Advancing Regulatory Decision Making of UVCB Substances Through Novel Analytical Techniques

Abstract

Substances of unknown and variable composition, complex reaction product and biological material (UVCB) are one of the most challenging areas in regulatory science and risk assessment. The obscured compositional characterization and understanding of these substances, such as petroleum products, have relied in broad physical-chemical properties to deduce their toxicological fate and behavior. This study aims to advance the risk assessment of UVCB substances through high-resolution mass spectrometry to comprehensively deconvolute their inherently complex and variable chemical composition at a molecular level. Ion mobility coupled with quadruple-time of flight- mass spectrometer (IMS-MS) was employed to rapidly screen petroleum UVBC substances to define the value of petroleomic characterization in regulatory decision making. First, we employed comprehensive IMS-MS acquired compositional profiles of crude oil for categorization based on their geographical source. We compared high-resolution information with that from conventional methods, establishing IMS-MS as a high-throughput and highly informative tool for the evaluation of UVCB substances. Then, we demonstrated the value of isobaric and isomeric characterization afforded by IMS-MS to comprehensively define molecular compositional profiles of petroleum refined products. High-resolution qualitative and semi-quantitative compositional information served to measure the degree of commonality across production cycles and between categories of UVCB substances to assist read-across and forensic fingerprinting assessments. Lastly, we assessed the environmental fate and behavior of weathered and photooxidized oil slick with high-resolution characterization of the dissolved organic matter from a mesocosm experiment. Through evaluation of molecular compositional trends, we determined that the physicochemical transformations of the composition of UVCBs correlated with sunlight irradiation achieving a better understanding of the environmental fate of an oil slick due to weathering to define the potential exposures and hazards. Together, this work demonstrated the utility of IMS-MS for rapid and comprehensive structural and molecular characterization of petroleum UVCB substances at a qualitative and semi-quantitative level. Through this dissertation we contribute a novel approach for the characterization of UVCB substances ensuring no underestimation of related human health and environmental hazards to support regulatory science and safeguard the risk assessments.