Superfund Research Program
PCBs and Cytosolic Phenol and Steroid Sulfotransferases
Project Leader: Michael W. Duffel
Grant Number: P42ES013661
Funding Period: 2006-2020
Final Progress Reports
Project research during the past year has provided valuable new information that will enable assessment of the potential for sulfated metabolites to be significant contributors to the toxicities observed upon exposure to airborne polychlorinated biphenyls (PCBs). This has included the development of a rigorous method for analysis of PCB sulfates in human serum, wherein detection and quantitation of a total of 124 PCB sulfate congeners is now possible. The method involves tandem gas chromatographic/mass spectral analysis of hydroxylated PCBs in serum before and after hydrolysis of the PCB sulfates catalyzed by an affinity chromatography-purified sulfatase. While this enzyme is highly specific for sulfate esters, it utilizes a broad range of PCB sulfates. The procedure will now be applied to determine the concentrations of PCB sulfates in serum samples from mothers and their children. The researchers have also made progress in establishing parameters for LC/MS/MS analysis of four PCB sulfates in human urine samples (i.e., 4’-PCB 3 sulfate, 4-PCB 11 sulfate, 4’-PCB 25 sulfate, and 4-PCB 52 sulfate). These are metabolites that are derived from four major PCBs that are commonly detected in indoor air. The toxicological significance of these PCBs has been previously demonstrated. Additionally, during the past year, the researchers have completed collaborative studies on the interaction of key hydroxylated PCBs and PCB sulfates with thyroid hormone receptors and have investigated the specificity of human microsomal sulfatase for PCB sulfates. These studies significantly advance our understanding of the roles of metabolism in toxicities associated with airborne PCBs.