Zuo H, Chen L, Kong M, Qiu L, Lü P, Wu P, Chen K. Toxic effects of fluoride on organisms. Life sciences. 2018 Apr 1;198:18-24. doi: 10.1016/j.lfs.2018.02.001.
Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead to mitochondrial damage, endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity.
Perera T, Ranasinghe S, Alles N, Waduge R. Effect of fluoride on major organs with the different time of exposure in rats. Environmental health and preventive medicine. 2018 May 16;23(1):17. doi: 10.1186/s12199-018-0707-2.
BACKGROUND: High fluoride levels in drinking water in relation to the prevalence of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka were investigated using rats as an experimental model.
METHOD: The effects of fluoride after oral administration of Sodium fluoride (NaF) at levels of 0, 0.5, 5 and 20 ppm F– were evaluated in adult male Wistar rats. Thirty-six rats were randomly divided into 4 groups (n = 9), namely, control, test I, II, and III. Control group was given daily 1 ml/rat of distilled water and test groups I, II, and III were treated 1 ml/rat of NaF doses of 0.5, 5, and 20 ppm, respectively, by using a stomach tube. Three rats from the control group and each experimental group were sacrificed after 15, 30, and 60 days following treatment. Serological and histopathological investigations were carried out using blood, kidney, and liver.
RESULTS: No significant differences were observed in body weight gain and relative organ weights of the liver and kidney in fluoride-treated groups compared to control group. After 60 days of fluoride administration, group I showed a mild portal inflammation with lytic necrosis while multiple areas of focal necrosis and various degrees of portal inflammation were observed in groups II and III. This was further confirmed by increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. As compared with control and other treated groups, group III showed a significantly higher serum AST activity (p < 0.05) and ALT activity (p < 0.05) after 60 days and ALP activity with a significant difference (p < 0.05) after 15, 30, and 60 days. The renal histological analysis showed normal histological features in all groups with the elevated serum creatinine levels in group III compared to those in the groups I and II (p < 0.05) after 60 days. Significantly elevated serum fluoride levels were observed in group II of 30 and 60 days and group III after 15, 30, and 60 days with respective to control groups (p < 0.05).
CONCLUSION: Taken together, these findings indicate that there can be some alterations in liver enzyme activities at early stages of fluoride intoxication followed by renal damage.
Nakamoto T, Rawls HR. Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life. The Journal of clinical pediatric dentistry. 2018 May 15. doi: 10.17796/1053-4625-42.5.1.
Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and other applications. In the current review, we have concentrated primarily on early-life exposure to fluoride and how it may affect the various organs. The most recent controversial aspects of fluoride are related to toxicity of the developing brain and how it may possibly result in the decrease of intelligence quotient (IQ), autism, and calcification of the pineal gland. In addition, it has been reported to have possible effects on bone and thyroid glands. If nutritional stress is applied during a critical period of growth and development, the organ(s) and/or body will never recover once they pass through the critical period. For example, if animals are force-fed during experiments, they will simply get fat but never reach the normal size. Although early-life fluoride exposure causing fluorosis is well reported in the literature, the dental profession considers it primarily as an esthetic rather than a serious systemic problem. In the current review, we wanted to raise the possibility of future disease as a result of early-life exposure to fluoride. It is not currently known how fluoride will become a cause of future disease. Studies of other nutritional factors have shown that the effects of early nutritional stress are a cause of disease in later life.
Sayanthooran S, Gunerathne L, Abeysekera TDJ, Magana-Arachchi DN. Transcriptome analysis supports viral infection and fluoride toxicity as contributors to chronic kidney disease of unknown etiology (CKDu) in Sri Lanka. International urology and nephrology. 2018 May 28. doi: 10.1007/s11255-018-1892-z.
PURPOSE: Chronic kidney disease of unknown etiology (CKDu), having epidemic characteristics, is being diagnosed increasingly in certain tropical regions of the world, mainly Latin America and Sri Lanka. They have been observed primarily in farming communities and current hypotheses point toward many environmental and occupational triggers. CKDu does not have common etiologies of chronic kidney disease (CKD) such as hypertension, diabetes, or autoimmune disease. We aimed to understand the molecular processes underlying CKDu in Sri Lanka using transcriptome analysis.
METHODS: RNA extracted from whole blood was reverse transcribed and used for microarray analysis using the Human HT-12 v.4 array (Illumina). Pathway analysis was carried out using ingenuity pathway analysis (IPA-Qiagen). Microarray results were validated using real-time PCR of five selected genes.
RESULTS: Pathways related to innate immune response, including interferon signaling, inflammasome signaling and TREM1 signaling had the most significant positive activation z scores, where as EIF2 signaling and mTOR signaling had the most significant negative activation z scores. Pathways previously linked to fluoride toxicity; G-protein activation, Cdc42 signaling, Rac signaling and RhoA signaling were activated in CKDu patients. The most significantly activated biological functions were cell death, cell movement and antimicrobial response. Significant toxicological functions were mitochondrial dysfunction, oxidative stress and apoptosis.
CONCLUSIONS: Based on the molecular pathway analysis in CKDu patients and review of literature, viral infections and fluoride toxicity appear to be contributing to the molecular mechanisms underlying CKDu.
Patil MM, Lakhkar BB, Patil SS. Curse of Fluorosis. Indian J Pediatr. 2018 Jan 3. doi: 10.1007/s12098-017-2574-z.
Fluoride was identified to have caries preventive properties and was widely used for fluoridation of water since 1940, especially in developed countries. After this there was sudden increase in the use of fluorides in food items and in oral medicinal products like toothpastes and mouth washes. Inadvertent use of above has lead to increase in fluorosis as a public health problem. In many places high fluorides are naturally present in earth crust leading to high water fluoride content increasing the risk of fluorosis. Maintaining a fine balance of fluorides in the body is mandatory for exploiting its advantages. World Health Organization (WHO) has fixed permissible limit of fluorides in water to 1.5 mg/L as a preventive step to contain fluorosis. Fluorosis has three clinical components: Dental, Skeletal and Non-Skeletal Fluorosis. It occurs with increasing level of fluorides in the body. Acute toxicity due to fluorides is also known and occurs as a result of sudden exposure to high levels of fluorides, usually by ingestion. Once fluorosis occurs it is irreversible without any cure. Only symptomatic and supportive management is possible. Hence prevention is the mainstay of management. Prevention is by using alternative sources of water or its de-fluoridation. National Program for Prevention and Control of Fluorosis (NPPCF) was launched in 2008-9 to identify areas with high fluoride content of water, manage the water bodies, screen schools and community for fluorosis and comprehensive management of cases. Improving quality of drinking water as per standards and improving nutritional status of children are also important components of prevention of fluorosis.
Choi AL, Zhang Y, Sun G, Bellinger DC, Wang K, Yang XJ, Li JS, Zheng Q, Fu Y, Grandjean P. Association of lifetime exposure to fluoride and cognitive functions in Chinese children: a pilot study. Neurotoxicol Teratol. 2015 Jan-Feb;47:96-101. doi: 10.1016/j.ntt.2014.11.001. Erratum in Neurotoxicol Teratol. 2015 Sep-Oct;51():89.
BACKGROUND: A systematic review and meta-analysis of published studies on developmental fluoride neurotoxicity support the hypothesis that exposure to elevated concentrations of fluoride in water is neurotoxic during development.
METHODS: We carried out a pilot study of 51 first-grade children in southern Sichuan, China, using the fluoride concentration in morning urine after an exposure-free night; fluoride in well-water source; and dental fluorosis status as indices of past fluoride exposure. We administered a battery of age-appropriate, relatively culture-independent tests that reflect different functional domains: the Wide Range Assessment of Memory and Learning (WRAML), Wechsler Intelligence Scale for Children-Revised (WISC-IV) digit span and block design; finger tapping and grooved pegboard. Confounder-adjusted associations between exposure indicators and test scores were assessed using multiple regression models.
RESULTS: Dental fluorosis score was the exposure indicator that had the strongest association with the outcome deficits, and the WISC-IV digit span subtest appeared to be the most sensitive outcome, where moderate and severe fluorosis was associated with a digit span total score difference of -4.28 (95% CI -8.22, -0.33) and backward score with -2.13 (95% CI -4.24, -0.02).
CONCLUSIONS: This pilot study in a community with stable lifetime fluoride exposures supports the notion that fluoride in drinking water may produce developmental neurotoxicity, and that the dose-dependence underlying this relationship needs to be characterized in detail.
Waugh DT, Potter W, Limeback H, Godfrey M. Risk Assessment of Fluoride Intake from Tea in the Republic of Ireland and its Implications for Public Health and Water Fluoridation. International journal of environmental research and public health. 2016 Feb 26;13(3). pii: E259. doi: 10.3390/ijerph13030259.
The Republic of Ireland (RoI) is the only European Country with a mandatory national legislation requiring artificial fluoridation of drinking water and has the highest per capita consumption of black tea in the world. Tea is a hyperaccumulator of fluoride and chronic fluoride intake is associated with multiple negative health outcomes. In this study, fifty four brands of the commercially available black tea bag products were purchased and the fluoride level in tea infusions tested by an ion-selective electrode method. The fluoride content in all brands tested ranged from 1.6 to 6.1 mg/L, with a mean value of 3.3 mg/L. According to our risk assessment it is evident that the general population in the RoI is at a high risk of chronic fluoride exposure and associated adverse health effects based on established reference values. We conclude that the culture of habitual tea drinking in the RoI indicates that the total cumulative dietary fluoride intake in the general population could readily exceed the levels known to cause chronic fluoride intoxication. Evidence suggests that excessive fluoride intake may be contributing to a wide range of adverse health effects. Therefore from a public health perspective, it would seem prudent and sensible that risk reduction measures be implemented to reduce the total body burden of fluoride in the population.