NORA Manufacturing Sector Strategic Goals
927Z6RK - Effect of Stainless Steel Welding Fume Particulate on Lung Immunity in MiceStart Date: 10/1/2006
End Date: 9/30/2009
Principal Investigator (PI)Name: Stacey Anderson
Phone: 304-285-6174 X2
Funded By: NIOSH
Primary Goal Addressed5.0
Secondary Goal Addressed
Attributed to Manufacturing
There are an estimated 400,000 welders employed full-time in construction and manufacturing sectors. This project will evaluate the effect of occupational exposure to manual metal arc-stainless steel welding fumes (MMA-SS) on the immune system. Based on previous research and preliminary data, we propose that chronic welding fume exposure is immunosuppressive resulting in decreased antibody production. This project proposes to examine the antibody response after stainless steel welding fume exposure. After an alteration in antibody production can be confirmed, a potential mechanism of action by which the welding fumes are affecting the immune system will be determined through the analysis of cellular populations and cytokine levels.
An estimated 800,000 workers are employed full-time as welders worldwide and over 400,000 of these workers are estimated to be employed in the U.S as welders, cutters, solderers, and brazers. Still much larger numbers, believed to be more than one million, perform welding intermittently as part of their work duties. Arc welding is one of the most common forms of welding and includes the use of stainless steel electrodes which emit fumes containing chromium and nickel. Epidemological studies have identified large numbers of arc welders have experienced some type of adverse respiratory health effect. Alterations in the primary immune response of mice after chemical exposure is one of the best indicators of immunotoxicity. Previous work and preliminary data suggests that exposure to stainless steel welding fumes is immunosuppressive. This work proposes to evaluate the pulmonary immunotoxicity of stainless steel welding fumes. Humoral immunity will be evaluated in the murine mediastenial lymph nodes and broncoalveolar lavage fluid after pretreatment with welding fumes and challenge with antigen. IgM producing B-cells in the lymph nodes will be enumeration using the IgM plaque forming cell assay after challenge with sheep red blood cells and IgA, IgM and IgG levels will be enumerated in the bronchioalveloar lavage fluid using an enzyme linked immunosorbant assay (ELISA) after exposure to the human Pneumovax vaccine. If alterations in the primary antibody responses to antigen after pretreatment with welding fumes can be identifed, the individual components of the welding fume will be analyzed using the techniques described above to identify the immunotoxic portion. The effect of stainless steel welding fumes on occupational asthma will be investigated after sensitization with ovalbumin and pretreatment with welding fumes (Total and ovalbumin specific IgE). Cells participating in the immune response and their role with respect to immunosuppression will be characterized using a flourescence activated cell sorter and real-time polymerase chain reaction (PCR).
Studies investigating the health effects of welding fumes are limited. Previous research in animal models has demonstrated an increased susceptibility to infection after pretreatment with manual metal arc-stainless steel welding fumes (MMA-SS). In addition, we have preliminary data that also suggests exposure to stainless steel welding fumes is immunosuppressive. Based on these results, it is hypothesized that antibody levels stimulated by specific antigens will be decreased due to an inhibition of the function of the antigen presenting cells after welding fume exposure when compared to the vehicle controls. The overall goal of this proposal is to first characterize the effects, including cellular involvement and mechanism, of stainless steel welding fumes on pulmonary immunity and then identify the portion of the welding fume that is responsible for the immunomodulation.
This project will focus on the following specific aims:
• Analyze the alterations in mediastenial lymph node IgM antibody production in response to sheep red blood cells (SRBC) after pretreatment with MMA-SS, IgA, IgM and IgG production in the bronchoalveolar lavage fluid (BALF) in response to Pneumovax (Pvax) after pretreatment with MMA-SS, and serum IgE production in response to ovalbumin (OVA) after pretreatment with MMA-SS.
• Identify the key components of MMA-SS (specific metals, soluble/insoluble) that are responsible for antibody alterations in the lymph nodes and BALF.
• Begin to characterize the mechanisms behind the immune response to MMA-SS by identifying the cell populations that are involved and their specific cytokine profiles.
There are an estimated 400,000 workers employed full-time in the U.S as welders, cutters, solderers, and brazers and still larger numbers who perform welding intermittently as part of their work duties. Studies have identified up to 79% of welders to experience some type of adverse health effect. The most common adverse respiratory effects include; bronchitis, airway irritation, lung function changes, and increased susceptibility to infection. A possible increase in the incidence of lung cancer has also been suggested. Most epidemiological studies evaluating the health effects of welding are limited and inconclusive due to the large number of factors that influence exposure. At this point in time, animal studies examining the immunotoxic effects of welding fumes are even more limited. Our goal is to evaluate the hypothesis that exposure to stainless steel welding fumes is immunosuppressive. We plan to test our hypothesis by evaluating the primary immunological effects caused by welding fume exposure.
Results will address:
1) Construction (50%) Strategic Goal 6 (09PPCONSG6): Reduce welding fume exposures and future related health risks among construction workers by increasing the availability and use of welding fume controls and practices for welding tasks specifically Intermediate Goal 6.2 (09PPCONIG6.2) Increase awareness about welding fume hazards and known solutions among construction workers, contractors, owners, and suppliers; Research Goal 6.2.1 (09PPCONAOG6.2.1): Use communication science and best practices to develop welding fume hazard awareness materials. Develop materials in multiple languages and media to communicate exposure risks and availability of controls associated with welding fume; Intermediate Goal 6.5 (09PPCONIG6.5): Evaluate hazard and exposure assessment research gaps associated with welding fume in construction.
2) Manufacturing (50%) Strategic Goal 5 (09PPMNFSG5): Reduce the number of respiratory conditions and diseases due to exposures in the manufacturing sector from inhalation exposures to manufacturing materials.
Immune and Dermal (50%) Immune Strategic Goal 1 (09PPIMUSG1): Contribute to the reduction of immune abnormalities associated with workplace exposures, specifically Intermediate Goal 1.1 (09PPIMUIG1.1): Contribute to the advancement of knowledge regarding the impact of occupational exposures to chemicals or biological agents on normal immune function and Activity/output goal 1.1.3 (09PPIMUAOG1.1.3) Evaluate the immunotoxicity caused by exposure to certain occupational chemicals or allergen and Activity/output goal 1.1.4 (09PPIMUAOG1.1.4) Hazard identification of occupational chemicals/allergens. This project will also contribute to Dermal Strategic Goal 1(09PPDRMSG1): Contribute to the reduction of occupational skin disease specifically Activity/Output Goal 1.1.1 (09PPDRMAOG1.1.1) Identify incidence and prevalence of work-related dermatitis and characterize current work-related conditions and practices that impact the frequency and severity.
Respiratory Disease (50%) Strategic Goal 1 (09PPRDRSG1): Prevent and reduce work-related airways diseases specifically Intermediate Goal (09PPRDRIG1.1): prevent and reduce the full range of work-related asthma (WRA), including work-exacerbated asthma; occupational asthma; and irritant-induced asthma.
Exposure Assessment Emphasis area (100%) Strategic Goal 2 (09PPEXASG2): Develop or improve specific methods and tools to assess worker exposures to critical occupational agents and stressors specifically Intermediate Goal 2.4 (09PPEXAIG2.4): Develop biomonitoring methods including biomarkers that are useful for mixed exposures and Activity/Output 2.4.1 (09PPEXAAOG2.4.1): Development of new biomonitoring methods.
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