Environmental risk assessment and testing of UVCBs through balanced consideration of whole substances and representative constituent data: a tripartite perspective

Complex substances such as multiconstituent substances and substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) usually result from industrial processing, extraction of natural substances, or chemical reactions. Because of the variable and complex nature of source materials and the potential variability inherent to production processes, these substances can contain many, sometimes uncharacterized, constituents whose concentrations may vary between production batches. These UVCBs make up similar to 20%-25% of substances registered under regulatory frameworks globally. To identify and advance the various challenges associated with UVCB testing and assessment, the Health and Environmental Sciences Institute (HESI) organized the international workshop "Exploring the Complexities of UVCB Testing and Risk Assessment." The HESI UVCB workshop was aimed at initiating multisectoral tripartite discussions on the advantages and disadvantages of whole substance versus representative constituent testing and assessment approaches, identifying further research needs, and establishing potential consensus for solutions for UVCB environmental risk assessment. Ultimately, the insight from the workshop contributed to the further refinement and strengthening of the exposure-centric tiered approach developed previously for consideration in the environmental risk assessment of UVCBs and multiconstituent substances. More specifically, it contributed to developing a systematic process to efficiently balance the characterization and testing of the whole substance and representative constituents to ensure the assessment of UVCBs is fit for purpose.Key Points The testing and assessment of substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) cannot be systematized, but it requires a case-by-case evaluation that depends on the question to be answered, and includes some expert judgement. The assessment of UVCBs is best addressed using a weight-of-evidence approach. The testing and assessment of UVCBs involves the strategic collection and use of whole substance and representative constituent information, which we assist by providing a list of guiding questions.