Fluoride

BACKGROUND:
A panel of experts convened by the American Dental Association (ADA) Council on Scientific Affairs presents evidence-based clinical recommendations regarding professionally applied and prescription-strength, home-use topical fluoride agents for caries prevention. These recommendations are an update of the 2006 ADA recommendations regarding professionally applied topical fluoride and were developed by using a new process that includes conducting a systematic review of primary studies.

TYPES OF STUDIES REVIEWED:
The authors conducted a search of MEDLINE and the Cochrane Library for clinical trials of professionally applied and prescription-strength topical fluoride agents–including mouthrinses, varnishes, gels, foams and pastes–with caries increment outcomes published in English through October 2012.

RESULTS:
The panel included 71 trials from 82 articles in its review and assessed the efficacy of various topical fluoride caries-preventive agents. The panel makes recommendations for further research.

PRACTICAL IMPLICATIONS:
The panel recommends the following for people at risk of developing dental caries: 2.26 percent fluoride varnish or 1.23 percent fluoride (acidulated phosphate fluoride) gel, or a prescription-strength, home-use 0.05 percent fluoride gel or paste or 0.09 percent fluoride mouthrinse for patients 6 years or older. Only 2.26 percent fluoride varnish is recommended for children younger than 6 years. The strengths of the recommendations for the recommended products varied from “in favor” to “expert opinion for.” As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner’s professional judgment and the patient’s needs and preferences.

In this paper we estimate the comparative overall cost for U.S. society between using cheaper industrial grade HFSA as the principal fluoridating agent versus using more costly pharmaceutical grade (U.S. Pharmacopeia – USP) NaF. USP NaF is used in toothpaste. HFSA, a liquid, contains significant amounts of arsenic (As). HFSA and NaSF have been shown to leach lead (Pb) from water delivery plumbing, while NaF has been shown not to do so. The U.S. Environmental Protection Agency’s (EPA) health-based drinking water stan-dards for As and Pb are zero. Our focus was on comparing the social costs associated with the difference in numbers of cancer cases arising from As during use of HFSA as fluoridating agent versus substitution of USP grade NaF. We calculated the amount of As delivered to fluoridated water systems using each agent, and used EPA Unit Risk values for As to estimate the number of lung and bladder cancer cases associated with each. We used cost of cancer cases published by EPA to estimate cost of treating lung and bladder cancer cases. Com-mercial prices of HFSA and USP NaF were used to compare costs of using each to fluoridate. We then compared the total cost to our society for the use of HFSA versus USP NaF as fluoridating agent. The U.S. could save $1 billion to more than $5 billion/year by using USP NaF in place of HFSA while simultaneously mitigating the pain and suffering of citizens that result from use of the technical grade fluoridating agents.

“Sabour and Ghorbani’s comments about the reported mean difference in IQ (intelligence quotient) scores reported in our article (Choi et al. 2012) suggest a misunderstanding of the scale unit we used and the public health significance of even a small decrease in the average IQ associated with exposure. We appreciate this opportunity to clarify the factual information about the reported IQ measure.  The standardized weighted mean difference (SMD) in IQ score between exposed and reference populations was –0.45 (95% confidence interval: –0.56, –0.35) using a random-effects model (Choi et al. 2012). We used the SMD because the studies we included used different scales to measure the general intelligence. The SMD is a weighted mean difference standardized across studies, giving the average difference in standard deviations for the measure of that outcome. For commonly used IQ scores with a mean of 100 and an SD of 15, 0.45 SDs is equivalent to 6.75 points (rounded to 7 points). As research on other neurotoxicants has shown, a shift to the left of IQ distributions in a population will have substantial impacts, especially among those in the high and low ranges of the IQ distribution.”

Fractional fluoride retention is important during the early years of life when considering the risk of development of dental fluorosis. This study aimed to measure fractional fluoride retention in young children. The objectives were to investigate the relationships between fractional fluoride retention and total daily fluoride intake, age, and body mass index (BMI). Twenty-nine healthy children, up to 4 yr of age, participated; 14 lived in a fluoridated area (0.64 μg ml(-1) of fluoride in drinking water) and 15 lived in a non-fluoridated area (0.04 μg ml(-1) of fluoride in drinking water). The total daily fluoride intake of each child was calculated from the daily dietary fluoride intake and toothpaste ingestion (if fluoride toothpaste was used). Total daily fluoride excretion was measured by collecting voided urine and faeces over a 24-h period, and fractional fluoride retention was calculated by dividing the amount of fluoride retained in the body (total daily fluoride intake minus total daily fluoride excretion) by the total daily fluoride intake. Nine children were excluded from data analysis because of suspected invalid samples. Mean (range) fractional fluoride retention for the remaining 20 children was 0.61 (0.06-0.98). There were no statistically significant correlations between fractional fluoride retention and either age or BMI. However, fractional fluoride retention was correlated with total daily fluoride intake: fractional fluoride retention = 1 – exp (-C × total daily fluoride intake), where C = 28.75 (95% CI = 19.75-37.75). The wide variation in fluoride retention in young children could have important implications when recommendations for fluoride use are being considered.

Fluoride (F) is ubiquitous natural substance and widespread industrial pollutant. Although low fluoride concentrations are beneficial for normal tooth and bone development, acute or chronic exposure to high fluoride doses results in adverse health effects. The molecular mechanisms underlying fluoride toxicity are different by nature. Fluoride is able to stimulate G-proteins with subsequent activation of downstream signal transduction pathways such as PKA-, PKC-, PI3-kinase-, Ca2+-, and MAPK-dependent systems. G-protein-independent routes include tyrosine phosphorylation and protein phosphatase inhibition. Along with other toxic effects, fluoride was shown to induce oxidative stress leading to excessive generation of ROS, lipid peroxidation, decrease in the GSH/GSSH ratio, and alterations in activities of antioxidant enzymes, as well as to inhibit glycolysis thus causing the depletion of cellular ATP and disturbances in cellular metabolism. Fluoride triggers the disruption of mitochondria outer membrane and release of cytochrome c into cytosol, what activates caspases-9 and -3 (intrinsic) apoptotic pathway. Extrinsic (death receptor) Fas/FasL-caspase-8 and -3 pathway was also described to be implicated in fluoride-induced apoptosis. Fluoride decreases the ratio of antiapoptotic/proapoptotic Bcl-2 family proteins and upregulates the expression of p53 protein. Finally, fluoride changes the expression profile of apoptosis-related genes and causes endoplasmic reticulum stress leading to inhibition of protein synthesis.

With this edition of The Handbook of Environmental Chemistry “Polyfluorinated Chemicals and Transformation Products” we aim to give an overview of the recent state of the art. Polyfluorinated chemicals (PFC) are widespread substances with effective and measurable effects to environment and economy. Topics, such as synthesis and application, analysis and degradation as well as environmental aspects, food and toxicity are spotlighted.

CONTEXT:
Fluoroquinolones are commonly prescribed classes of antibiotics. Despite numerous case reports of ocular toxicity, a pharmacoepidemiological study of their ocular safety, particularly retinal detachment, has not been performed.

OBJECTIVE:
To examine the association between use of oral fluoroquinolones and the risk of developing a retinal detachment.

DESIGN, SETTING, AND PATIENTS:
Nested case-control study of a cohort of patients in British Columbia, Canada, who had visited an ophthalmologist between January 2000 and December 2007. Retinal detachment cases were defined as a procedure code for retinal repair surgery within 14 days of a physician service code. Ten controls were selected for each case using risk-set sampling, matching on age and the month and year of cohort entry.

MAIN OUTCOME MEASURE:
The association between retinal detachment and current, recent, or past use of an oral fluoroquinolone.

RESULTS:
From a cohort of 989,591 patients, 4384 cases of retinal detachment and 43,840 controls were identified. Current use of fluoroquinolones was associated with a higher risk of developing a retinal detachment (3.3% of cases vs 0.6% of controls; adjusted rate ratio [ARR], 4.50 [95% CI, 3.56-5.70]). Neither recent use (0.3% of cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45-1.87]) nor past use (6.6% of cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89-1.19]) was associated with a retinal detachment. The absolute increase in the risk of a retinal detachment was 4 per 10,000 person-years (number needed to harm = 2500 computed for any use of fluoroquinolones). There was no evidence of an association between development of a retinal detachment and β-lactam antibiotics (ARR, 0.74 [95% CI, 0.35-1.57]) or short-acting β-agonists (ARR, 0.95 [95% CI, 0.68-1.33]).

CONCLUSION:
Patients taking oral fluoroquinolones were at a higher risk of developing a retinal detachment compared with nonusers, although the absolute risk for this condition was small.

“Background: Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children’s neurodevelopment.

Objective: We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development.

Methods: We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg’s funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies.

Results: The standardized weighted mean difference in IQ score between exposed and reference populations was –0.45 (95% confidence interval: –0.56, –0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease.

Conclusions: The results support the possibility of an adverse effect of high fluoride exposure on children’s neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.”

“One of the sad stories about what was considered to be a successful prevention of tooth decay is represented by fluoride supplementation of water and toothpastes. But even today, without knowing all the scientific reliable proofs, all the pieces of a very large puzzle, this action has many (especially in developing countries) promoters. That’s why we considered that a well-documented review in this domain would be of large interest, especially because the deleterious effects are many, accompanied by a large number of threats for the health, and the benefits are lacking.”

Perfluorinated compounds (PFCs) form a diverse group of chemicals with surface-active properties manufactured for over 50 years. In recent years, a number of studies have reported the ubiquitous distribution of PFCs in human tissues and wildlife. Although the relative importance of the routes of human exposure to these compounds is not well established yet, it has been suggested that food intake and packaging, water, house dust, and airborne are all potentially significant sources. However, dietary intake is probably the main route of exposure to these compounds, including perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), the most extensively investigated PFCs. This paper reviews the state of the science regarding the concentrations of PFCs in foodstuffs, human dietary exposure to these compounds and their health risks. The influence of processing, cooking and packaging on the PFCs levels in food is also discussed. Because of the rather limited information about human dietary exposure, studies to determine exposure to PFCs through the diet for the general population of a number of countries are clearly necessary. The correlation of PFCs body burdens and dietary intake of PFCs should be also established.