Biokinetically-based in vitro cardiotoxicity of residual oil fly ash: hazard identification and mechanisms of injury

Details

• Personal Author:
  Dreher KL ; Jaskot R ; Knuckles TL ; Ledbetter A ; Linak WP ; McGee J ; Miller CA ; Richards JH
• Description:
  Epidemiological studies have associated air pollution particulate matter (PM) exposure with adverse cardiovascular effects. Identification of causal PM sources is critically needed to support regulatory decisions to protect public health. This research examines the in vitro cardiotoxicity of bioavailable constituents of residual oil fly ash (ROFA) employing in vivo, biokinetically-based, concentrations determined from their pulmonary deposition. Pulmonary deposition of ROFA led to a rapid increase in plasma vanadium (V) levels that were prolonged in hypertensive animals without systemic inflammation. ROFA cardiotoxicity was evaluated using neonatal rat cardiomyocyte (RCM) cultures exposed to particle-free leachates of ROFA (ROFA-L) at levels present in exposed rat plasma. Cardiotoxicity was observed at low levels (3.13 ug/mL) of ROFA-L 24 h post-exposure. Dimethylthiourea (28 mM) inhibited ROFA-L-induced cytotoxicity at high (25-12.5 ug/mL) doses, suggesting that oxidative stress is responsible at high ROFA-L doses. Cardiotoxicity could not be reproduced using a V + Ni + Fe mixture or a ROFA-L depleted of these metals, suggesting that ROFA-L cardiotoxicity requires the full complement of bioavailable constituents. Susceptibility of RCMs to ROFA-L-induced cytotoxicity was increased following tyrosine phosphorylation inhibition, suggesting that phosphotyrosine signaling pathways play a critical role in regulating ROFA-L-induced cardiotoxicity. These data demonstrate that bioavailable constituents of ROFA are capable of direct adverse cardiac effects. [Description provided by NIOSH]
• Subjects:
  Air Pollution Animals Cardiovascular Diseases Cardiovascular System Environmental Exposure Epidemiology Hazardous Substances Laboratories Lung Lung Diseases Metals Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Air Pollution Author Keywords: ROFA Biokinetics Cardiac Function Cardiac Injury Cardiac Toxicity Cardiovascular System Disease Cardiovascular System Disorders Exposure Levels Hypertension In Vitro Study In Vivo Study Laboratory Animals Metal Compounds Metallic Compounds Oxidative Stress Particulates PM Pulmonary Effects Pulmonary System Disorders Risk Factors Toxic Effects Toxins

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• ISSN:
  1530-7905
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  426-437
• Volume:
  13
• Issue:
  4
• NIOSHTIC Number:
  nn:20049368
• Citation:
  Cardiovasc Toxicol 2013 Dec; 13(4):426-437
• Contact Point Address:
  K. L.Dreher, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Mail Drop B105-02, 109 TW Alexander Drive, Research Triangle Park, NC 27711
• Email:
  Dreher.Kevin@epa.gov
• Federal Fiscal Year:
  2014
• Performing Organization:
  West Virginia University
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Cardiovascular Toxicology
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d701b3b3852e269f94c0a5985b4b5df6eb8f080fa5271c333c7fa53b6f08edcf676258a24acec34e1b82a6f50e0a03ef9d2448cf03dc7fff6319d4a5dcafa03c
• Download URL:
  https://stacks.cdc.gov/view/cdc/203832/cdc_203832_DS1.pdf
• File Type:
  [PDF - 502.17 KB ]