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Present study was undertaken to investigate the toxic effect of sodium fluoride (NaF)– and fluoride (F)-contaminated ground water on reproductive performances of male rats. Healthy adult male rats were categorised into three groups, first group of rats were served as control, whereas second group of rats were orally intubated with NaF (10 mg/kgbw/1 ml/rat) and third group of rats were allowed to drink F-contaminated ground water (5 mg/L) through drinking water bottles for 52 days. Exposure of NaF- and F-contaminated ground water caused significant decline in sperm motility, serum concentration of testosterone, and increase in sperm abnormality compared with controls. Further, significant histological alterations characterized with shrunken seminiferous tubules and degeneration of different stages of spermatogonial cells were observed in rats treated with NaF- and F-contaminated ground water. After the confirmation of toxic effect of F, these NaF- and F-contaminated ground water–treated male rats were allowed to mate with proven fertile untreated female rats to study the reproductive performances of male rats. There was a decline in parturition index, fertility index of male and female, gestation index and number of pups delivered in NaF-treated male rats compared with controls. However, gestation index and number of pups delivered were declined in F-contaminated ground water–treated male rats compared with controls. These results clearly indicate that F exposure affected the reproductive performances of male rats. The present study further revealed the fact that F-induced decline in testosterone levels, reduced sperm motility, and loss of spermatogonial cells affected the reproductive performances of male rats.

Background The application of 38 % silver diamine fluoride (SDF) has been shown to be effective in arresting early childhood caries (ECC). Since SDF is not available in certain countries, some dentists use adjunctive application of 25 % silver nitrate (AgNO 3 ) and 5 % sodium fluoride (NaF) to arrest ECC. This randomised controlled trial will systematically compare the efficacy of a 25 % AgNO 3 solution followed by 5 % NaF varnish with that of a 38 % SDF solution in arresting ECC when applied at half-yearly intervals over a 30-month period. Methods/Design This study is a randomised, double-blinded, non-inferiority clinical trial. The hypothesis tested is that adjunctive application of 25 % AgNO 3 followed by 5 % NaF is at least not appreciably worse than a 38 % SDF in arresting ECC. Approximately 3100 kindergarten children aged 3–4 years will be screened and at least 1070 children with caries will be recruited. This sample size is sufficient for an appropriate statistical analysis (power at 90 % ( β  = 0.10) with a 2-sided type-I error of α  = 0.05), allowing for an overall 20 % drop-out rate. The children will be randomly allocated into 2 groups to treat their caries over a 30-month period: Group A – biannual adjunctive application of a 25 % AgNO 3 solution and a 5 % NaF varnish, and Group B – biannual adjunctive application of a 38 % SDF solution followed by a placebo varnish. Clinical examinations will be conducted at 6-month intervals. Primary outcome measured is the number of active caries surfaces which are arrested. Information on confounding factors such as oral hygiene habits will be collected through a parental questionnaire. Discussion We expect that adjunctive application of 25 % AgNO 3 solution and 5 % NaF varnish and of 38 % SDF solution can both effectively arrest ECC. Lower concentrations of silver and fluoride are contained in 25 % AgNO 3 and 5 % NaF, respectively, than in 38 % SDF; therefore, AgNO 3 /NaF are more favourable for use in young children. Because its use for caries management is painless, simple, low-cost, and approved in many countries, AgNO 3 /NaF could be widely recommended and promoted as an alternative treatment to conventional invasive management of ECC. Trial registration ClinicalTrials.gov: NCT02019160 . Date of registration: 11 December 2013.

Fluorine is one of the trace elements necessary for health. It has many physiological functions, and participates in normal metabolism. However, fluorine has paradoxical effects on the body. Many studies have shown that tissues and organs of humans and animals appear to suffer different degrees of damage after long‐term direct or indirect exposure to more fluoride than required to meet the physiological demand. Although the aetiology of endemic fluorosis is clear, its specific pathogenesis is inconclusive. In the past 5 years, many researchers have conducted in‐depth studies into the pathogenesis of endemic fluorosis. Research in the areas of fluoride‐induced stress pathways, signalling pathways and apoptosis has provided further extensive knowledge at the molecular and genetic level. In this article, we summarize the main results.

Despite WHO standards, waterborne diseases among the human being are rising alarmingly. It is known that the prolong exposure to contaminated water has major impact on public health. The effect of chemical contaminations in drinking water on human being is found to be chronic rather than acute and hence can be defined “consumption of contaminated drinking water could be a silent killer”. As the WHO recommended water quality standards are only for individual element and synergic effects of trace metals and anions have not been considered, investigation of synergic effects of trace metals and anions and their effect on human being is of prime important research. By an animal trial, we investigated the synergic effect(s) of heavy metals, aluminium, arsenic, fluoride and hardness in drinking water on kidney tissues of mice. Our investigation strongly suggests existing of a synergic effect especially among Cd, F and hardness of water which could lead to severe kidney damage in mice, even at WHO maximum recommended levels. Hence, the synergic effect(s) of trace metals, fluoride and hardness present in drinking water should be investigated meticulously when stipulating the water quality at WHO maximum recommended levels.

This study compared the staining potential of two experimental amine fluoride/stannous fluoride mouth rinses (A and B), a phenolic/essential oil rinse (C) and a negative control, water, rinse (D). The study was a single centre, randomized, single-blind, four treatment crossover study design among healthy participants. Prior to each study period, participants received a dental prophylaxis. On the Monday of each period, subjects suspended oral hygiene, and under supervision, rinsed with the allocated mouth rinse immediately followed by a warm black tea solution at hourly intervals eight times a day for 4 days. On Friday, the area and intensity of staining on the teeth, the primary outcome measure and dorsum of tongue were assessed. This regimen was repeated for all the three subsequent treatment periods. Rinse B produced less stain than rinse A, but the difference was not significant ( p  = 0.20). Rinse B produced significantly more stain than rinse C ( p  < 0.05) and D ( p  < 0.001). For tongue staining, rinse B produced significantly more staining than D ( p  < 0.01) but not A or C. Overall, all test rinses produced more staining than placebo with an overall pattern for more staining with stannous formulations. Individuals using stannous or phenolic/essential oil mouth rinse formulations should be advised of the possible staining side effect and that this can be easily removed by a professional dental cleaning.

Environmental risk factors for dementia are poorly understood. Aluminium and fluorine in drinking water have been linked with dementia but uncertainties remain about this relationship. In the largest longitudinal study in this context, we set out to explore the individual effect of aluminium and fluoride in drinking water on dementia risk and, as fluorine can increase absorption of aluminium, we also examine any synergistic influence on dementia. We used Cox models to investigate the association between mean aluminium and fluoride levels in drinking water at their residential location (collected 2005-2012 by the Drinking Water Quality Regulator for Scotland) with dementia in members of the Scottish Mental Survey 1932 cohort who were alive in 2005. A total of 1972 out of 6990 individuals developed dementia by the linkage date in 2012. Dementia risk was raised with increasing mean aluminium levels in women (hazard ratio per s.d. increase 1.09, 95% CI 1.03-1.15, P < 0.001) and men (1.12, 95% CI 1.03-1.21, P = 0.004). A dose-response pattern of association was observed between mean fluoride levels and dementia in women (1.34, 95% CI 1.28-1.41, P < 0.001) and men (1.30, 95% CI 1.22-1.39, P < 0.001), with dementia risk more than doubled in the highest quartile compared with the lowest. There was no statistical interaction between aluminium and fluoride levels in relation with dementia. Higher levels of aluminium and fluoride were related to dementia risk in a population of men and women who consumed relatively low drinking-water levels of both.

Different studies have suggested that fluoride is related to neurological disorders in children and adolescents, but clinical evidences of which neurological parameters associated to fluoride exposure are, in fact, still controversial. In this way, this systematic review and meta-analysis aimed to show if there is an association between fluoride exposure from different sources, doses and neurological disorders. Terms related to “ Humans ”; “ Central nervous system ”; “ Fluorides ”; and “ Neurologic manifestations ” were searched in a systematic way on PubMed , Scopus , Web of Science , Lilacs , Cochrane and Google Scholar. All studies performed on humans exposed to fluoride were included on the final assessment. A meta-analysis was then performed and the quality level of evidence was performed using the GRADE approach. Our search retrieved 4,024 studies, among which 27 fulfilled the eligibility criteria. The main source of fluoride was naturally fluoridated water. Twenty-six studies showed alterations related to Intelligence Quotient (IQ) while only one has evaluated headache, insomnia, lethargy, polydipsia and polyuria. Ten studies were included on the meta-analysis, which showed IQ impairment only for individuals under high fluoride exposure considering the World Health Organization criteria, without evidences of association between low levels and any neurological disorder. However, the high heterogeneity observed compromise the final conclusions obtained by the quantitative analyses regarding such high levels. Furthermore, this association was classified as very low-level evidence. At this time, the current evidence does not allow us to state that fluoride is associated with neurological damage, indicating the need for new epidemiological studies that could provide further evidences regarding this possible association.

Fluorine is widely dispersed in nature and has multiple physiological functions. Although it is usually regarded as an essential trace element for humans, this view is not held universally. Moreover, chronic fluorosis, mainly characterized by skeletal fluorosis, can be induced by long-term excessive fluoride consumption. High concentrations of fluoride in the environment and drinking water are major causes, and patients with skeletal fluorosis mainly present with symptoms of osteosclerosis, osteochondrosis, osteoporosis, and degenerative changes in joint cartilage. Etiologies for skeletal fluorosis have been established, but the specific pathogenesis is inconclusive. Currently, active osteogenesis and accelerated bone turnover are considered critical processes in the progression of skeletal fluorosis. In recent years, researchers have conducted extensive studies in fields of signaling pathways (Wnt/β-catenin, Notch, PI3K/Akt/mTOR, Hedgehog, parathyroid hormone, and insulin signaling pathways), stress pathways (oxidative stress and endoplasmic reticulum stress pathways), epigenetics (DNA methylation and non-coding RNAs), and their inter-regulation involved in the pathogenesis of skeletal fluorosis. In this review, we summarised and analyzed relevant findings to provide a basis for comprehensive understandings of the pathogenesis of skeletal fluorosis and hopefully propose more effective prevention and therapeutic strategies.

Over the past 75 years, health authorities have declared that community water fluoridation—a practice that reaches over 400 million worldwide—is safe. Yet, studies conducted in North America examining the safety of fluoride exposure in pregnancy were nonexistent. When a Canadian study reported that higher fluoride exposure in pregnant women was associated with lower IQ scores in young children, critics attacked the methodology of the study and discounted the significance of the results. Health authorities continued to conclude that fluoride is unequivocally safe, despite four well-conducted studies over the last 3 years consistently linking fluoride exposure in pregnancy with adverse neurodevelopmental effects in offspring. We describe the challenges of conducting fluoride research and the overt cognitive biases we have witnessed in the polarized fluoride debate. The tendency to ignore new evidence that does not conform to widespread beliefs impedes the response to early warnings about fluoride as a potential developmental neurotoxin. Evolving evidence should inspire scientists and health authorities to re-evaluate claims about the safety of fluoride, especially for the fetus and infant for whom there is no benefit.

We recently completed a comprehensive systematic review of the literature on fluoride exposure and neurodevelopment and cognition, resulting in two publications. The 2024 National Toxicology Program Monograph concluded-with -that higher fluoride exposure is associated with lower IQ in children. The 2025 meta‑analysis, published in , quantitatively synthesized over 70 epidemiological studies and likewise reported an inverse association between fluoride exposure and children's IQ. This inverse association persisted when analyses were restricted to the best evidence, the high‑quality studies, and was consistent across subgroups defined by sex, age, country, outcome assessment method, timing of exposure, and exposure matrix (e.g., urine or drinking water). Notably, among the high‑quality evidence, inverse associations were still observed at fluoride exposure levels below 1.5 mg/L, based on both urinary and drinking‑water measurements. These publications have received considerable public and media attention, prompted healthy scientific discourse, and have been cited by public health decision‑makers. Many scientific comments were carefully considered and resolved during development and peer review, which contributed to the rigor of the final documents. However, some recurrent critiques continue to be raised. This viewpoint provides a high‑level summary of these key critiques and corresponding responses to help the public, media, and the scientific community better understand the strength and implications of the scientific evidence on fluoride exposures and neurodevelopment and cognition.