Characterization of Functional and Molecular Endpoints of Potential Adverse Health Effects Associated with Age, Diet, and Occupational Exposure in an Animal Model
Public Domain
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2018/03/01
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Details
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Personal Author:Antonini JM ; Cumpston JB ; Cumpston JL ; Erdely A ; Kashon M ; Kodali VK ; Leonard HD ; McKinney W ; Meighan T ; Roach KA ; Roberts, Jennifer R. ; Salmen R ; Shoeb M ; Stone S ; Zeidler-Erdely P
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Description:The exposome is the measure of all exposures of an individual in a lifetime from conception to death and how those exposures affect health. An individual's exposome is highly variable and dynamic throughout their lifetime. The goal was to design an exposure paradigm that would address multiple exposome components, including lifestyle (e.g., diet), age, and occupational exposure (welding fume; WF) in a controlled animal model. Functional and molecular endpoints predictive of adverse health effects in recovered biological fluids of exposed animals that are translatable to human populations were examined. Male Fischer 344 rats were maintained on a high fat western (HF) or regular (REG) diet for 24 wk. At wk 7 during diet maintenance, groups of rats were exposed by inhalation of stainless steel WF (20 mg/m3 x 3 hr/d x 4 d/wk x 5 wk) or filtered air (control) until wk 12 at which time some animals were euthanized. A separate set of rats were allowed to recover from WF exposure until the end of the 24 wk period. Whole blood and bronchoalveolar lavage fluid were collected at 7 wk (baseline before WF exposure), 12, and 24 wk to assess blood cell differential and to recover serum, peripheral blood mononuclear cells (PBMCs), and lung phagocytes for epigenetic analysis and immune response. Significantly elevated % change in body weight and serum triglycerides were observed in groups maintained on the HF diet. At nearly all time points, phagocytosis of bacteria by recovered phagocytes and PBMC telomere length were significantly decreased in the REG+WF, HF+air, and HF+WF groups compared to the REG+air group. A significant decrease also was observed in telomere length over the 24 wk regimen in all groups. In summary, age, diet, and occupational exposure (WF inhalation), important exposome components, altered immune response and epigenetic endpoints in rats. An animal model may be advantageous for studying the exposome because of the ability to control all external exposures and to measure potential adverse health outcomes of each animal over its entire lifespan and to link a specific internal biological response/endpoint with a specific exposure. [Description provided by NIOSH]
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ISSN:1096-6080
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Volume:162
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Issue:1
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NIOSHTIC Number:nn:20051186
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Citation:Toxicologist 2018 Mar; 162(1):216
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Federal Fiscal Year:2018
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Peer Reviewed:False
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Source Full Name:The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
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Main Document Checksum:urn:sha-512:3ebac2af8b0cbe4a41b638b94e2da6d0a617a750ee52c99f98558d8025e9b331c81e46129632439f7d19488054a27cb21ccadc959ed01212bb8755c642325f67
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