Polychlorinated biphenyls (PCBs) are a group of 209 individual congeners that differ widely in their toxic effects and mechanisms of toxicity. Most research has focused on the effects of higher chlorinated PCBs because they bioaccumulate. However, exposure to lower chlorinated, more volatile biphenyls through contaminated indoor and outdoor air can be very high for some populations. These airborne PCBs are readily bio-activated and exhibit their own, distinct spectra of toxic effects. We hypothesize that airborne PCBs can bring about inappropriate changes in the redox status and macromolecule function of cells and tissues through different, distinct mechanisms, leading to detrimental effects on health, and that through understanding these mechanisms, strategies to ameliorate these health effects can be designed. The discoveries we have made in the previous funding periods have fundamentally changed views on the toxicity of PCBs. Our data provided key information for the reclassification of PCBs to Group 1, human carcinogens, by the International Agency of Research on Cancer (IARC). Our new discoveries supply the foundation for the proposed research in this renewal application. To address the hypothesis of Project 1, we will study PCBs occurring most often in air, and their metabolites, to: 1) provide an in-depth analysis of the disruptions in the redox networks, redox environment, and basic energy metabolism-respiration of cells and tissues upon exposure; 2) identify the active congeners/metabolites to elucidate structure-activity relationships of (geno)toxicity, ranking them in importance and potential consequences to human health; 3) identify sensitive target tissues, analyze organ specificity, and determine threshold levels and toxicity; 4) examine the potential of dietary approaches to prevent or ameliorate toxicity; and 5) assess human mother-child samples with known PCB and metabolite body burdens to develop biomarkers of exposure and effects, and to identify potential susceptible subpopulations. Our principal goal is to gain new knowledge that will enable data-driven risk assessment, as well as chemo- protective and therapeutic methods to prevent or ameliorate the detrimental effects of PCBs and other toxicants. Our approach is integrative and diverse, ranging from fundamental physical chemistry, to detailed analysis of effects at the `molecule per cell' level, to dissection of the interactions between different congeners of PCBs, effects of micronutrients, and analysis of human samples to determine consequences of exposure. With a clear focus on our goals, this research program meets exceptionally well the mission of the Superfund Research Program, pushing the boundaries of science with a view to the future for effective hazard management and health protection.

Public Health Relevance

Project 1 of the Iowa Superfund Research Program will provide new knowledge on the toxic effects and mechanisms of toxicity of polychlorinated biphenyls (PCBs), a large family of environmental pollutants that cause many different types of adverse human health effects, including cancer. Data produced in this project will be essential for risk assessment, development of strategies to prevent or ameliorate toxicity, and for management of these toxicants in human environments. These data will provide federal, state, and local agencies, e.g. EPA and ATSDR, with needed information to determine courses of action to manage these environmental pollutants and protect human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES013661-10
Application #
8919611
Study Section
Special Emphasis Panel (ZES1-LWJ-J (SF))
Project Start
Project End
Budget Start
2015-09-30
Budget End
2016-03-31
Support Year
10
Fiscal Year
2015
Total Cost
$350,726
Indirect Cost
$114,116
Name
University of Iowa
Department
Type
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52246
Hou, Xingwang; Yu, Miao; Liu, Aifeng et al. (2018) Biotransformation of tetrabromobisphenol A dimethyl ether back to tetrabromobisphenol A in whole pumpkin plants. Environ Pollut 241:331-338
Xiao, Xin; Chen, Baoliang; Chen, Zaiming et al. (2018) Insight into Multiple and Multilevel Structures of Biochars and Their Potential Environmental Applications: A Critical Review. Environ Sci Technol 52:5027-5047
Herkert, Nicholas J; Jahnke, Jacob C; Hornbuckle, Keri C (2018) Emissions of Tetrachlorobiphenyls (PCBs 47, 51, and 68) from Polymer Resin on Kitchen Cabinets as a Non-Aroclor Source to Residential Air. Environ Sci Technol 52:5154-5160
P?n?íková, Kate?ina; Svržková, Lucie; Strapá?ová, Simona et al. (2018) In vitro profiling of toxic effects of prominent environmental lower-chlorinated PCB congeners linked with endocrine disruption and tumor promotion. Environ Pollut 237:473-486
P?n?íková, Kate?ina; Brenerová, Petra; Svržková, Lucie et al. (2018) Atropisomers of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) exhibit stereoselective effects on activation of nuclear receptors in vitro. Environ Sci Pollut Res Int 25:16411-16419
Robertson, Larry W; Weber, Roland; Nakano, Takeshi et al. (2018) PCBs risk evaluation, environmental protection, and management: 50-year research and counting for elimination by 2028. Environ Sci Pollut Res Int 25:16269-16276
Klaren, William D; Vine, David; Vogt, Stefan et al. (2018) Spatial distribution of metals within the liver acinus and their perturbation by PCB126. Environ Sci Pollut Res Int 25:16427-16433
Tomsho, Kathryn S; Basra, Komal; Rubin, Staci M et al. (2018) Correction to: Community reporting of ambient air polychlorinated biphenyl concentrations near a Superfund site. Environ Sci Pollut Res Int 25:16401
Uwimana, Eric; Li, Xueshu; Lehmler, Hans-Joachim (2018) Human Liver Microsomes Atropselectively Metabolize 2,2',3,4',6-Pentachlorobiphenyl (PCB 91) to a 1,2-Shift Product as the Major Metabolite. Environ Sci Technol 52:6000-6008
Herkert, Nicholas J; Hornbuckle, Keri C (2018) Effects of room airflow on accurate determination of PUF-PAS sampling rates in the indoor environment. Environ Sci Process Impacts 20:757-766

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