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ICCVAM Biennial Report 2020-2021

Biennial Progress Report 2020-2021 Interagency Coordinating Committee on the Validation of Alternative Methods

In Vitro Dosimetry Analyses for Acrolein Exposure in Human Cells

Establishing accurate dosimetry is important for assessing the toxicity of xenobiotics as well as for comparing responses between different test systems. Scientists at the FDA Center for Tobacco Products and the FDA National Center for Toxicological Research used acrolein as a model toxicant and defined the concentration–response relationships of the key adverse responses in both normal human bronchial epithelial cells and human pulmonary carcinoma cells (Xiong et al. 2021). The researchers developed a new method for indirectly estimating the intracellular uptake of acrolein based on the chemical’s key alkylation reactions. Responses, including protein carbonylation, glutathione depletion, and glutathione–acrolein adduct formation, were all linearly correlated with acrolein uptake in both cell types. The study demonstrated that normal human bronchial epithelial cells were more sensitive to acrolein exposure than the pulmonary carcinoma cells and provided mechanistic information about acrolein-induced cytotoxicity. The dosimetric analysis presented in this study may provide useful information for computational modeling and risk assessment of acrolein using different test systems.