Dose–effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children

Although a dose–effect relationship between water fluoride levels and damage to liver and kidney functions in animals has been reported, it was not demonstrated in humans. To evaluate the effects of drinking water fluoride levels on the liver and kidney functions in children with and without dental fluorosis, we identified 210 children who were divided into seven groups with 30 each based on different drinking water fluoride levels in the same residential area. We found that the fluoride levels in serum and urine of these children increased as the levels of drinking water fluoride increased. There were no significant differences in the levels of total protein (TP), albumin (ALB), aspartate transamine (AST), and alanine transamine (ALT) in serum among these groups. However, the activities of serum lactic dehydrogenase (LDH), urine N-acetyl-β-glucosaminidase (NAG), and urine γ-glutamyl transpeptidase (γ-GT) in children with dental fluorosis and having water fluoride of 2.15–2.96 mg/L and in children having water fluoride of 3.15–5.69 mg/L regardless of dental fluorosis were significantly higher than children exposed to water fluoride of 0.61–0.87 mg/L in a dose–response manner. In contrast to children with dental fluorosis and having water fluoride of 2.15–2.96 and 3.10–5.69 mg/L, serum LDH activity of children without dental fluorosis but exposed to the same levels of water fluoride as those with dental fluorosis were also markedly lower, but the activities of NAG and γ-GT in their urine were not. Therefore, our results suggest that drinking water fluoride levels over 2.0 mg/L can cause damage to liver and kidney functions in children and that the dental fluorosis was independent of damage to the liver but not the kidney. Further studies on the mechanisms and significance underlying damage to the liver without dental fluorosis in the exposed children are warranted.