Grouping of Petroleum Substances as Example UVCBs by Ion Mobility-Mass Spectrometry to Enable Chemical Composition-Based Read-Across

Abstract

Substances of Unknown or Variable composition, Complex reaction products, and Biological materials (UVCBs), including many refined petroleum products, present a major challenge in regulatory submissions under the EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and US High Production Volume regulatory regimes. The inherent complexity of these substances, as well as variability in composition obfuscates detailed chemical characterization of each individual substance and their grouping for human and environmental health evaluation through read-across. In this study, we applied ion mobility mass spectrometry in conjunction with cheminformatics-based data integration and visualization to derive substance-specific signatures based on the distribution and abundance of various heteroatom classes. We used petroleum substances from four petroleum substance manufacturing streams and evaluated their chemical composition similarity based on high-dimensional substance-specific quantitative parameters including m/z distribution, drift time, carbon number range, and associated double bond equivalents and hydrogen-to-carbon ratios. Data integration and visualization revealed group-specific similarities for petroleum substances. Observed differences within a product group were indicative of batch- or manufacturer-dependent variation. We demonstrate how high-resolution analytical chemistry approaches can be used effectively to support categorization of UVCBs based on their heteroatom composition and how such data can be used in regulatory decision-making.

Adding a new separation dimension to MS and LC–MS: What is the utility of ion mobility spectrometry?

“…Grimm et al. used TWIMS–MS for the study of unknown or variable composition biological materials, complex reaction products, and biological materials in petroleum samples . This workflow allowed mass‐to‐charge, drift time, and Hydrogen/Carbon ratio to be used to support compound classification and intersamples comparisons.…”

“…Further discussion of the potential of [148], with permission from the American Society for Biochemistry and Molecular Biology multidimensional chromatography in combination with IM-MS is presented in Section 8.3. Grimm et al used TWIMS-MS for the study of unknown or variable composition biological materials, complex reaction products, and biological materials in petroleum samples [153]. This workflow allowed mass-to-charge, drift time, and Hydrogen/Carbon ratio to be used to support compound classification and intersamples comparisons.…”

Optimal Chemical Grouping and Sorbent Material Design by Data Analysis, Modeling and Dimensionality Reduction Techniques

“…In addition, gaps in available toxicity data create challenges for regulatory decision-making on these substances. In this study, a measure of chemical composition of the reported UVCB substances was derived using Ion Mobility Mass Spectrometry (IM-MS) analysis (Grimm et al, 2017). IM-MS analysis provides chemical fingerprint of substance complexities by yielding the m/z (mass divided by charge number), drift time (time for each ion to traverse within a homogeneous electric field in the ion mobility spectrometer) and abundance.…”

Grouping of complex substances using analytical chemistry data: A framework for quantitative evaluation and visualization

“…Despite these advances, full chemical characterization of complex substances, such as petroleum UVCB substances, is still largely unattainable [6]. This presents a challenge for defining “sufficient similarity” for a substance of interest in comparison to those substances that may have already been tested for their potential human and ecological effects [9, 10].…”

“…Quantitative interpretation of high-dimensional data has been an active area of statistics and a number of algorithms have been applied to classify unknown samples, or to derive discriminating data features [8, 12]. For example, data integration, clustering and visualization techniques using ion mobility-mass spectrometry (IM-MS) data of a subset of UVCBs have been used to determine the group-specific similarities [13]. Comparative analyses have also been performed.…”