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

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.