The Synthesis Core directly supports the research function of the University of Iowa SBRP research program by providing a PCB exposure mixture as well as individual PCB congeners and PCB metabolites. In support of the Analytical Core, this core will also provide analytical standards.
Specific Aim 1 is the preparation of analytical and quality control/assurance standards for the Analytical Core. In close collaboration with the Analytical Core, which is responsible for purity control of PCB congeners and testing of prepared standards against certified Standard Reference Materials, the Synthesis Core will acquire or synthesize individual PCB congeners and prepare stock solutions for use as PCB calibration mixtures.
Specific Aim 2 is the preparation of an airborne PCB exposure mixture for in vitro and in vivo studies for Research Projects #1, #2, #3, and # 5. This exposure mixture will approximate the PCB congener profile of the mean Chicago PCB signal. The mixture will be prepared in close cooperation with the Analytical and Inhalation Toxicology Cores by mixing of Aroclor 1242, Aroclor 1254 and individual PCB congeners.
Specific Aim 3 is the synthesis of PCB congeners to supplement the PCB exposure mixture in Aim 2 and for use with the in vitro and in vivo studies of Research Projects #1, #2, #3, and # 5. These PCB congeners will also be available to the Analytical Core for the preparation of analytical and quality control/assurance standards.
Specific Aim 4 is the synthesis of methoxylated and hydroxylated PCB metabolites. Hydroxylated PCB metabolites will be used by Projects #1, #2, #3, and #5 for in vitro and in vivo studies. Both the hydroxylated and methoxylated PCB derivatives will be provided to the Analytical Core and individual research projects as analytical standards for the identification and quantification of (unknown) metabolites.
Specific Aim 5 is the synthesis of quinoid metabolites of PCBs and their glutathione conjugates for Research Projects #1 and #2.
Specific Aim 6 will provide PCB sulfates needed by Project #3. All compounds will be synthesized, if necessary in large (gram) quantities, with straightforward synthetic approaches that are well established at the University of Iowa. Drawing on their extensive experience with the synthesis of organohalogen compounds, Synthesis Core staff will be able to synthesize every compound of interest to the individual research projects.
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