Environmental Health Sciences doctoral student Monika Roy recently received a three-year, $114,072 F31 Predoctoral Fellowship Award from the National Institutes of Health (NIH) to investigate the liver toxicity potential of the environmental chemical 3,3’-dichlorobiphenyl, or PCB-11. PCB-11 is primarily a byproduct of yellow pigment manufacturing, but is also found in sealants, resins, and other consumer products where it can eventually evaporate and be inhaled by humans.
The fellowship, funded through the Ruth L. Kirschstein Predoctoral Individual National Research Service Award (NRSA) program, enables promising predoctoral students with potential to develop into productive, independent research scientists, to receive financial support to conduct their own dissertation research.
“I’m honored to have been selected for this fellowship,” says Roy, who works under the supervision of Associate Professor of Environmental Health Sciences Alicia Timme-Laragy. “This study originated from a pilot grant awarded to Alicia that revealed interesting results and promising future directions, but I wouldn’t be able to continue it without this award, as our lab currently doesn’t have any funding for it.”
In 2015, Timme-Laragy was awarded a UMass Amherst Public Service Endowment grant examining whether Pioneer Valley paper mills and paper recycling facilities were unintentionally releasing the chemical PCB-11 into the environment. Roy participated in the laboratory portion of the pilot project to assess whether PCB-11 affects liver enzyme function using the zebrafish (Danio rerio) embryo model.
Roy’s F31 project will build on that initial line of investigation by examining how PCB-11 and PCB-11 metabolites, alone and in combination with other environmental chemicals, induce toxicity through the liver’s metabolism system in the zebrafish model. Roy’s work will also examine whether chronic exposures to PCB-11 or its metabolites leads to excessive fat buildup in the liver, also known as hepatic lipid accumulation.
In 1979, the U.S. Environmental Protection Agency banned the use of “higher-chlorinated” PCBs, such as those found in electrical equipment and hydraulic fluids after they were proven hazardous. Known associated health risks include their contributions to non-alcoholic fatty liver disease (NAFLD). With an estimated 30-40% of the U.S. population affected by it, NAFLD contributes an estimated U.S. economic burden of $103 billion per year. NAFLD is also prevalent in children and adolescents, affecting 34.2% of obese individuals and 7.6% of this population overall.
However, much less is known about how “lower-chlorinated” PCBs, like PCB-11, the most common chemical in this class, interact with the liver.
“While these chemicals are thought to be less hazardous because of their chemical structure, there’s been little toxicology research to demonstrate that,” notes Roy.
PCB-11 has been widely detected in air samples in both urban and rural areas, and in environmental and human samples, including in pregnant women. Roy says that understanding how PCB-11 affects liver enzyme function, especially in the context of increasingly urbanized areas where exposures to both PCB-11 and other environmental contaminants occur will be useful for public health researchers and regulators to know. Roy indicates that PCB-11 can potentially affect drug-drug interactions in the liver, and spoke about this in UMass Amherst’s Three Minute Thesis competition, where she placed 1st out of 50 competitors.
Roy has found thus far that acute developmental exposures to PCB-11 alone do not result in overt toxicological outcomes in zebrafish, but that it can misregulate liver-associated genes, stunt liver development, and seems to increase lipid droplet formation in liver tissue. Further, in combination with other environmental chemicals, PCB-11 may inhibit, or shut down, healthy liver enzyme activity needed for the body to metabolize certain chemical exposures in the environment.
Roy will set out to determine the toxicity contribution of phenolic and sulfate PCB-11 metabolites in 4-day old fish, and again assess toxicity in 30-day juvenile stage fish after low-dose chronic single and mixture exposures. Additionally, she will conduct a number of proposed training techniques and assays to gain practical experience in regulatory toxicity approaches and to increase preparation for her career goal of working as a scientist to assess the public health impacts of contaminant exposures.
“I hope this particular line of research will be of great use to public health regulatory agencies,” says Roy. “There isn’t a whole lot of research out there that examines this class of compounds. My hope is that this research characterizes how this chemical affects the liver, and provides some insight into whether this environmental contaminant is a public health risk.”