Poly- and per-fluoroalkyl substances toxicity on skeletal and cognitive well-being: a comprehensive review

Poly- and per-fluoroalkyl substances (PFAS) are a large group of synthetic compounds having a wide array of use in consumer products and industries, such as fire suppressant foam, nonstick cookware, paper, water-proof textiles, surfactants, aeronautics, and cosmetics. This widespread distribution of PFAS, their capacity to accumulate in living organisms, and their harmful effects represent a rising concern for public health. A multitude of studies have presented information on exposure to PFAS and a broad spectrum of adverse health outcomes through animal models and observational studies. Here, we have reviewed various studies that are related to PFAS toxicity on bone and brain and its underlying mechanisms. PFAS have well-established toxicological effects on bone, such as reduced osteoblastic and increased osteoclastic activity, increased activation of peroxisome proliferator activated receptor-γ (PPAR-γ), and increased expression of WNT11. With respect to brain, PFAS have been linked with autism, somnolence, sleep disturbances, glioma, Alzheimer's, decreased cognition, increased expression of Glycogen Synthase β (GSK3β). Further research is required in several areas, such as age-specific toxicological effects of PFAS, impact of various other PFAS compounds beyond perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and involvement of peroxisome proliferator-activated receptors in PFAS-induced toxicity. Regarding brain toxicity, extensive research in adults is required as there is currently a relative scarcity of studies in this age group when compared to the available research conducted on children and older individuals.