| Background:Fluorine is widely found in nature and is one of the13most abundant natural elements in the Earth’s surface. Although scientists are still not sure the fluoride whether a vital role in human health, but many people believe that a small amount of fluoride in the diet helps to prevent tooth decay and strengthen bones. On the other hand, long-term intake of high doses of fluoride can produce adverse effects on human health, including dental fluorosis and skeletal fluorosis, increased risk of fractures, resulting in declining birth rate, increased urinary calculi (kidney stones), resulting in hypothyroidism and reduce children’s intelligence. Endemic fluorosis is widely distributed in the world which includes more than50countries and regions of five continents. China is one of most serious endemic fluorosis in the world. According to the ways of fluoride intake, endemic fluorosis in China can be divided into several types:drinking water type, coal burning pollution type, drinking tea type and mixed type, and the most serious one is drinking water type fluorosis, followed by coal burning type which can lead to dental and skeletal fluorosis epidemic. Most of fluorosis endemic areas in southern China are drinking water type and Guangdong is the most serious one confirmed in the1980s. The province totally has396endemic villages located in115towns of37counties of14cities with an endemic population of502,400. Shantou, a city in eastern Guangdong province, is the most serious city in14endemic cities with an endemic population of216,100. The dental fluorosis prevalence in the children aged8-15in Shantou endemic areas was62.01%. The procedures to treat fluorosis in Guangdong Province is to provide low fluoride public water for the residents in the endemic villages and which has been conducted since the late1980s and the remarkable results have been achieved. Until2003, the province has finished changing the water in all endemic areas and93.3%of the population has got the benefits, and the average prevalence rate of dental fluorosis has fell to41.5%from61.12%.However, even though the content of fluoride in the water has been reduced, the effects on the human being remain a lot of unknown elements since the fluoride in the water has a dual effect on human health. For instance, below what dose or higher than what dose the fluoride in the water is harmful to health? What is the acceptable dose? What are the benchmark doses to beneficially or harmfully affect human health? How to assess the health risk for the population in the endemic fluorosis areas? High fluoride areas of fluoride exposure groups, especially groups of children and how to assess the health risks? What dosage of fluoride is safety in the Changed water, and how to determine this dose etc.. The aim of this paper is to create an assessing method to evaluate the children’s health risk who explored to the high water fluoride environment but have had water changed for different years, as well as to recommend a safety dose for the local government based on the calculation of bench mark doses.Objective:based on the study on the years of the children’s exposure, the duration of water changed and different specific effects responded to fluoride exposures, to determine the benchmark doses of the specific effects of different fluoride exposures, to seek the changing rules and dose-response relationship ofthe specific effective criteria related to different water change years and children’s urinary fluoride contents, to establish the children’s health risk evaluation model and to provide the scientific basis for decision making to set the fluorine exposure limits and improve the children’s health in the endemic fluorosis areas.Methods:Four endemic fluorosis villages were randomly selected from63endemic fluorosis village of Chaonan county, Shantou city as well as a non-endemic fluorosis village and all of the children aged6-12were chosen for the examination of dental fluorosis, dental caries and600were selected for determines of fluoride contents in urine and serum osteocalcin, calcitonin, alkaline phosphates’ content and bone mineral density. According to the test results of the above indicators, children’s health risk assessment was conducted based on the Risk Assessment Guide revised in2001by the U.S. Environmental Protection Agency. The evaluation steps included identification of hazards, the dose-response relationship, evaluation of exposure assessment, and risk analysis. Software SPSS16.0and BMDS were used for statistics Including the identification of hazards by using Logistic regression analysis to analyze the correlation of fluoride exposure and the prevalence of various indicators(P<0.05showes statistically significant); using BMDS software to evaluate dose-response relationship and draw the dose-response curve between urine fluoride and indicators and calculate the reference dose, and the benchmark dose lower limit; average exposure was assessed to describe the dose of fluoride exposure, with a ceiling of90%of each indicator to determine the scope of the exception indicators; Logistic regression was used to analyze the relationship between exposure and abnormal; risk determination and risk scope were determined based on the benchmark dose lower limit.Results:Fluoride contents in villages A, B, C, D before water changed were5.51mg/1,2.17mg/1,3.99mg/1and3.31mg/1. They all came down to0.11mg/1after water changed, consistent with the control village. The average of the children’s urine fluoride in village E (control) was0.480mg/1, and those in A, B, C, D villages were0.62mg/1,0.51mg/1,0.36mg/1and0.27mg/1after water changed. The difference was statistically significant between the observed villages and the control one (χ2=127.915, P<0.001). The averaged children’s urine fluoride in village A was higher than control, while the C and D Villages were lower than the control village. The children serum osteocalcin levels were significantly different among the years of water change(F=14.465, P<0.001), village B which was14years of water changed and control Village E were lower than the others. There are statistical differences between the levels of serum calcitonin(F=48.959, P<0.001), village B and C were lower than other villages but no difference between B and C. Differences between children serum alkaline phosphates’activity were statistically significant (F=9.831, P<0.001), Village C and D were lower than Village E. Children’s bone mineral densities were also different(F=3.781,P=0.005), A Village and C village were higher than B village.The dental fluorosis prevalence rate in the observed villages was76.99%before water change. After the water changes, all the observed villages except A have decreased to30%(below this value can be judged as a non-fluorine area). Based on the control Village E, the Logistic regression showes that the OR value of Village A was7.71(χ2=212.02, P<0.001), and no statistically significant OR values of the other villages. The dental caries prevalence rates in five villages were higher than30%. E village’s caries prevalence was49.7%. Compared with E village of control, the Logistic regression analysis showed that the caries prevalence of villages A, B, C, D ware31.97%(OR=0.48, χ2=73.62, P<0.001),65.0%(OR=1.88, χ2=21.38, P<0.001),56.3%(OR=1.31, χ2=10.81, P<0.001), and45.2%(OR=0.83, χ2=3.40, P<0.001) respectively. All of the villages’osteocalcin, alkaline phosphates’and bone mineral density abnormal rates were not higher than the control village, but calcitonin anomalies in village A was higher than the control Village E,(OR=6.39,χ2=27.14, P<0.001).With the increase in urine fluoride, dental fluorosis prevalence as well as OR values gradually increased. The urine fluoride content in the0.00-group had the highest caries prevalence of53.9%; The0.37-group had the lowest prevalence of dental caries of39.8%; The change showed a U-shaped trend. Osteocalcin, alkaline phosphates, bone mineral density anomaly rates were not different among the different urine fluoride groups. The calcitonin abnormal rate showed an upward trend with the increase of urinary fluoride contents. Compared to the urine fluoride content of0.0～group, the0.6～group’s abnormal osteocalcin OR was2.35(χ2=4.02, P=0.045), and the0.9～group’s OR was2.78(χ2=4.90, P=0.027).The dose-response model of urinary fluoride and dental fluorosis selected Logistic model, with a benchmark dose BMD=0.857mg/1, BMDL (benchmark dose lower limit)=0.720mg/1. The dose-response relationship between the children’s urinary fluoride and dental caries selected the Multistage model, the down trend curve of BMD and BMDL values were1.095and0.898mg/1, and the up trend curve of BMD and BMDL values were0.275and0.124mg/1respectively. Logistic regression model was selected to calculate the dose-response relationship of urinary fluoride and osteocalcin and BMD=0.975mg/1, BMDL=0.622mg/1. The calcitonin abnormal dose-response relationship model calculated Quantal-linear model:the BMD=0.636mg/1, BMDL=0.383mg/1. ALP dose-response relationship model was a Logistic regression model and the BMD=2.299mg/1, BMDL=0.837mg/1. Abnormal urinary fluoride and bone mineral density’s dose-response relationship model chosen the log-logistic regression model, the BMD was0.941mg/1, and the BMDL was0.811mg/1.The attributable risk (ARP) of dental fluorosis in the village with water change for six years was the lowest0.41; and the attributable risks for those with water change for14years,15years and17years were0.91,0.92and0.96. Compared with the lower limits for the safe dose range of each effect indicators and calculated OR value exceeded the safe dose range:OR values for dental fluorosis, osteocalcin, and calcitonin were2.415,1.945and1.761. Dental caries, alkaline phosphates, bone mineral density OR values were not statistically significant. The total value of risk calculated based on the combination of weight of quality of life and abnormal rate of the indicators showed an upward trend:total risk increases with the increasing of urinary fluoride content.Conclusion:1. The content of the fluoride in the drinking water in the water-changed villages meets the national health standards for drinking water (1.0mg/1or less).2. When the water has been changed for more than six years, the observed village children’s urinary fluoride, dental fluorosis prevalence and health effect indicators have reached the levels of non-fluorine village.3. There are dose-response relationship between children’s urinary fluoride and dental fluorosis, caries prevalence and four fluoride-induced bone damage indicators (BPG, CT, ALP, and bone mineral density). Urinary fluoride and dental caries shows a U-shaped curve relationship.4.Through the dose-response relationship building between urinary fluoride and dental fluorosis, dental caries and four fluoride-induced bone injury indicators (BPG, CT, ALP, and bone mineral density), the BMD values for the above indicators were:0.857mg/1,1.095mg/1(caries upper limit) and0.275mg/1(caries lower limit value),0.975mg/1,0.636mg/1,2.299mg/1and0.941mg/1; BMDL value were:0.720mg/1,0.898mg/1(caries upper limit) and0.124mg/1(caries limit)0.622mg/1,0.383mg/1,0.837mg/1and0.811mg/1.5. The urinary fluoride benchmark dose lower limit for each indicator can be used as a biological limit for the local areas.6. In the observed villages with water change, the risk of dental caries in village B and C was higher than other villages. |
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