Dose–effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children☆
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).
References (26)
- et al.
Influence of chronic fluorosis on membrane lipids in rat brain
Neurotoxicol. Teratol.
(1998) - et al.
Effect of long term fluoride exposure on lipid composition in rat liver
Toxicology
(2000) - et al.
The effect of Pycnogenol on fluoride induced rat kidney lysosomal damage in vitro
Phytother. Res.
(2004) - et al.
Bone and joint pathology in fluoride-exposed workers
Arch. Environ. Health
(1988) - et al.
Toxicokinetics of intravenous fluoride in rats with kidney damage caused by high-dose fluoride exposure
Int. Arch. Occup. Environ. Health
(2000) - et al.
Health impacts of domestic coal use in China
Proc. Natl. Acad. Sci. USA
(1999) - et al.
Mortality and cancer morbidity after heavy occupational fluoride exposure
Am. J. Epidemiol.
(1985) - et al.
Changed cellular membrane lipid composition and lipid peroxidation of kidney in rats with chronic fluorosis
Arch. Toxicol.
(2000) - et al.
Study of kidney function in residents of some endemic fluorosis epidemic area
Chin. J. Health Toxicol.
(1989) - et al.
Effects of oxidative stress on rat's hepatic damage caused by subchronic fluorosis
Chin. J. Public Health
(2003)
Medical aspects of excessive fluoride in a water supply
Pub. Health Rep.
Recent studies on endemic fluorosis in China
Fluoride
Analyses of blood chemistry and electrolytes of human exposure to fluoride in drinking water
Chin. J. Pub. Health
Cited by (222)
Longitudinal associations between early-life fluoride exposures and cardiometabolic outcomes in school-aged children
2024, Environment InternationalSize-tunable graphitized carbon spheres for water defluoridation
2023, Colloids and Surfaces A: Physicochemical and Engineering AspectsInflammation- and cancer-related microRNAs in rat renal cortex after subchronic exposure to fluoride
2023, Chemico-Biological InteractionsBinding interactions and sensing applications of chromone derived Schiff base chemosensors via absorption and emission studies: A comprehensive review
2022, Inorganic Chemistry CommunicationsDevelopment of a fluorescent strategy for quantification of fluoride ions in foods and toothpaste
2022, Chemical Engineering Journal
- ☆
In this research, we selected 210 children from Henan Province to investigate the relationship between drinking water fluoride and damage to liver and kidney functions in children with and without dental fluorosis. The study with children's participation were conducted in accordance with national and institutional guidelines for the protection of human subjects and animal welfare.