Synthesis Core The Superfund Research Program at The University of Iowa (ISRP) supports investigations of the consequences of sources and exposures to all airborne polychlorinated biphenyls (PCBs), an important class of Superfund chemicals. ISRP biomedical and environmental research projects require a variety of study compounds ranging from technical and synthetic PCB mixtures to pure PCB congeners and their metabolites for studies of the volatilization, transport, exposure, toxicity, and remediation of these PCB congeners. A major obstacle for these studies is the large number of 209 PCB congeners plus the large number of 837 possible mono-hydroxylated (OH-PCBs), sulfated (PCB sulfates), glucuronidated (PCB glucuronides) and other PCB metabolites. Many of these PCB derivatives are not available from commercial sources or have never been synthesized before. Obtaining PCB mixtures or individual PCB congeners from commercial sources can also be expensive, especially if large quantities are needed for animal studies. Moreover, information about their synthesis is typically not available from commercial sources. To facilitate the innovative studies proposed by individual ISRP research projects, there is a critical need to make sufficient quantities of PCBs and their metabolites available for studies investigating the volatilization, transport, exposure, toxicity, and remediation of PCBs. To address this critical need, the major objective of the Synthesis Core is to provide a large variety of well-authenticated and highly-pure PCB derivatives in a timely and cost-efficient manner to ISRP and, as time and resources allow, other researchers. To attain this objective, the Synthesis Core will synthesize and maintain a broad range of PCB derivatives and employ rigorous guidelines for the authentication of these key chemicals. At the same time, the Synthesis Core will continue to develop novel synthetic strategies for the synthesis of PCB congeners and PCB metabolites as needed by ISRP researchers.
The Specific Aims of the ISRP Synthesis Core are to: 1) maintain and prepare PCB mixtures and pure PCB congeners; 2) prepare hydroxylated PCB derivatives; 3) synthesize PCB sulfate metabolites; and 4) prepare miscellaneous compounds, such as: PCB hydroquinones, PCB catechols, PCB quinones, and PCB glutathione and N- acetylcysteine conjugates. The timely availability of PCB mixtures, individual OH-PCBs, PCB sulfates and other PCB metabolites will greatly enhance and, if the respective PCB metabolites are unavailable from commercial sources, enable the innovative studies proposed by ISRP Research Projects. Moreover, the use of well-authenticated test compounds across several ISRP research projects will greatly enhance the rigor and reproducibility of ISRP research.

Public Health Relevance

Synthesis Core The Synthesis Core of the Superfund Research Program at The University of Iowa (ISRP) supports investigations of the consequences of sources and exposures to all airborne polychlorinated biphenyls (PCBs), an important class of Superfund chemicals, by providing PCB mixture, individual PCB congeners and PCB metabolites to ISRP researchers for laboratory studies and as analytical standards. The availability of authenticated test compounds in a timely and cost-efficient manner is relevant to the mandate of the Superfund Research Program because it will enable the innovative studies proposed by ISRP research projects and enhance the rigor and reproducibility of ISRP research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES013661-16
Application #
10135993
Study Section
Special Emphasis Panel (ZES1)
Project Start
2006-05-12
Project End
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
16
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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
Herkert, Nicholas J; Spak, Scott N; Smith, Austen et al. (2018) Calibration and evaluation of PUF-PAS sampling rates across the Global Atmospheric Passive Sampling (GAPS) network. Environ Sci Process Impacts 20:210-219
Dhakal, Kiran; Gadupudi, Gopi S; Lehmler, Hans-Joachim et al. (2018) Sources and toxicities of phenolic polychlorinated biphenyls (OH-PCBs). Environ Sci Pollut Res Int 25:16277-16290
Enayah, Sabah H; Vanle, Brigitte C; Fuortes, Laurence J et al. (2018) PCB95 and PCB153 change dopamine levels and turn-over in PC12 cells. Toxicology 394:93-101
Klinefelter, Kelsey; Hooven, Molly Kromme; Bates, Chloe et al. (2018) Genetic differences in the aryl hydrocarbon receptor and CYP1A2 affect sensitivity to developmental polychlorinated biphenyl exposure in mice: relevance to studies of human neurological disorders. Mamm Genome 29:112-127
Gourronc, Francoise A; Robertson, Larry W; Klingelhutz, Aloysius J (2018) A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor. Environ Sci Pollut Res Int 25:16481-16492
Alam, Sinthia; Carter, Gwendolyn S; Krager, Kimberly J et al. (2018) PCB11 Metabolite, 3,3'-Dichlorobiphenyl-4-ol, Exposure Alters the Expression of Genes Governing Fatty Acid Metabolism in the Absence of Functional Sirtuin 3: Examining the Contribution of MnSOD. Antioxidants (Basel) 7:
Li, Xueshu; Holland, Erika B; Feng, Wei et al. (2018) Authentication of synthetic environmental contaminants and their (bio)transformation products in toxicology: polychlorinated biphenyls as an example. Environ Sci Pollut Res Int 25:16508-16521
Sethi, Sunjay; Keil, Kimberly P; Lein, Pamela J (2018) 3,3'-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism. Arch Toxicol 92:3337-3345

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