Integrative Chemical–Biological Grouping of Complex High Production Volume Substances from Lower Olefin Manufacturing Streams

Abstract

Human cell-based test methods can be used to evaluate potential hazards of mixtures and products of petroleum refining (“unknown or variable composition, complex reaction products, or biological materials” substances, UVCBs). Analyses of bioactivity and detailed chemical characterization of petroleum UVCBs were used separately for grouping these substances; a combination of the approaches has not been undertaken. Therefore, we used a case example of representative high production volume categories of petroleum UVCBs, 25 lower olefin substances from low benzene naphtha and resin oils categories, to determine whether existing manufacturing-based category grouping can be supported. We collected two types of data: nontarget ion mobility spectrometry-mass spectrometry of both neat substances and their organic extracts and in vitro bioactivity of the organic extracts in five human cell types: umbilical vein endothelial cells and induced pluripotent stem cell-derived hepatocytes, endothelial cells, neurons, and cardiomyocytes. We found that while similarity in composition and bioactivity can be observed for some substances, existing categories are largely heterogeneous. Strong relationships between composition and bioactivity were observed, and individual constituents that determine these associations were identified. Overall, this study showed a promising approach that combines chemical composition and bioactivity data to better characterize the variability within manufacturing categories of petroleum UVCBs.

Informing Hazard Identification and Risk Characterization of Environmental Chemicals by Combining Transcriptomic and Functional Data from Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes

“…We provide transcriptomic and phenotypic POD information on a large number of environmental chemicals in iPSC-derived cardiomyocytes-a cell type that is often most sensitive (i.e., has the lowest PODs) when compared to other human cell types. The latter has been reported for a wide range of compounds and chemical classes, − complex substances, ,, and environmental mixtures. , Thus, we reason that quantitative estimates of chemical effects from this study, both functional and transcriptomic, may be used as conservative in vitro PODs. When PODs were used for risk characterization using BER, we found relatively few chemicals would be flagged with BER < 1 (for drugs) or <100 (for environmental chemicals).…”