EPA Science Inventory

Biokinetically-Based In Vitro Cardiotoxicity of Residual Oil Fly Ash: Hazard Identification and Mechanisms of Injury

Citation:

Knuckles, T., R. Jaskot, J. Richards, Andy Miller, A. Ledbetter, J. Mcgee, Bill Linak, AND K. Dreher. Biokinetically-Based In Vitro Cardiotoxicity of Residual Oil Fly Ash: Hazard Identification and Mechanisms of Injury. Cardiovascular Toxicology. Humana Press Incorporated, Totowa, NJ, 13(4):426-37, (2013).

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 V levels that was 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 (3.13µg/mL) of ROFA-L 24h post-exposure. Dimethylthiourea (28mM) inhibited ROFA-L-induced cytotoxicity at high (25-12.5µg/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 phospho-tyrosine 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.

Purpose/Objective:

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 mechanisms of injury and cardiotoxicity of bioavailable constituents of residual oil fly ash (ROFA) employing in vivo, biokinetically-based, concentrations determined from their pulmonary deposition.

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Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 12/04/2013
Completion Date: 12/04/2013
Record Last Revised: 07/28/2014
Record Created: 12/04/2013
Record Released: 12/04/2013
OMB Category: Other
Record ID: 264111

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

ENVIRONMENTAL PUBLIC HEALTH DIVISION

CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH