the research team led by Dr. Sriram (Health Effects Laboratory Division):

• Press coverage:The findings from the winning article were highlighted in the "Science News" magazine's feature article entitled "Destination Brain: Inhaled pollutants may inflame more than the lungs" published on May 22, 2010; Vol.177 #11 (p. 16) and in a feature article entitled "Dirty Minds" published by the Australian Science Magazine "COSMOS", Issue 37, March 2011 (http://www.cosmosmagazine.com/features/print/4268/dirty-minds).

• Nomination for CDC Science Award: The winning article was nominated by NIOSH for the 2011 CDC Charles Shepard Science Award under the Laboratory Methods category.

• Research Update: We have recently demonstrated that manganese levels in nail clippings of rats repeatedly exposed to welding fumes strongly correlated with manganese accumulation in dopaminergic brain areas, striatum and midbrain. Further, we showed that brain manganese at concentrations similar to that seen in nail clippings was able to elicit dopaminergic abnormality, including loss of specific Park proteins. Particularly, a significant correlation between nail manganese accumulation and loss of striatal Park7 protein was demonstrated. These findings suggest that nail manganese has the potential to be a sensitive and reliable biomarker for welding fume-related manganese 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 welding fume exposures in occupational settings. This work was recently published in the journal Toxicology (doi:10.1016/j.tox.2011.10.021).

Another exciting observation is that modulating welding process conditions can influence the fume composition and neurotoxicological potential of manganese-containing welding fumes. Specifically, we observed that by increasing welding voltage, keeping current and shielding gas constant, the manganese component in welding fumes was less soluble and consequently less toxic. More importantly, such modifications to welding process conditions did not compromise the quality of the weld. A manuscript describing these findings is in preparation. Our findings show promise as a potential prevention strategy for manganese exposure during welding that can have a significant impact in revising welding protocols implemented at the workplace, thereby reducing adverse exposures.

Future plans include whole-body inhalation studies in experimental animals to mimic human exposure conditions to welding fumes. Animals will be exposed to welding fumes at aerosol mass concentrations comparable to that generated at the workplace and within the cumulative exposure limits that a welder may experience over a period of several years in the profession. The welding electrodes proposed for investigation include, Gas metal Arc (GMA)-mild steel (GMA-MS) and GMA-stainless steel (GMA-SS), since GMA welding is the most prevalent type of welding process used in the industry. These electrodes were selected on the basis of their metal composition (particularly the composition of manganese, which is suspected to be the neurotoxic component in welding fumes), as well as, solubility of the metal components, a factor that may influence translocation of metals from the olfactory or pulmonary regions to the brain.

To summarize, three important findings have emerged from ongoing neurotoxicity studies conducted with the welding fumes. First, our findings of the involvement of Park genes in the neurotoxicity of welding fumes means that they need to be assessed as potential neurotoxicity biomarkers for adverse welding fume exposures. Second, our findings that accumulation of manganese in nails selectively reflects the pattern of manganese accumulation in the brain and exhibits a strong correlation with dopaminergic injury markers, suggests that the nail can serve as a reliable surrogate to monitor welding fume-related manganese exposure and associated neurotoxicity. Third, our findings on the lack of neurotoxicity of welding fumes when process conditions, such as the welding voltage used, are altered, suggest that simple modifications of processes may alter the fume profile and reduce its neurotoxic potential. Because welding process conditions can be easily controlled at the workplace, such efforts may contribute to the prevention of adverse exposures and associated neurological risks.