AN EVALUATION OF TOXICITY IN FLUOROTELOMER-BASED AQUEOUS FILM-FORMING FOAM (AFFF) EXPOSED HUMAN LIVER CELLS

Aqueous film-forming foams (AFFF) are highly effective firefighting substances that are used to extinguish flammable liquid fires and prevent their reignition. AFFF are typically formed by combining hydrocarbon foaming agents and fluorinated surfactants, which provide foam formulations with the required properties necessary for forming a vapor barrier between the fuel and atmospheric oxygen to suppress the flame. However, AFFF are a cause for concern because of the fluorinated constituents present within the mixtures. The fluorinated compounds, known as per- and polyfluoroalkyl substances (PFAS), possess high chemical stability and environmental recalcitrance, granting them the appellation “forever chemicals.” Presently, over 14,000 PFAS have been identified and many of these chemicals are utilized in consumer products worldwide. PFAS have been associated with adverse health effects such as cancer, reproductive impairment, developmental defects, impaired immune function, thyroid disease, and liver disease in humans and toxicological models. Perfluorooctane sulfonate (PFOS) was used extensively in historical formulations of AFFF and is ubiquitous in the environment due to ground and surface water contamination from AFFF emissions and other sources. Due to the potent toxicological profiles of PFOS and a similar C8 carboxylate, perfluorooctanoic acid (PFOA), both PFAS have been phased out of use and replaced with alternative PFAS that were believed to be less toxic. This dissertation research characterizes the content of new-generation, fluorotelomer-containing AFFF through high-resolution mass spectrometry and total organic fluorine (TOF) analysis. The toxicities and bioactivities of each detectable constituent were assessed through viability, lipid accumulation, and bioaccumulation measurements in human liver cells (HepaRG). These analyses revealed toxicological similarities between alternative PFAS, such as 6:2 fluorotelomer sulfonate (6:2 FTSA) with previously used C8 PFAS. Furthermore, high-throughput transcriptomic assays were performed using the TempO-Seq S1500+ platform to observe modulations of hepatic receptors, primarily of the peroxisome proliferating-activated receptor-alpha (PPARα) and constitutive androstane receptor (CAR). Benchmark concentration (BMC) calculations enabled the estimation of liver injury potential for each test substance. Biological response similarity analysis using hierarchical clustering for the identified transcriptomic pathways revealed similarities among PFOS, 6:2 FTSA and other legacy PFAS, imparting important insights of chemical similarity and enhancing our understanding of fluorotelomer AFFF toxicity.