The Next Frontier of Environmental Unknowns: Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological Materials (UVCBs)

Abstract

Substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) are over 70 000 "complex" chemical mixtures produced and used at significant levels worldwide. Due to their unknown or variable composition, applying chemical assessments originally developed for individual compounds to UVCBs is challenging, which impedes sound management of these substances. Across the analytical sciences, toxicology, cheminformatics, and regulatory practice, new approaches addressing specific aspects of UVCB assessment are being developed, albeit in a fragmented manner. This review attempts to convey the "big picture" of the state of the art in dealing with UVCBs by holistically examining UVCB characterization and chemical identity representation, as well as hazard, exposure, and risk assessment. Overall, information gaps on chemical identities underpin the fundamental challenges concerning UVCBs, and better reporting and substance characterization efforts are needed to support subsequent chemical assessments. To this end, an information level scheme for improved UVCB data collection and management within databases is proposed. The development of UVCB testing shows early progress, in line with three main methods: whole substance, known constituents, and fraction profiling. For toxicity assessment, one option is a whole-mixture testing approach. If the identities of (many) constituents are known, grouping, read across, and mixture toxicity modeling represent complementary approaches to overcome data gaps in toxicity assessment. This review highlights continued needs for concerted efforts from all stakeholders to ensure proper assessment and sound management of UVCBs.

The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

“…While initial efforts such as the mixture InChI (MInChI) show promise (see e.g ., Fig. 3 in [ 51 ]), there is room for further developments. Organometallic compounds (e.g., methylmercury compounds, organolead/organotin compounds, cyclic volatile methylsiloxanes, gadolinium compounds used as contrast agents) are cases that can be handled to an extent with the current approaches (although not in an “MS-ready” form).…”

“…Associated InChIKey lists were only generated for known structures. Dealing with partially characterized molecular features or chemical substances of Unknown or Variable Composition, Complex Reaction Products or Biological Materials (UVCB substances, UVCBs) is a subject of future collaborations beyond the scope of the current article (see e.g., [ 50 , 51 ]), as discussed further below.…”

Paths to Cheminformatics: Q&A with Norberto Sánchez-Cruz and Emma Schymanski

“…findable, accessible, interoperable and reusable [8,9]) in these fields, to alleviate several bottlenecks [10][11][12]. We also invest efforts into tackling some really tough cheminformatics challenges that are holding back environmental science and exposomics from making progress, such as UVCBs (materials of unknown or variable composition, complex reaction products or biological materials) [13]. In the future, I hope that our current efforts will soon solve current problems so we can move onto the next set of interesting challenges!…”

From descriptors to intrinsic fish toxicity of chemicals: an alternative approach to chemical prioritization

“…2,10 Most of these chemicals are structurally unknown with little to no knowledge about their fate nor toxicity. [1][2][3][4][5]10,11 Moreover, experimental assessment of the fate and toxicity of such a large number of chemicals in not feasible, resulting in wider application of modeling approaches. [12][13][14][15] Prediction of the physiochemical properties and the biological activity (e.g.…”