Project Summary (2025-2030)

The Iowa Superfund Research Program (ISRP) at the University of Iowa investigates the sources and exposure consequences of airborne polychlorinated biphenyls (PCBs), a 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. One significant challenge of studying PCBs is the sheer number of PCB congeners, which totals 209. Additionally, there exist 837 different congeners for each class of PCB metabolite, including mono-hydroxylated (OH-PCBs), sulfated (OH-PCB sulfates), and others. Most of these PCB derivatives are either not available from commercial sources or have never been synthesized. Moreover, obtaining PCB mixtures or individual PCB congeners from commercial sources can be expensive, especially in large quantities, and their independent authentication and confirmation of purity are still necessary before use.

To facilitate the innovative studies proposed by the ISRP research projects, there is a critical need for a Synthesis Core (SC) that makes PCB mixtures, individual PCB congeners, and their metabolites available for a broad range of studies on the volatilization, transport, exposure, toxicity, and remediation of PCBs. The main objective of the SC, a small but critical and well- integrated Research Support Core of the ISRP, is to address this need by providing a large variety of well- authenticated and highly pure PCB mixtures and PCB derivatives in a timely and cost-efficient manner to all research projects and research support cores within the ISRP. To attain this objective, the SC will: synthesize and maintain a broad range of PCB derivatives, mostly using synthetic approaches developed in previous funding cycles by SC researchers; employ rigorous guidelines established by ISRP researchers for the authentication of these key chemicals; in collaboration with the DMAC, document the authentication of PCB mixtures and PCB derivatives following the FAIR principles in appropriate repositories, and consult on the safe handling PCBs and other hazardous chemicals.

The Specific Aims of the ISRP Synthesis Core are to:

1) Maintain and prepare PCB mixtures and pure PCB congeners;

2) Prepare methoxylated and hydroxylated PCB derivatives;

3) Synthesize OH-PCB sulfate metabolites; and

4) Prepare miscellaneous compounds, including diazomethane.

The timely and cost-efficient availability of PCB mixtures, individual PCBs, OH-PCBs, OH-PCB sulfates, and other PCB metabolites will enhance and, in some cases, enable the innovative studies proposed by ISRP research projects. Moreover, the use of test compounds with well-documented authentication across several research projects will improve the rigor and reproducibility of ISRP research.