Development of Fluoride Toxicity including Cognitive Impairment with Reduced Iq: Pathophysiology, Interactions with Other Elements, and Predisposing and Protective Factors

The development of toxicity to the fluoride ion (F) may be complex and multifactorial with a number of pathophysiological pathways being possible, with the potential for interactions between toxins involving additivity, synergism, and antagonism, and with a number of other factors having predisposing and protective effects. In addition to cognitive impairment with a reduced intelligence quotient (IQ) in children developing through other mechanisms such as disturbed thyroid hormone metabolism and sonic hedgehog signalling, other pathophysiological factors such as reduced brain glucose uptake following a fluoride-induced reduction in insulin secretion may contribute. Environmental contamination with cadmium in a coal combustion fluorosis-affected rural area within China's Three Gorges region may contribute to the dental and skeletal health problems in the population and the possibility of interactions between Cd and F affecting cognitive functioning requires further investigation. The propensity for the development of toxicity to F may involve interactions with a number of other factors as well as the levels of F exposure.