Critical Review of in Vitro Dosing Methods for Difficult-to-Test Substances and Hydrocarbon UVCBs

HESI Global’s UVCB Committee is pleased to share a new critical review in Environmental Toxicology and Chemistry: “Critical review of in vitro dosing methods for difficult-to-test substances and hydrocarbon UVCBs” (graphical abstract right).

Why this issue matters

In vitro and other non-animal methods are increasingly used in risk assessment, but many approaches were validated using single constituents with a limited range of physicochemical properties that did not challenge system stability. As a result, methodological modifications may be needed when testing difficult-to-test substances, including many UVCBs, which can be poorly soluble, (semi)volatile, and contain multiple constituents. These properties can make it challenging to establish and maintain relevant concentrations in common in vitro systems, causing losses to plastics, evaporation, and binding in media, and hence complicating test result interpretation.

What the paper achieved

This systematic review:

• maps the current use of hydrophobic, (semi)volatile chemicals and UVCBs in in vitro tests,
• summarizes strategies used for testing difficult-to-test substances and complex mixtures in vitro, including WAF/MAF approaches, passive dosing, and closed exposure systems,
• highlights practical considerations to improve reliability, emphasizing fit-for-purpose design and exposure verification.

Link to the publication: Wennberg et al. 2026. Critical Review of in Vitro Dosing Methods for Difficult-to-Test Substances and Hydrocarbon UVCBs. Environmental Toxicology and Chemistry. https://doi.org/10.1093/etojnl/vgag044

Learn more about the HESI Global UVCB Committee: https://hesiglobal.org/uvcb/