Portland Harbor Superfund Site
Our investigators work at the Portland Harbor Superfund site, located in a heavily industrialized stretch of the Willamette River.
PAHs and the Gulf of Mexico Oil Spill
We sampled the polycyclic aromatic hydrocarbons (PAHs) in air and water in the Gulf of Mexico before and after the Deepwater Horizon oil spill in 2010. The level of PAHs in crude oil varies between 0.2 and 7%, depending on location. Although this seems like a small percent, PAHs are a significant toxicological health concern.
Human PAH Micro-Dosing
Metabolism strongly influences the impact of exposures to pro-carcinogenic PAHs such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Little data has been available on the metabolism and pharmacokinetics in humans of high-molecular-weight PAHs such as DBC.
David Williams and former SRP investigator, Rick Corley, applied the exquisite sensitivity of accelerator mass spectrometry (AMS) and a novel "moving wire" interface between AMS and ultra-performance liquid chromatography to detect and quantify parent DBC and its major metabolites. This project created the first data set to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose. It provided the data necessary to translate high-dose experiments with animal models into actionable information of human risk assessment (16). This in vivo data set will prove to be a valuable addition to risk assessment paradigms. To extend this approach, Dr. Williams is now investigating interactions and dietary interventions in human subjects with funding from a new R01.
Establishing Representative Environmental Mixtures
The most comprehensive approach to understanding complex chemical mixture toxicity is to assess the toxicity of whole mixtures directly. The seemingly infinite number of potential mixtures in the environment limits the technical and economic feasibility of these approaches. It can be challenging to identify specific toxicants and to identify their mechanisms of action.
We applied the representative mixtures approach to create a well-defined mixture that allows us to compare directly the concentration-response curves of the mixture with those of the individual components. In 2010 and 2015, the Anderson Project deployed polyethylene passive sampling devices (PSDs) in surface water at 7 different sites in the Portland Harbor Superfund site (PHSS). The Chemistry Core prepared a surrogate mixture called Supermix 10 (SM10) that consisted of the 10 PAHs with the highest average concentrations in the environmental ratios. Tanguay evaluated the developmental toxicity of SM10 and the 10 individual constituents with the zebrafish model. We showed that SM10 and only 3 of the individual PAHs were developmentally toxic. Subsequently, we constructed and exposed developing zebrafish to two sub-mixtures: SM3 (comprised of 3 of the developmentally toxicity PAHs) and SM7 (composed of the 7 non-developmentally toxic PAHs). We found that the SM3 toxicity profile was nearly identical to the SM10 toxicity profile. The results demonstrated that the overall developmental toxicity in the mixtures was consistent with the general concentration addition model. We also confirmed that the AHR pathway activation correlated with the toxic mixtures and PAHs (17). Collectively, these results illustrate the utility of coupling the zebrafish capabilities with the representative mixtures approach. They create significant opportunities to support stakeholders’ challenges with mixtures.
Environmentally Transformed PAHs
Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are byproducts of combustion and photo-oxidation of parent PAHs. Anderson and Simonich demonstrated that OPAHs are stable and widely present in the environment (18). Before this Center-wide collaboration, it was unclear whether OPAHs pose a hazard to human health. The Tanguay group applied the developing zebrafish model to evaluate a structurally diverse set of 38 OPAHs. They conducted qRT-PCR -for a number of oxidative stress genes, including the glutathione transferase, glutathione peroxidase, and superoxide dismutase (sod) families. Hierarchical clustering of the structure-activity outcomes indicated that the most toxic of the OPAHs contained either adjacent diones on 6-carbon moieties or terminal para-diones on multi-ring structures. Five-carbon moieties with adjacent diones were among the least toxic OPAHs. The toxicity of multi-ring structures with more centralized para-diones varied considerably. 1,9-benz-10-anthrone (BEZO), xanthone (XAN), and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) exposures increased expression of several genes related to oxidative stress and also decreased oxygen consumption rate, a measurement of mitochondrial respiration (19).
This comprehensive in vivo characterization of 38 structurally diverse OPAHs revealed differential AHR dependency and a prominent role for oxidative stress in the toxicity mechanisms. Further mechanistic evaluations into the toxicity of 7,12-B[a]AQ and BEZO confirmed that the toxicity of both OPAHS are AHR2 dependent, but the transcriptional responses downstream of AHR for these two environmentally relevant OPAHS are distinct (20). We also identified and characterized a novel noncoding RNA (SlincR) induced by 7,12-B[a]AQ (21). SlincR, an evolutionary conserved bonafide AHR target gene, regulates important genes during development and in response to AHR activation (22).
Tribal Environmental Health Summit 2018
On June 25-26, 2018 the OSU/PNNL Community Engagement Core hosted the 3rd Tribal Environmental Health Summit. This bi-annual two-day brings together Native American and Alaskan Native researchers and non-Indigenous researchers to discuss issues of environmental health among Native Americans. This event brought together more than 130 individuals from different tribes, universities, and government agencies. The event allowed scientists to network and explore career paths, while stakeholders learned about issues that affect tribal communities. All presentations were recorded and available for viewing below. For a list of presentation videos go to: https://superfund.oregonstate.edu/conducting-research-tribal-communities
The program (http://blogs.oregonstate.edu/tehs2018/summit-program/) shows the diverse speakers.