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Manufacturing

NORA Manufacturing Sector Strategic Goals

927Z6SA - Neurotoxicity After Pulmonary Exposure to Welding Fumes Containing Manganese

Start Date: 10/1/2006
End Date: 9/30/2010

Principal Investigator (PI)
Name: James Antonini
Phone: 304-285-6244
E-mail: jga6@cdc.gov
Organization: NIOSH
Sub-Unit: HELD
Funded By: NIOSH

Primary Goal Addressed
5.0

Secondary Goal Addressed
None


Attributed to Manufacturing
50%

Project Description

Short Summary

Millions of workers worldwide are exposed to welding aerosols daily. It has been suggested that welders are at an increased risk for the development of neurodegenerative diseases due to the presence of manganese in welding fume. Epidemiology studies regarding the neurological health of welders are inconclusive. An experimental model is needed that will examine the potential neurotoxic effects after inhalation to welding fume. A completely automated, computer-controlled welding fume generation and inhalation exposure system for laboratory animals has been developed. This project will assess the pulmonary and neurotoxic effects of animals exposed by inhalation to welding fumes that are composed of varying concentrations of manganese, supporting issues in respiratory diseases and Nanotechnology. Results will provide mechanistic information concerning welding fume exposure in the construction sector and be useful for risk assessment and the development of prevention strategies to protect exposed workers.



Description

Serious questions have been raised regarding a possible causal association between neurological effects in welders and the presence of manganese in welding consumables. Inhalation of pure manganese in high doses has been shown to cause neurological effects in exposed workers. However, manganese is not present as a pure element in welding fume. It is complexed with other metals and may not produce the same health effects as pure manganese. The most common electrodes used in welding (mild steel) are composed of mostly iron with small amounts of manganese, usually <5 % per total metal present. However, some hard-surfacing applications require welding electrodes that contain between 20-30 % manganese. The objective of the proposed study is to examine the potential neurotoxic and pneumotoxic effects of manganese in rats after pulmonary exposure to different welding fumes. Specific Aim (1) will determine the pulmonary and neurotoxic effects of animals exposed by inhalation to welding fumes that are composed of varying concentrations of manganese. Exposures will be to either a mild steel welding fume that contains a low level of manganese (<5 %) or a hard-surfacing welding fume that contains a high level of manganese (~30 %). Animals will be exposed to a welding fume concentration of 15 mg/m3 for 3 hours/day for 5 days/week for 10 weeks. Pulmonary responses will be examined by standard lung histopathology methods and measuring lung injury and inflammation parameters in lung fluid collected from exposed animals. Neurotoxicity will be detected and quantified in discrete brain regions by measuring the increased expression of glial fibrillary acidic protein (GFAP) and using silver degeneration staining technology. Because dopaminergic systems have been implicated as targets of manganese exposure, levels of dopamine and tyrosine hydroxylase, biomarkers of dopaminergic neuronal damage, will be measured. Specific Aim (2) will determine the manganese content in the blood, lungs, and specific brain regions of animals exposed by inhalation to welding fumes that are composed of varying concentrations of manganese. In addition, welding particle deposition will be examined in sections of upper and lower airways of exposed animals in an attempt to determine the potential mechanisms by which manganese in welding fumes may access the central nervous system (e.g., olfactory transport vs. systemic delivery). Specific Aim (3) will compare the neurotoxic effects and brain, blood, and lung concentrations of manganese after intratracheal instillation of mild steel or hard-surfacing welding fumes with the same effects observed after intratracheal instillation of insoluble or soluble forms of pure manganese. This aim will assess the fate and bioavailability of manganese that is complexed with other metals in welding fume after direct delivery to the lungs. The results of this investigation will be collated into a NIOSH project database and will provide important information concerning the neurotoxic effects of welding fume exposure. Detailed descriptions of the methodologies and results from the study will be published in peer-reviewed journals and presented at international scientific conferences in the fields of toxicology, occupational and environmental health, aerosol science and technology, and respiratory health. Results will be shared with welding trade associations. Welding is a common process in the manufacturing and construction sectors. Welding issues have been listed as a critical item by the manufacturing and construction sector workgroups.



Objectives

Millions of workers worldwide are exposed to welding aerosols daily. Nearly 350,000 workers are classified as full-time welders in the United States. It has been suggested that welders are at an increased risk for the development of neurodegenerative diseases due to the presence of manganese in welding fumes. Epidemiology studies regarding the neurological health of welders are inconclusive. An experimental model is needed that could examine the potential neurotoxic effect of manganese after pulmonary exposure to welding fume. A completely automated, computer-controlled welding fume generation and inhalation exposure system for laboratory animals has been developed by NIOSH. Detailed descriptions of the methodologies and results from the study will be published in peer-reviewed journals and presented at international scientific conferences in the fields of toxicology, occupational and environmental health, aerosol science and technology, and respiratory health. Results will be shared with welding trade associations. The objectives of the project are: (1) To determine the pulmonary and neurotoxic effects of animals exposed by inhalation to welding fumes that are composed of varying concentrations of manganese; (2) To determine the manganese content in the blood, lungs, and specific brain regions of animals exposed by inhalation to welding fumes that are composed of varying concentrations of manganese; (3) To compare the neurotoxic effects and brain, blood, and lung concentrations of manganese after intratracheal instillation of welding fumes composed of varying concentrations of manganese with the same effects observed after intratracheal instillation of insoluble or soluble forms of pure manganese.



Mission Relevance

Millions of workers worldwide are exposed to welding aerosols daily. Nearly 350,000 workers are classified as full-time welders in the United States. However, it is believed that significantly greater numbers of workers perform welding duties, but are not classified as full-time welders. Numerous studies have evaluated the health effects associated with exposures during welding. A large majority of these studies have focused on the respiratory effects of welding fume. Bronchitis, metal fume fever, siderosis, and cancer have all been reported in welders. Less information exists regarding the non-pulmonary effects associated with welding, specifically the potential neurological effects. It has been suggested that welders are at an increased risk for the development of neurodegenerative diseases due to the presence of manganese in welding fumes. However, epidemiology studies regarding the neurological health of welders are inconsistent. The health effects of welders can be difficult to study because of variations in workplace setting and exposure to complex aerosol mixtures generated from different processes. Welders may work in a number of settings that include open, well-ventilated spaces (e.g., outdoors on a construction site) or confined, poorly-ventilated spaces (e.g., ship hull, building crawl space, pipeline). Arc welding processes can be quite complex. There are at least 80 different types- each with its own potential safety and health hazard. An experimental model is needed that will examine the potential neurotoxic effect of manganese after inhalation to a tightly-controlled welding fume exposure. The Health Effects Laboratory Division in NIOSH has developed a completely automated, computer-controlled welding fume generation and inhalation exposure system for laboratory animals. Preliminary fume characterization studies have indicated that particle morphology, size, and chemical composition are comparable to welding fume generated in the workplace. Standard biochemical and histopathological analyses will be carried out on exposed animals to assess the potential neurological responses associated with welding fume inhalation. With the development of this novel system, an animal model has been established using controlled welding exposures to investigate the possible mechanisms by which welding fume may affect the pulmonary and central nervous systems. Results of this project will be presented at scientific conferences, published in peer-reviewed journals, and shared with welding trade associations. Data are likely to influence work practices and prevention strategies.


Research results will address the following goals: 1) Construction Sector (50%): 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. Intermediate Goal 6.5 (09PPCONIG6.5) – Evaluate hazard and exposure assessment gaps associated with welding fumes in construction. Research Goal 6.5.1 (09PPCONAOG6.5.1) Health hazard testing component. 2) Manufacturing Sector (50%): 09PPMNFSG5- Reduce the number of respiratory conditions and diseases due to exposures in the Manufacturing Sector. 3) Respiratory Disease Cross-Sector Health Outcome (50%): 09PPRDRSG1- Prevent and reduce work-related airways diseases; Intermediate Goal 1.2 (09PPRDRIG1.2)- Prevent and reduce COPD; 09RDRSG5- Prevent respiratory and other diseases potentially resulting from occupational exposures to nanomaterials. Strategic Goal 3 (09PPRDRSG3): Prevent and reduce work-related respiratory infectious diseases.; Activity/Output Goal (09PPRDRAOG3.2.1): evaluate the impact of occupational exposures on susceptibility to respiratory infection, including underlying mechanisms. Occupational exposures of current concern include welding fume and its constituents; diesel exhaust; residual oil fly ash (ROFA); silica; and potentially others, if evidence suggests that exposure increases risk of respiratory infection. 4) Cancer, Reproductive, and Cardiovascular Diseases Cross-Sector Health Outcome (50%): 09PPCRCSG5- Reduce the incidence and mortality of other chronic diseases, including (but not limited to), work-related neurologic (cerebrovascular) and renal disease. 5) Other Cross-Sector Programs, Nanotechnology (50%): 09PPNANSG1- Determine if nanoparticles and nanomaterials pose risks of work-related injuries and illnesses. Intermediate Goal 2 (09PPNANIG2)- Toxicity and Internal dose.



Page last updated: June 3, 2011
Page last reviewed: May 23, 2011
Content Source: National Institute for Occupational Safety and Health (NIOSH) Office of the Director

 

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