Advances in chemistry, physics, cell biology, and computational modeling provide unique opportunities to improve human health risk assessments, according to Richard Corley, Ph.D. In an April 6 talk for the NIEHS Keystone Science Lecture series, he discussed cutting-edge technologies that make scientific predictions more relevant to humans and real-world conditions. For example, a new model of how air pollutants move through the atmosphere indicates that they stay in the air longer and travel farther than previous models have predicted.
“Dr. Corley’s work is particularly relevant to the institute’s Strategic Plan goal 4, which includes addressing combined exposures and chemical mixtures,” said Danielle Carlin, Ph.D., who hosted Corley’s talk. “Today’s lecture is a great opportunity to highlight work related to that goal and important research efforts through the Superfund Research Program.”
Corley recently retired as a lead researcher at the Oregon State University (OSU) Superfund Research Program (SRP) Center and laboratory fellow at Pacific Northwest National Laboratory (PNNL). He has been involved with cutting-edge research to improve how scientists relate data from cell systems to whole organisms, from animal studies to humans, and from generic models to realistic scenarios.
PAH effects differ between species and life stages
Corley highlighted OSU SRP Center studies on a complex group of chemicals called polycyclic aromatic hydrocarbons (PAHs). Little is understood about their movement and interactions in the body.
Using a novel modeling approach called integrated multiscale modeling, Corley and his colleagues study PAH compounds and their metabolites to predict how PAHs are distributed in the body.
Another new approach helps scientists to understand how different life stages affect the body’s metabolism and excretion of PAHs. This technique, called activity-based protein profiling, showed that a protein responsible for removing PAHs from the body changed activity levels during different life phases.
“Clearly understanding how PAHs interact with each other and with their metabolites in a real organism, as well as how protein activity influences the absorption, distribution, metabolism, and excretion of these chemicals across the life course, is crucial,” said Corley. “We’re incorporating this information into computational models ... so that we can better predict exposure and risk.”
Global transport of air pollutants
Corley also highlighted research to better predict the fate and movement of PAHs in the atmosphere. The effort is a collaboration between the OSU SRP Center, the NIEHS-supported Environmental Health Sciences Center at OSU, and several research teams at PNNL.
PAHs, which are present at many Superfund sites, are produced during combustion processes, such as the burning of wood and other fuels. Traditional models assume that contaminants like PAHs are broken down over time by oxidation which means that the concentration in the air and the distance those chemicals travel should decrease. However, researchers have found that part of the structure of aerosol particles shields them from being broken down.
“The shielding effect means PAHs are going to remain at higher levels in the air and travel farther than we thought before,” Corley noted. “The computational predictions are a much better match for real-world measurements of PAHs in air.”
“This improved model has important implications for human exposure and risk assessment not only for PAHs, but for other chemicals that were previously thought to be degraded during aerosol transport,” he added.
Crowell SR, Sharma AK, Amin S, Soelberg JJ, Sadler NC, Wright AT, Baird WM, Williams DE, Corley RA. 2013. Impact of pregnancy on the pharmacokinetics of dibenzo[def,p]chrysene in mice. Toxicol Sci 135(1):48–62.
Shrivastava M, Lou S, Zelenyuk A, Easter RC, Corley RA, Thrall BD, Rasch PJ, Fast JD, Massey Simonich SL, Shen HHuizhon S, Tao S. 2017. Global long-range transport and lung cancer risk from polycyclic aromatic hydrocarbons shielded by coatings of organic aerosol. Proc Natl Acad Sci U S A. 114(6):1246–1251.
(Adeline Lopez is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)