Elsevier

Environmental Research

Volume 103, Issue 1, January 2007, Pages 112-116
Environmental Research

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

https://doi.org/10.1016/j.envres.2006.05.008Get rights and content

Abstract

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.

Introduction

Fluoride is present in varying amount in the air, water, and food, and high concentration of fluoride has toxic effects in both humans and animals, causing disorders such as endemic fluorosis and industrial fluorosis. Endemic fluorosis is related to the high concentration of fluoride present in the drinking water (Li and Cao, 1994), while industrial fluorosis is mainly due to air pollution of fluoride in the working environment (Grandjean et al., 1985; Czerwinski et al., 1988). Fluorosis causes damage to many of animal and human organs (Wei, 1979; Li and Cao, 1994; Finkelman et al., 1999), predominately the skeletal systems and teeth as well as the structure and functions of the non-skeletal systems, such as brain, liver, kidney, and spinal cord (Guan et al., 1998; Dote et al., 2000; Wang et al., 2004).

As a site of very active metabolism, the liver is especially susceptible to fluoride toxicity (Wang and Li, 2002; Guo et al., 2003). The main pathway of fluoride elimination is via the kidney. Because 50–80% of absorbed fluoride is eliminated by the kidney, the kidney is also sensitive to fluoride intoxication (Guan et al., 2000; Guo et al., 1989). Some animal and epidemiological studies showed that exposure to excessive fluoride could induce damage to the liver and kidney (Wang et al., 1993; Michael et al., 1996; Shivashankara et al., 2000; Wang et al., 2000). Furthermore, some animal experiments revealed that a significant dose–effect relationship was detected between water fluoride levels and damage to the liver and kidney functions (Liu et al., 1994; Dote et al., 2000; Guan et al., 2000; Shashi and Thapar, 2000). Surprisingly, few studies have examined the effects of fluoride on the functions of human liver and kidney and the possible dose–effect relationship between fluoride levels and damage to human liver and kidney functions. In the present study, we analyzed some sensitive indexes that reflect liver and kidney functions in children with and without dental fluorosis (we called these asymptomatics exposed to high levels of water fluoride as with high-loaded fluoride) in residential areas with different levels of drinking water fluoride and to explore the dose–effect relationship between drinking water fluoride levels and damage to human liver and kidney functions. We also observed the difference in the levels of damage to liver and kidney functions in children with and without dental fluorosis in the residential area having the same level of drinking water fluoride.

Section snippets

Sample collection

According to the fluoride concentration of the drinking water and dental fluorosis status, which was assessed by Dean's index, a total of 210 children (age range from 10 to 12) were selected from four areas in Anyang and Neihuang County (Henan Province, China) where the levels of drinking water fluoride were different, i.e., 0.76 mg/L (0.61–0.87 mg/L), 1.47 mg/L (1.1–2.0 mg/L), 2.58 mg/L (2.15–2.96 mg/L), and 4.51 mg/L (3.1–5.69 mg/L), respectively. The fluoride concentrations in the samples of dinking

The fluoride contents in urine and serum

As shown in Table 1, the fluoride levels in the serum and urine were significantly higher in children without and with dental fluorosis in residential areas with high drinking-water fluoride than in the controls. Furthermore, the fluoride levels in serum and urine increased gradually as drinking-water fluoride levels increased. However, no differences in serum fluoride levels were detected between children with and without dental fluorosis in the same area, but in the area with drinking-water

Discussion

In the present study, we found that fluoride levels in urine and serum of children with and without dental fluorosis from high drinking-water fluoride areas were statistically significantly higher than that of the control children exposed to low drinking-water fluoride in a dose–response manner. Earlier studies about the relationship of the levels of serum fluoride and the degree of fluorosis have produced inconsistent results (Song et al., 1995; Zhou et al., 1997). Song et al. (1995) found

Acknowledgments

The authors would like to express their sincere thanks to Dr. Qingyi Wei for his critical review of the manuscript. This work was supported by grants from the National Nature Science Foundation of China (No: 30271155, and 30371250), and the China National Key Basic Research and Development Program (No. 2002CB512908).

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