Polychlorinated Biphenyls as a Cardiovascular Health Risk: A New Threat from an Old Enemy?

Polychlorinated biphenyls (PCBs) were produced in the United States beginning in 1929.1 Evidence of their negative impact on human health emerged very early in their industrial-scale production,2 and studies published in the 1960s confirmed that PCB contamination was widespread and persistent in both the environment and people’s bodies.1 Despite their eventual discontinuation,3 PCB legacy materials and persistent environmental contamination continue to be sources of environmental release and exposure even now.4 In a recent report in Environmental Health Perspectives, investigators proposed an integrated new approach for evaluating the cumulative effects of PCBs on heart health using in vitro bioactivity in human endothelial cells and cardiomyocytes.5

PCB exposure has been associated with skin conditions, diabetes, liver toxicity, cancer, and deficits in immune and neurological function in a number of human health studies.6 How PCBs affect cardiovascular health, however, has been relatively understudied despite reports linking dietary exposure to hypertension and increased risk of heart disease.7,8 Recent breakthroughs in stem cell technology have had a substantial impact on our ability to better understand the potentially harmful effects of PCBs, says study leader Ivan Rusyn, a professor in the Texas A&M University Department of Veterinary Integrative Biosciences and director of the university’s Superfund Research Center.

Environmental PCB pollution comes from both legacy sources (such as electrical transformers) and novel sources (such as pigments and paints). Contaminated shellfish and fish are a common source of human exposure. Images, left to right: Sturmovik/CC 3.0; © iStockphoto/MPKphoto; © iStockphoto/tacojim.

The number and position of chlorine atoms in the PCB molecule can vary widely, giving rise to a complex array of chemical structures and metabolites. Thus, only a small number of PCBs have been evaluated for human health effects.9 For the new study, researchers selected and synthesized 25 parent compounds and metabolites representing PCB congeners of public health interest. The test library included compounds that continue to be detected in air samples in schools due to emission from building materials, as well as legacy PCBs associated with paint and pigment manufacturing.4

The inclusion of PCB metabolites makes this study unique, notes Brian Berridge, scientific director of the Division of the National Toxicology Program at the National Institute of Environmental Health Sciences, who was not involved in the study. This approach is particularly important because metabolism of a parent compound can have dramatic effects on its toxicity: Higher-chlorinated PCBs are more resistant to metabolism and are therefore retained in the body, whereas lower-chlorinated compounds are rapidly metabolized and excreted.10

The researchers used in vitro assays to assess how individual compounds may affect cardiomyocytes and endothelial cells, using measures of cardiomyocyte function such as beat frequency and endothelial blood vessel formation as end points. These tests revealed that the PCBs and metabolites tested were bioactive in both cell types.

Next, they used two approaches to estimate the cardiovascular health risk posed by these compounds. First, they used a “read-across” approach to estimate hazard by comparing the chemistry of the compounds to biological effects of previously characterized compounds of similar structure. Second, they incorporated available exposure data to translate the in vitro results into estimated population risk.

The use of these methods in combination allowed the researchers to fill in data gaps and infer effects of compounds that have not been previously tested based on data available for compounds of similar structure. “Both of these methods demonstrate how new approach methodologies can and should be used by the regulators, and we hope that this case study is informative to decision makers,” says Rusyn.

Given the sheer number of compounds that remain to be tested for their impacts on human health, assessing their in vivo effects individually would entail exponential increases in study complexity that would be time- and cost-prohibitive.11,12 The predictive approaches used in this study exemplify current trends in toxicology research that aim to increase the efficiency of risk assessment. Scott Masten, director of the Office of Nomination and Selection at the National Toxicology Program, who also was not involved in the study, notes that despite the usefulness of read-across approaches in research, they are most often used to prioritize decisions rather than make a final determination in regulatory matters.

“Studies like ours [taken in isolation], quantitatively characterizing the hazards and population variability, cannot fully address the risk as we don’t have a good handle on exposure characterization for most chemicals in the environment,” concludes Rusyn. He adds that future endeavors should also focus on advances in exposure assessment. He points to work such as that undertaken by research centers, including the University of Iowa Superfund Research Program, where multidisciplinary collaborations13 span the breadth of addressing environmental pollution from exposure to continued release and, finally, to remediation.