Linear, short-chain polyfluorinated and perfluorinated alkyl compounds, often referred to as PFCs, have been in worldwide use as surfactants and polymer precursors for decades, and environmental dispersal of these highly persistent compounds represents a public health threat. Whereas ubiquitous low-level exposure to these compounds has been demonstrated in human populations from around the world, the exact mechanisms of toxicity and their toxic potency remain subject to investigation and scientific dispute. As with other environmental exposures, a major hurdle for gaining a better understanding of their human health impacts is the limited utility of cell culture and animal models serving as convenient, yet imperfect proxies to human physiology and disease. The present communication provides a brief overview of the current understanding of potential health effects of PFC exposure and examines how new toxicoproteomic methodologies can provide insight into the molecular mechanism of PFC exposure. Furthermore, we showcase an exemplary data set to illustrate how toxicoproteomic, population-wide studies might overcome limitations of animal models to more fully understand the metabolism and effects of PFCs and other environmental stressors where it matters most, in human populations experiencing real-world, chronic, low-level exposures.
Keywords: HNF4A; PFOA; PFOS; PPAR; exposure; infant health; proteomics.