Fluoride

Pursuant to 21 C.F.R. § 10.25(a)(2) and 21 C.F.R. § 10.30, the Fluoride Action Network and International Academy of Oral Medicine & Toxicology (collectively, “Petitioners”), respectfully submit this Petition to request that the Commissioner of the U.S. Food & Drug Administration (FDA) exercise its authority under the Food, Drug & Cosmetic Act to take action to ensure an expedited removal from the market of unapproved, unsafe, unnecessary, and ineffective sodium fluoride-containing drops, tablets, and lozenges sold for the intended purpose of caries prevention (i.e., “fluoride supplements”).

OBJECTIVE: To conduct a systematic review of randomised trials assessing the association between personal oral hygiene and dental caries in the absence of the confounding effects of fluoride.

Most of the studies included in this systematic review are more than 20 years old. As such, the reporting of the trials often lacked meth-odological detail necessary to produce high quality recommendations.  When new trials on fluoride mouthrinses for caries control are conducted, these should focus on direct comparisons between dif-ferent fluoride mouthrinse features or comparisons of fluoride rinses against other preventive strategies, such as tooth sealants. Since there is also little evidence related to adverse effects of flu-oride mouthrinses, additional studies to quantify and describe tooth staining, mucosal irritation, and acute toxicity are warranted.

The elevated fluoride from drinking water impacts on T3, T4 and TSH hormones. The aim was study impacts of drinking water fluoride on T3, T4 and TSH hormones inYGA (Yazd Greater Area). In this case- control study 198 cases and 213 controls were selected. Fluoride was determined by the SPADNS Colorimetric Method. T3, T4 and TSH hormones tested in the Yazd central laboratory by RIA (Radio Immuno Assay) method. The average amount of TSH and T3 hormones based on the levels of fluoride in two concentration levels 0-0.29 and 0.3-0.5 (mg/L) was statistically significant (P = 0.001 for controls and P = 0.001 for cases). In multivariate regression logistic analysis, independent variable associated with Hypothyroidism were: gender (odds ratio: 2.5, CI 95%: 1.6-3.9), family history of thyroid disease (odds ratio: 2.7, CI 95%: 1.6-4.6), exercise (odds ratio: 5.34, CI 95%: 3.2-9), Diabetes (odds ratio: 3.7, CI 95%: 1.7-8), Hypertension (odds ratio: 3.2, CI 95%: 1.3-8.2), water consumption (odds ratio: 4, CI 95%: 1.2-14). It was found that fluoride has impacts on TSH, T3 hormones even in the standard concentration of less than 0.5 mg/L. Application of standard household water purification devices was recommended for hypothyroidism.

Purpose: Excessive fluoride ingestion has been associated with dental fluorosis. The purpose of this study was to determine if there was a difference in dental fluorosis prevalence comparing National Health and Nutrition Examination Survey (NHANES) trend data for adolescents, aged 16 and 17 years, when compared to data collected in 2001-2002 to data from 2011-2012.Methods: The sample included 875 participants. Data analyses included Chi square tests and logistic regressions. The data were from a nationally representative survey by calibrated dental examiners using the modified Dean’s fluorosis classification system. The data analysis of the prevalence of fluorosis severity level was dichotomized to very mild/above vs. normal/questionable.Results: In 2001-2002, the weighted percentage prevalence of the denoted dental fluorosis categories were: 49.8% normal (i.e., unaffected), 20.5% questionable, and 29.7% very mild and above. In 2011-2012, the weighted percentage prevalence categories were: 31.2% normal, 7.5% questionable, and 61.3% very mild and above. When comparing years 2001-2002 with the years 2011-2012, the prevalence of very mild and above fluorosis increased by 31.6% (P <.0001) for the 2011-2012 group. In adjusted logistic regression, participants from the years 2011-2012 were more likely to have very mild and above dental fluorosis than participants in 2001-2002 as compared with normal/questionable fluorosis (Adjusted odds ratio= 3.85; 95% confidence interval= 2.20, 6.72; P <.0001).Conclusion: There was a difference of 31.6% in dental fluorosis prevalence between 2012-2011 when compared to data from 2002-2001 in adolescents aged 16 and 17 years. The continued increase in fluorosis rates in the U.S. indicates that additional measures need to be implemented to reduce its prevalence.

In this opinion article, FV Zohoori and A. Maguire highlight the importance of controlling
systemic fluoride intake from food and drink in early childhood to minimise risk of dental
fluorosis whilst maximizing caries prevention.

BACKGROUND:
Fluoride exposure has the potential to disrupt thyroid functioning, though adequate iodine intake may mitigate this effect. This is the first population-based study to examine the impact of chronic low-level fluoride exposure on thyroid function, while considering iodine status. The objective of this study was to determine whether urinary iodine status modifies the effect of fluoride exposure on thyroid stimulating hormone (TSH) levels.

METHODS:
This cross-sectional study utilized weighted population-based data from Cycle 3 (2012-2013) of the Canadian Health Measures Survey (CHMS). Information was collected via a home interview and a visit to a mobile examination centre. The weighted sample represented 6,914,124 adults in Canada aged 18-79 who were not taking any thyroid-related medication. Urinary fluoride concentrations were measured in spot samples using an ion selective electrode and adjusted for specific gravity (UFSG). Serum TSH levels provided a measure of thyroid function. Multivariable regression analyses examined the relationship between UFSG and TSH, controlling for covariates.

RESULTS:
Approximately 17.8% of participants fell in the moderately-to-severely iodine deficient range. The mean (SD) age of the sample was 46.5 (15.6) years and the median UFSG concentration was 0.74 mg/L. Among iodine deficient adults, a 1 mg/L increase in UFSG was associated with a 0.35 mIU/L increase in TSH [95% CI: 0.06, 0.64; p = 0.01, one-tailed].

CONCLUSIONS:
Adults living in Canada who have moderate-to-severe iodine deficiencies and higher levels of urinary fluoride may be at an increased risk for underactive thyroid gland activity.

Previous studies showed that prolonged exposure to fluoride (F-) and aluminum (Al3+) ions is associated with numerous diseases including neurological disorders. They don’t have any known biological function. But they can bind with proteins that interact with ions similar to them. Such unwanted interactions affect the normal biological function of the target proteins, as well as their downstream protein-protein interactions. Several studies show the detrimental effects posed by them including Alzheimer’s disease. However, their target proteins have never been reported. Here, we have screened for the human protein targets subjected to F- and Al3+ interactions by using data-driven prediction tools. We have identified 20 different proteins that directly bind with them (10 interact with fluoride and 10 with aluminum). In addition, protein-protein interaction has been explored to find the proteins that indirectly interact with F- and Al3+. We have found 86 indirect targets for F- and 90 for Al3+. Furthermore, 19 common protein targets have been identified, including proteins (9 out of 19) associated with neurodegenerative disorders. However, wet lab experiments are beyond our scopes to validate the binding networks. Additional studies must be warranted.

The goal of these statements is to provide the aforementioned stakeholders with a unified and authoritative voice on issuesrelated to dental, oral, and craniofacial health and research.AADR has a number of policy statements freely accessible online.

Introduction
This study’s purpose is to determine whether nonconsumption of tap water is associated with lower prevalence of elevated blood lead levels and higher prevalence of dental caries in children and adolescents.

Methods
Cross-sectional data from the National Health and Nutrition Examination Survey 2005–2014 recorded drinking water source (n=15,604) and blood lead levels (n=12,373) for participants aged 2–19 years, and dental caries experience for the 2011–2014 subset (n=5,677). The threshold for elevated blood lead level was ≥3 μg/dL. A binary outcome indicated presence or absence of dental caries experience. Multivariable generalized linear models estimated adjusted prevalence ratios with 95% confidence limits.

Results
In analysis conducted in 2017, 15% of children and adolescents did not drink tap water, 3% had elevated blood lead levels ≥3 μg/dL, and 50% had dental caries experience. Children and adolescents who did not drink water were less likely than tap water drinkers to have an elevated blood lead level (adjusted prevalence ratios=0.62, 95% confidence limits=0.42, 0.90). Nonconsumers of tap water were more likely to have dental caries (adjusted prevalence ratios=1.13, 95% confidence limits=1.03, 1.23). Results persisted after adjustment for other covariates and using a higher threshold for elevated blood lead level.

Conclusions
In this nationally representative U.S. survey, children and adolescents who did not drink tap water had lower prevalence of elevated blood lead levels and higher prevalence of dental caries than those who drank tap water.