Evaluation of the utility of the Beta Human Liver Emulation System (BHLES) for CFSAN's regulatory toxicology program.

Microphysiological systems (MPS), such as organ-on-a-chip platforms, are an emerging alternative model that may be useful for predicting human physiology and/or toxicity. Due to the interest in these platforms, the Center for Food Safety and Applied Nutrition partnered with Emulate to evaluate the utility of the Beta Human Liver Emulation System (BHLES) for its regulatory science program. Using known hepatotoxic compounds (usnic acid, benzbromarone, tamoxifen, and acetaminophen) and compounds that have no reported human cases of liver toxicity (dimethyl sulfoxide, theophylline, and aminohippurate) the platform's performance was evaluated. Chemical toxicity was assessed by albumin secretion, urea and LDH release, nuclei number, mitochondrial membrane potential, and apoptosis. System/platform performance was evaluated in terms of sensitivity and specificity, power, and variability and repeatability. Chemical interactions with the Chip material were also assessed. Preliminary findings suggested that for the model test compounds selected, the BHLES accurately predicted toxicity, demonstrated high sensitivity and specificity, high power, and low variability. However, some compounds interacted with the Chip material indicating variable exposure levels that should be accounted for when planning experimentation. The details of the evaluation are presented herein.