Risk Characterization of Environmental Samples UsingIn VitroBioactivity and Polycyclic Aromatic Hydrocarbon Concentrations Data

Abstract

Methods to assess environmental exposure to hazardous chemicals have primarily focused on quantification of individual chemicals, although chemicals often occur in mixtures, presenting challenges to the traditional risk characterization framework. Sampling sites in a defined geographic region provide an opportunity to characterize chemical contaminants, with spatial interpolation as a tool to provide estimates for non-sampled sites. At the same time, the use of in vitro bioactivity measurements has been shown to be informative for rapid risk-based decisions. In this study we measured in vitro bioactivity in 39 surface soil samples collected immediately after flooding associated with Hurricane Harvey in Texas in a residential area known to be inundated with polycyclic aromatic hydrocarbon (PAH) contaminants. Bioactivity data were from a number of functional and toxicity assays in five human cell types (induced pluripotent stem cell (iPSC)-derived hepatocytes, cardiomyocytes, neurons and endothelial cells, as well as human umbilical vein endothelial cells (HUVEC). Data on concentrations of PAH in these samples was also available and the combination of data sources offered a unique opportunity to assess the joint spatial variation of PAH components and bioactivity. We found significant evidence of spatial correlation of a subset of PAH contaminants and of cell-based phenotypes. In addition, we show that the cell-based bioactivity data can be used to predict environmental concentrations for several PAH contaminants, as well as overall PAH summaries and cancer risk. This study’s impact lies in its demonstration that cell-based profiling can be used for rapid hazard screening of environmental samples by anchoring the bioassays to concentrations of PAH. This work sets the stage for identification of the areas of concern and direct quantitative risk characterization based on bioactivity data, thereby providing an important supplement to traditional individual chemical analyses by shedding light on constituents that may be missed from targeted chemical monitoring.

Potential Human Health Hazard of Post-Hurricane Harvey Sediments in Galveston Bay and Houston Ship Channel: A Case Study of Using In Vitro Bioactivity Data to Inform Risk Management Decisions

“…Samples were freeze-dried before extraction for in vitro bioactivity screening. Biologically available fraction of each sediment sample was extracted using DMSO and cyclohexane as detailed elsewhere [ 11 ] using the standard method [ 19 ]. Briefly, 2 mL of cyclohexane and 2 mL of DMSO pre-equilibrated with cyclohexane at 10:1 ratio was added to 1 g of freeze-dried sediment sample and the suspension was thoroughly mixed by vortexing for at least 1 min.…”

“…We selected these cell types because many of the environmental chemicals expected to be present in tested sediments are known to be associated with hepatotoxicity, neurotoxicity, cardiotoxicity, and vascular toxicity (see literature review of the effects of Superfund priority list chemicals on different organs in [ 20 ]). We have published methods for using iPSC-derived cells [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ] to assess the toxicity of the individual chemicals [ 20 , 28 , 29 , 30 , 31 , 32 ], whole mixtures [ 11 , 16 ], and complex substances [ 33 , 34 ]. The reasons we chose iPSC-derived cells are because: (i) these cells are more physiological than immortalized cell lines and can be derived for different tissues/organs [ 35 ]; (ii) they can be obtained from the same individual(s) to enable highly reproducible experiments [ 36 ]; (iii) despite some limitations with the degree of maturation, these cells compare well to primary cells in terms of their function and expected organ-specific toxicity [ 35 , 37 , 38 ]; and (iv) a small number of iPSC-derived cell types can be as informative about hazard and safety margins as the larger set of in vitro models [ 33 ], or many ToxCast bioassays [ 20 ].…”

“…The U.S. EPA priority 16 PAHs as well the total PAH concentrations in sediment samples were analyzed by Geochemical and Environmental Research Group at Texas A&M University as previously reported [ 4 ]. Bioactivity data (POD values for each cell type) and PAH concentrations were used for the analysis of potential correlation with spatial locations as detailed elsewhere [ 11 ]. Tests of spatial association for bioactivity or PAH data were performed using the standard Mantel approach [ 41 ], where the time dimension in the original method can be substituted with any type of multivariate outcome.…”

“…Final predictions were returned to the original scale by multiplying each column by the original standard deviation and adding the original mean. The details of the prediction approach and parameter tuning are detailed elsewhere [ 11 ].…”

“…Indeed, the successful application of untargeted analytical methods to disaster research response has been demonstrated recently for events that occurred in the Houston/Galveston Bay area [ 9 , 10 ]. Similarly, biological assays show the potential to facilitate identification of mixtures that may pose human and/or environmental health risks [ 11 , 12 , 13 ]. Finally, computational approaches have also been developed, many of them based on utilizing the information from both exposure characterization and bioactivity measurements, to identify the chemicals of concern in mixtures that may be the drivers to the overall bioactivity [ 14 , 15 , 16 ].…”