Millions of workers, including over 500,000 welders employed in the United States, have been exposed to excessive metals. Human and animal studies have strongly linked metal exposure to neurophysiological disorders and neurodegenerative diseases. Manganese (Mn) is one of the most significant metal neuro- toxicants among workers. Many occupational studies have documented Mn toxicity. However, the threshold of Mn exposure, the mechanism of the toxicity of Mn, and the interaction of Mn with other metals (such as lead and mercury) are unknown and therefore deserve further investigation. One pending issue in assessment of Mn exposure pertains to the selection of proper biomarker. Over 40% of Mn in human body is stored in bone, which renders bone Mn to be the ideal biomarkers to assess cumulative Mn in the body with long-term, low dose exposure, a pattern typically seen among workers occupationally exposed to Mn. In this project, a novel neutron activation analysis technology will be developed to noninvasively quantify Mn in bone in vivo. Later we will apply this technology in a larger project to study the possible synergistic neurotoxic effect of the exposure of metal mixtures among worker populations. Our central hypothesis to be tested in this proposal is that a novel transportable neutron activation analysis technology can be developed and validated for non invasive in vivo quantification of Mn in bone. We will conduct a series of Monte Carlo simulations to select the best design of the system, set up the system based on the chosen design, optimize the design with experiments, and develop new algorithms to analyze the data and calibrate the system. At the completion of this project, a novel technology for cumulative Mn exposure assessment will be established. The new technology and knowledge will help to fill the data gaps regarding appropriate individual exposure assessment of metals and to provide valuable information on early diagnose of Mn exposure and toxicity. The use of new biomarker to understand the neurotoxic effects of exposure to Mn is critical to millions of workers who have been exposed to Mn for two main reasons. First, neurophysiological disorder is one of the main health issues for these workers;second, neurological impairment reduces the workers'productivity and is a major cause for work related injuries. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

Public Health Relevance

The proposed research is relevant to occupation health because it addresses a critical problem regarding the development and validation of a novel technology to assess cumulative exposure to one of the most significant metal neuro-toxicants, manganese, among workers. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

Agency
National Institute of Health (NIH)
Institute
National Institute for Occupational Safety and Health (NIOSH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21OH010044-01A2
Application #
8303563
Study Section
Safety and Occupational Health Study Section (SOH)
Program Officer
Frederick, Linda J
Project Start
2012-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$232,175
Indirect Cost
$32,175
Name
Purdue University
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Specht, Aaron J; Parish, Chris N; Wallens, Emma K et al. (2018) Feasibility of a portable X-ray fluorescence device for bone lead measurements of condor bones. Sci Total Environ 615:398-403
Specht, Aaron J; Weisskopf, Marc G; Nie, Linda Huiling (2017) Theoretical modeling of a portable x-ray tube based KXRF system to measure lead in bone. Physiol Meas 38:575-585
Liu, Yingzi; Mostafaei, Farshad; Sowers, Daniel et al. (2017) Customized compact neutron activation analysis system to quantify manganese (Mn) in bone in vivo. Physiol Meas 38:452-465
Specht, Aaron J; Mostafaei, Farshad; Lin, Yanfen et al. (2017) Measurements of Strontium Levels in Human Bone In Vivo Using Portable X-ray Fluorescence (XRF). Appl Spectrosc 71:1962-1968
Byrne, Patrick; Mostafaei, Farshad; Liu, Yingzi et al. (2016) The study of in vivo quantification of aluminum (Al) in human bone with a compact DD generator-based neutron activation analysis (NAA) system. Physiol Meas 37:649-60
Specht, Aaron J; Lin, Yanfen; Weisskopf, Marc et al. (2016) XRF-measured bone lead (Pb) as a biomarker for Pb exposure and toxicity among children diagnosed with Pb poisoning. Biomarkers 21:347-52
Sowers, Daniel; Liu, Yingzi; Mostafaei, Farshad et al. (2015) A Dosimetry Study of Deuterium-Deuterium Neutron Generator-based In Vivo Neutron Activation Analysis. Health Phys 109:566-72
Mostafaei, Farshad; Blake, Scott P; Liu, Yingzi et al. (2015) Compact DD generator-based neutron activation analysis (NAA) system to determine fluorine in human bone in vivo: a feasibility study. Physiol Meas 36:2057-67
O'Neal, Stefanie L; Hong, Lan; Fu, Sherleen et al. (2014) Manganese accumulation in bone following chronic exposure in rats: steady-state concentration and half-life in bone. Toxicol Lett 229:93-100
Liu, Yingzi; Byrne, Patrick; Wang, Haoyu et al. (2014) A compact DD neutron generator-based NAA system to quantify manganese (Mn) in bone in vivo. Physiol Meas 35:1899-911

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