Fluoride and human health: Systematic appraisal of sources, exposures, metabolism, and toxicity

Fluoride (F−) originating from many natural geologic sources and anthropogenic activities has imposed a substantial environmental health risk. More than 200 million people from more than 35 nations are at risk of fluorosis, thus increasing the global attention paid to F− research. The present study reviews the mechanisms of F− ingestion from possible sources and exposures, correlating possible health effects by extensively surveying the literature. The relationship between F− levels in drinking water and dental and skeletal fluorosis has been studied for decades. However, several alternative routes of exposure, such as food and other supplements, influence fluorosis incidence and hinder benchmarking of fluorosis levels with F− concentrations in drinking water. Deposition of F− in developing teeth, accompanied by the loss of matrix protein, leads to deformities in tooth enamel and dentin. Skeletal fluorosis results from the strong and irreversible inclusion of F− in the deeper parts of bone and causes increased bone mass and density along with enlarged joints. This review article also describes extensive in vivo or in vitro studies of F− ingestion in laboratory animals and the correlation of F− exposure with several health effects.