Fluoride (F) widely exists in environment with a significant increase in body burden accumulation in recent years. Internal exposure to F due to diet including food, water, fluoride-containing dental products like toothpaste and fluoride supplements, is extensively researched. Additionally, industrial pollution and coal burning have also been reported to be major sources of internal F exposure, especially in China.

It is known that excessive fluoride intake over a long period of time may result in a serious public health problem called fluorosis. In addition to well-known effects of fluorine on skeleton and teeth, the neurotoxicity of F was also confirmed. Roholm et al found that exposure to fluoride can cause bad effect on the central nervous system in rats, generate significant reduction in myelinated nerve fibers, external granular layer in cerebellum, and increase neuronal apoptosis. In addition, alternations in the density of neurons and in the number of undifferentiated neurons were observed in the brains of fetuses therapeutically aborted in an area characterized by endemic fluorosis. It has been indicated that the severity of the adverse effects of fluoride on the behavior of rats is directly correlated to the concentrations of this ion in plasma and in specific regions of the brain. A growing number of epidemiological studies reported that the levels of mental work capacity and the Intelligence Quotient (IQ) for children who were born and raised in the areas with endemic fluorosis were found to be lower than normal.

F concentration in drinking water is long-term stable in years in a certain region. Once absorbed into the blood, fluoride readily distributes throughout the body, with the greatest amount retained in calcium-rich areas such as bone and teeth (dentine and enamel). In infants, about 80-90% of the absorbed fluoride is retained; the other is excreted primarily via the urine. Therefore, urine F and serum F concentrations as the internal exposure index can systematically reflect the burden of F exposure in drinking water. In this study, we measured children’s intelligence quotient IQ) using Combined Raven’s Test for Rural China (CRT-RC) and determined fluorine concentrations of serum and urine employing fluorine ion selective electrode, and investigated the correlations between the urine F and serum F concentrations and the children’s IQ.

Studies suggested that the neurotransmitter dopamine plays an important role in human cognition. Computational modeling studies indicated that dysfunction in dopamine systems accounts for abnormal cognitive control in the prefrontal cortex. Catechol Omethyltransferase (COMT) is the major mammalian enzyme involved in the metabolic degradation of released dopamine and accounts for more than 60% of the metabolic degradation of dopamine in the frontal cortex. It is therefore plausible that genetic factors that affect COMT function may significantly influence cognition through affecting dopaminergic function. The COMT gene contains a functional polymorphism that codes for a substitution of methionine (met) for valine (vai) at codon 158. The met allele is thermo labile and has one-fourth the enzymatic activity of the vai allele. Egan and his colleagues found that there was a relationship between the COMT vall58met polymorphism and cognitive function. However, the relationship between the COMT val158met polymorphism and cognitive function of children in fluoride area has not been reported.

At present, the study of biomarkers of children with mental retardation is rare. Studies have shown that thyroid hormone levels can be used as a sensitive indicator of detection of mental retardation. As direct executor of life function, proteins can directly reflect the physiological process relative to genes. Therefore, we can make use of the proteomics approach to study changes of certain protein or peptide level in the development process of fluorosis to find the abnormal expressed proteins so as to provide certain basis for identifying the biological markers of fluorosis children.