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SUMMARY Most currently marketed fluoride varnishes (FVs) have not been evaluated for their effectiveness in preventing dental caries. The objective of this study was to investigate the anticaries efficacy, measured as fluoride release into artificial saliva (AS); change in surface microhardness of early enamel caries lesions; and enamel fluoride uptake (EFU) of 14 commercially available FVs and two control groups. Bovine enamel specimens (5×5 mm) were prepared and assigned to 18 groups (n=12). Early caries lesions were created in the specimens and characterized using Vickers microhardness (VHNlesion). FV was applied to each group of specimens. Immediately afterward, specimens were incubated in 4 mL of AS for 18 hours, which were collected and renewed every hour for the first six hours. AS samples were analyzed for fluoride using an ion-specific electrode. Specimens were then brushed for 20 seconds with toothpaste slurry and subjected to pH cycling consisting of a four-hour/day acid challenge and one-minute treatments with 1100 ppm F dentifrice for five days. Microhardness was measured following pH cycling (VHNpost). EFU was determined using microbiopsy. Acid resistance (eight-hour demin challenge) was performed after pH cycling, and microhardness was measured (VHNart) and compared with baseline values to test the FV impact after pH cycling. One-way analysis of variance was used for data analysis (α=0.05). FVs differed in their release characteristics (mean ± SD ranged from 14.97 ± 2.38 μg/mL to 0.50 ± 0.15 μg/mL), rehardening capability (mean ± SD ranged from 24.3 ± 15.1 to 11.7 ± 12.7), and ability to deliver fluoride to demineralized lesions (mean ± SD ranged from 3303 ± 789 μg/cm3 to 707 ± 238 μg/cm3). Statistically significant but weak linear associations were found between ΔVHN(post – lesion), EFU, and fluoride release (correlations 0.21-0.36). The results of this study demonstrated that differences in FV composition can affect their efficacy in in vitro conditions.

We evaluated if the low resistance of fluorotic enamel to demineralization could be overcome by fluoride dentifrice (FD) treatment. Paired enamel slabs of sound and fluorotic enamel (n = 20/group) from human teeth presenting Thylstrup and Fejerskov index (TF) scores from 0 to 4 were obtained. Half of the anatomic surface of the enamel slabs was isolated and used as a control (baseline) regarding enamel mineralization and fluoride concentration. The slabs were submitted to a pH-cycling model simulating a high cariogenic challenge, and 2×/day they were treated with placebo dentifrice (PD) or FD (1,100 µg F/g, as NaF). After 10 days, the slabs were cut into two halves. Enamel demineralization was evaluated by cross-sectional microhardness in one half, and the fluoride formed (FF) concentration was determined in the other half. For statistical analysis, the data on net demineralization area (ΔΔS) and FF (µg F/g) were grouped into TF0, TF1–2, and TF3–4, and analyzed by two-way ANOVA followed by Tukey’s test (α = 5%). The factors studied were TF (0, 1–2, and 3–4) and dentifrice treatment (PD or FD). The effect of the factors was statistically significant for ΔΔS and FF (p < 0.05). In the PD group, the following pattern for ΔΔS was observed: TF3–4 > TF1–2 > TF0 (p < 0.05); however, the groups did not differ (p > 0.05) when FD was used. Regarding FF, the groups treated with PD did not differ (p > 0.05), but the greatest (p < 0.05) FF concentration was found in group TF3–4 treated with FD. These findings suggest that the higher susceptibility of fluorotic enamel to demineralization lesions is decreased by the use of FD.

Objective : Fluoride exposure >1.5 mg/L from water has been associated with adverse pregnancy and birth outcomes. Little is known, however, about the effect of fluoride at levels consistent with water fluoridation (i.e., 0.7 mg/L) on pregnancy and birth outcomes. We examined the relationship between maternal fluoride exposure, fertility, and birth outcomes in a Canadian pregnancy cohort living in areas where municipal drinking water fluoride concentrations ranged from 0.04 to 0.87 mg/L. Methods : Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, we estimated fluoride exposure during pregnancy using three different metrics: 1) maternal urinary fluoride concentrations standardized for specific gravity (MUFSG) and averaged across all three trimesters (N = 1566), 2) water fluoride concentration (N = 1370), and 3) fluoride intake based on self-reported consumption of water, coffee, and tea, adjusted for body weight (N = 1192). Data on fertility, birth weight, gestational age, preterm birth, and small-for-gestational age (SGA) were assessed. We used multiple linear regression to examine associations between fluoride exposure, birth weight and gestational age, and logistic regression to examine associations with fertility, preterm birth, and SGA, adjusted for relevant covariates. Results : Median (IQR) MUFSG was 0.50 (0.33-0.76) mg/L, median water fluoride was 0.52 (0.17-0.64) mg/L, and median fluoride intake was 0.008 (0.003-0.013) mg/kg/day. MUFSG, water fluoride concentrations, and fluoride intake were not significantly associated with fertility, birth weight, gestational age, preterm birth, or SGA. Fetal sex did not modify any of the associations. Conclusion : Fluoride exposure during pregnancy was not associated with fertility or birth outcomes in this Canadian cohort.

Objectives To compare three children's sodium fluoride toothpastes to placebo with respect to enamel remineralisation potential, enamel fluoride uptake and net acid resistance using an in situ palatal caries model in children aged 11–14 years following a single brushing. Design This was a randomised, single blind (laboratory analyst), single-centre, four-treatment, crossover study with a 7-day washout period between treatments. The treatments were 1,426 ppm fluoride, 1,000 ppm fluoride, 500 ppm fluoride and 0 ppm fluoride (placebo) toothpaste (NaF/silica). A custom made in situ palatal appliance was used by each subject in all treatment periods. At each of the four treatment visits subjects wore the appliance containing four partially demineralised human enamel specimens for 5 minutes and then brushed their teeth using a standardised procedure for 60 seconds under supervision using 1.0 g (±0.1 g) of their assigned toothpaste. After 4 hours the appliance was removed and enamel specimen recovered. This process was repeated until all subjects completed all four study treatment visits. Recovered enamel specimens were analysed for per cent surface microhardness recovery (%SMHR; Knoop) and enamel fluoride uptake (EFU; microdrill biopsy). Subsequently, specimens were demineralised in vitro to determine their % net acid resistance (%NAR; Knoop). Results All three fluoride toothpastes demonstrated significantly greater %SMHR, EFU and %NAR compared with 0 ppm F toothpaste. The model demonstrated a dose response over the range 0 to 1,426 ppm fluoride for %SMHR, EFU and %NAR. There was no significant difference between 500 ppm F and 1,000 ppm F for %SMHR and between 1,000 ppm F and 1,426 ppm F for %SMHR, EFU and %NAR. Conclusions The present in situ study demonstrated that the children's fluoride toothpastes tested are capable of delivering cariostatic amounts of fluoride to early caries lesions following a single brushing.

Objectives To compare the effect of 40 seconds versus 2 minutes brushing on saliva and dental biofilm fluid fluoride in children ages 4–5 years over 1 hour. Design This was a single-blind, cross-over, randomised, two-period clinical study in healthy children. Three days before the start of each treatment subjects received a thorough brushing and then refrained from all oral hygiene procedures. At treatment visits, after collecting baseline biofilm and saliva samples, staff brushed the occlusal surfaces of the subject's posterior teeth with a pea-sized amount (0.25 g) of NaF/silica toothpaste for the randomised time. Samples were taken at 5 minutes, 15 minutes, 30 minutes and 60 minutes after brushing and analysed for fluoride using a microanalytical methodology. There was a minimum 4-day washout period between treatments. Results Log changes from baseline biofilm fluid and saliva fluoride were statistically significant (P

BACKGROUND: Recent studies have reported an inverse association between fluoride exposure and IQ in children, but most were ecological in design. Few involved personal measures of exposure or adjus...

BackgroundPrevious studies have shown a correlation between fluoride concentrations in urine and community water fluoride concentrations. However, there are no studies of the relationship between community water fluoridation, urine, serum, and amniotic fluid fluoride concentrations in pregnant women in the US. The aim of this study was to determine the relationship between maternal urine fluoride (MUF), maternal urine fluoride adjusted for specific gravity (MUFSG), maternal serum fluoride (MSF), amniotic fluid fluoride (AFF) concentrations during pregnancy, and community water fluoridation in Northern California.MethodsArchived samples of urine, serum and amniotic fluid collected from second trimester pregnant women in Northern California from 47 different communities in Northern California and one from Montana (n = 48), were analyzed for fluoride using an ion specific electrode following acid microdiffusion. Women’s addresses were matched to publicly reported water fluoride concentrations. We examined whether fluoride concentrations in biospecimens differed by fluoridation status of the community water, and determined the association between water fluoride concentrations and biospecimen fluoride concentrations using linear regression models adjusted for maternal age, smoking, Body Mass Index (BMI), race/ethnicity, and gestational age at sample collection.ResultsFluoride concentrations in the community water supplies ranged from 0.02 to 1.00 mg/L. MUF, MSF , and AFF concentrations were significantly higher in pregnant women living in communities adhering to the U.S. recommended water fluoride concentration (0.7 mg/L), as compared with communities with less than 0.7 mg/L fluoride in drinking water. When adjusted for maternal age, smoking status, BMI, race/ethnicity, and gestational age at sample collection, a 0.1 mg/L increase in community water fluoride concentration was positively associated with higher concentrations of MUF (B = 0.052, 95% CI:0.019,0.085), MUFSG(B = 0.028, 95% CI: -0.006, 0.062), MSF (B = 0.001, 95% CI: 0.000, 0.003) and AFF (B = 0.001, 95% CI: 0.000, 0.002).ConclusionsWe found universal exposure to fluoride in pregnant women and to the fetus via the amniotic fluid. Fluoride concentrations in urine, serum, and amniotic fluid from women were positively correlated to public records of community water fluoridation. Community water fluoridation remains a major source of fluoride exposure for pregnant women living in Northern California.

Objectives This study aimed to calculate the fluoride concentrations of commonly consumed foods and beverages for 2-years-old children utilizing market basket information for the US Midwest region. Methods Total Diet Study food lists were cross-referenced with National Health and Nutrition Examination Survey—What We Eat in America data to determine the foods and beverages to be included. Fluoride concentrations were determined using a modification of the hexamethyldisiloxane microdiffusion technique. Fluoride concentrations were summarized for each of the food categories. Daily dietary fluoride intake was estimated using a simulation analysis. Results Food and beverage fluoride concentrations varied widely, ranging from nondetectable for some oils and dairy products to more than 3.0 μgF/g food for some processed meats, fish and fruits. The estimated mean (±SD) daily dietary fluoride intake, excluding dentifrice and supplements, was 412±114 μgF/d. The estimated average ingestion for a 2-years-old weighing 12.24 kg was 0.034±0.009 mg/kg/d. A diet based on foods and beverages in the fifth percentile of fluoride intake distribution for an average child would result in 247 μgF/d or 0.020 mg/kg/d, while a diet with foods and beverages in the 95th percentile would result in a total intake of 622 μgF/d or 0.051 mg/kg/d. Conclusions The fluoride concentrations of foods and beverages vary widely, and, if items in the 95th percentile of fluoride intake distribution are ingested, children could consume more fluoride than the recommended 0.05 mg/kg/d. Fluoride intake calculated in this study was higher than historically reported dietary levels.

PurposeThe Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother–child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes.Participantsn=1643 mother–child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico.Findings to dateMaternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling.Future plansAs the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures.Trial registration numberNCT00558623.

Background: Sources of fluoride exposure for Mexicans include foods, beverages, fluoridated salt, and naturally fluoridated water. There are no available data describing fluoride content of foods and beverages consumed in Mexico. Objective: To measure the content of fluoride in foods and beverages typically consumed and to compare their content to that of those from the United States and the United Kingdom. Methods: Foods and beverages reported as part of the Mexican Health and Nutrition Survey (n = 182) were purchased in the largest supermarket chains and local markets in Mexico City. Samples were analyzed for fluoride, at least in duplicate, using a modification of the hexamethyldisiloxane microdiffusion method. Value contents were compared to those from the US Department of Agriculture and UK fluoride content tables. Results: The food groups with the lowest and highest fluoride content were eggs (2.32 µg/100 g) and seafood (371 µg/100 g), respectively. When estimating the amount of fluoride per portion size, the lowest content corresponded to eggs and the highest to fast foods. Meats and sausages, cereals, fast food, sweets and cakes, fruits, dairy products, legumes, and seafood from Mexico presented higher fluoride contents than similar foods from the United States or the United Kingdom. Drinks and eggs from the United States exhibited the highest contents, while this was the case for pasta, soups, and vegetables from the United Kingdom. Conclusion: The majority of items analyzed contained higher fluoride contents than their US and UK counterparts. Data generated provide the first and largest table on fluoride content, which will be useful for future comparisons and estimations.

Objectives Enamel fluorosis is a hypomineralization caused by chronic exposure to high levels of fluoride during tooth development. Previous research on the relationship between enamel fluoride content and fluorosis severity has been equivocal. The current study aimed at comparing visually and histologically assessed fluorosis severity with enamel fluoride content. Methods Extracted teeth ( n = 112) were visually examined using the Thylstrup and Fejerskov Index for fluorosis. Eruption status of each tooth was noted. Teeth were cut into 100 μm slices to assess histological changes with polarized light microscopy. Teeth were categorized as sound, mild, moderate, or severe fluorosis, visually and histologically. They were cut into squares (2 × 2 mm) for the determination of fluoride content (microbiopsy) at depths of 30, 60 and 90 μm from the external surface. Results Erupted teeth with severe fluorosis had significantly greater mean fluoride content at 30, 60 and 90 μm than sound teeth. Unerupted teeth with mild, moderate and severe fluorosis had significantly greater mean fluoride content than sound teeth at 30 μm; unerupted teeth with mild and severe fluorosis had significantly greater mean fluoride content than sound teeth at 60 μm, while only unerupted teeth severe fluorosis had significantly greater mean fluoride content than sound teeth at 90 μm. Conclusions Both erupted and unerupted severely fluorosed teeth presented higher mean enamel fluoride content than sound teeth. Clinical significance Data on fluoride content in enamel will further our understanding of its biological characteristics which play a role in the management of hard tissue diseases and conditions.

The aim was to compare potential methods for fluoride analysis in microlitre-volume plasma samples containing nano-gram amounts of fluoride. Methods: A group of 4 laboratories analysed a set of standardised biological samples as well as plasma to determine fluoride concentration using 3 methods. In Phase-1, fluoride analysis was carried out using the established hexamethyldisiloxane (HMDS)-diffusion method (1 mL-aliquot/analysis) to obtain preliminary measurement of agreement between the laboratories. In Phase-2, the laboratories analysed the same samples using a micro-diffusion method and known-addition technique with 200 µL-aliquot/analysis. Coefficients of Variation (CVs) and intra-class correlation coefficients (ICCs) were estimated using analysis of variance to evaluate the amount of variation within- and between-laboratories. Based on the results of the Phase-2 analysis, 20 human plasma samples were analysed and compared using the HMDS-diffusion method and known-addition technique in Phase-3. Results: Comparison of Phase-1 results showed no statistically significant difference among the laboratories for the overall data set. The mean between- and within-laboratory CVs and ICCs were < 0.13 and ≥0.99, respectively, indicating very low variability and excellent reliability. In Phase-2, the overall results for between-laboratory variability showed a poor CV (1.16) and ICC (0.44) for the micro-diffusion method, whereas with the known-addition technique the corresponding values were 0.49 and 0.83. Phase-3 results showed no statistically significant difference in fluoride concentrations of the plasma samples measured with HMDS-diffusion method and known- addition technique, with a mean (SE) difference of 0.002 (0.003) µg/mL. In conclusion, the known-addition technique could be a suitable alternative for the measurement of fluoride in plasma with microlitre-volume samples.

The purpose of this study was to investigate the effect of five commercially available fluoride varnishes (FV) on caries lesions. Ninety bovine enamel specimens were assigned to five varnish groups (n = 18). Early caries lesions were created in the specimens and characterized using Vickers surface microhardness number (VHN). FV was applied to each group of specimens. Immediately afterwards, 7.5 ml of artificial saliva (AS) were pipetted over each group of specimens, collected and renewed every 15 min for 6 h. AS samples were analyzed for fluoride using an ion-specific electrode. Enamel fluoride uptake (EFU) was determined using the acid etch technique. Each group was then subjected to a pH cycling regimen for 5 days after which VHN was determined again. One-way analysis of variance (ANOVA) was used for data analysis. FVs differed in their rehardening capability (highest mean value was for Enamel Pro = 32.3 ± 5.8 and lowest mean value was for Vanish = 18.9 ± 11.3). No significant difference in EFU was found among groups. Total fluoride release over 6 h was in the order of MI Varnish (303 μg/ml) > Enamel Pro (217 μg/ml) > Flor-Opal (153 μg/ml) > PreviDent(84 μg/ml) > Vanish(28 μg/ml). ΔVHN and fluoride release characteristics differ among FV products. These differences may be attributed to the different compositions and physical properties of the tested FV. Fundamental, comparable research on FV and how different formulations affect early caries lesion rehardening, fluoride release into saliva, and uptake by teeth is scarce.

Objective The objective was to evaluate the ability of fluoride in a conventional, non-specialised sodium fluoride–silica dentifrice to promote tooth remineralisation and enamel fluoride uptake (EFU), and assess the resistance of the newly formed mineral to attack by dietary acid, across the concentration range used in mass-market dentifrices. Methods Subjects wore a palatal appliance containing eight polished bovine enamel specimens, each including an early erosive lesion. In a randomised full-crossover sequence, 62 healthy subjects were treated with dentifrices containing four different fluoride concentrations: no fluoride; 250 ppm, 1150 ppm and 1426 ppm fluoride. At each treatment visit, under supervision, subjects brushed with 1.5 g dentifrice and rinsed once while wearing the appliance; the appliance was removed after a 4-h remineralisation period and effects on the enamel specimens determined. The primary efficacy variable was surface microhardness recovery (SMHR); others included EFU, relative erosion resistance (RER) and comparative erosion resistance. Results Highly significant linear and, with the exception of SMHR, quadratic dose–response relationships were observed between all efficacy variables and fluoride concentration. For SMHR, EFU and RER, values for the different fluoride concentrations were statistically resolved from one another, with the exception of the two highest fluoride concentrations. The degree of remineralisation and the acid resistance of enamel after treatment were closely related to EFU. Conclusion After a single brushing, conventional non-specialised sodium fluoride–silica dentifrices promoted remineralisation of early enamel lesions, and imparted increased acid-resistance to the enamel surface, in a dose-dependent manner at least up to 1500 ppm fluoride. Clinical significance Enamel erosive tissue loss is an increasing concern, associated with modern diets. This study demonstrated that sodium fluoride, in a conventional non-specialised dentifrice formulation, can promote repair of the earliest stages of enamel erosion after a single application, in a dose-dependent fashion across the fluoride concentration range used in mass-market dentifrices. This study is registered in the GlaxoSmithKline Study Register (ID RH01299), available at: www.gsk-clinicalstudyregister.com/study/RH01299 .

Objectives The present in vitro pH cycling study investigated potential differences between caries lesions created in fluorosed and sound enamel with regards to their responsiveness to fluoride under remineralizing conditions. Methods 360 human first molars (sound and fluorosed) were divided into four groups based on their Thylstrup–Fejerskov score (TF0-3). Each group was further divided into two treatment groups (n = 45): deionized water or 383 ppm fluoride. Artificial enamel caries lesions were created and pH cycled for 20 d using an established net remineralization model. Quantitative light-induced fluorescence was used throughout the study to investigate lesion severity and changes thereof. Data were analyzed using two-way ANOVA. Results There were no differences in lesion severity between all groups after lesion creation (plesion = 0.1934). The TF score vs. treatment interaction was significant at all other time points (p10 d = 0.0280; p20 d ≤ 0.0001; psecdemin = 0.0411). Relative differences in responsiveness to fluoride vs. deionized water increased with increasing TF scores. In comparison to lesions created in sound enamel, lesions created in enamel with moderate fluorosis (TF 2/3) were more prone to remineralization in the presence than in the absence of fluoride. Furthermore, lesions created in enamel with moderate fluorosis exhibited more remineralization in the presence of fluoride than lesions created in sound teeth, whereas the opposite was true for deionized water. Conclusion Bearing in mind the limitations of laboratory research, the extent of enamel fluorosis severity may directly impact subsequent lesion re- and progression as well as the lesion's responsiveness to fluoride. Clinical relevance Caries lesions in fluorotic teeth are more vulnerable to progression but respond more strongly to fluoride than those in non-impacted teeth.

This study explored differences in dental biofilm solids and fluid fluoride after ingestion of NaF or Na2FPO3 in milk or non-fluoridated milk. Eighteen volunteers ingested 1 mg fluoride in 200 mL of milk or 200 mL of non-fluoridated milk. Biofilm samples were collected at baseline, 30, 60, and 240 min and biofilm solids and fluid were micro-analyzed for fluoride. Analysis of variance was performed and the total delivery, retention, and clearance of fluoride to biofilm solids and fluid were estimated as the area under the curve between 0 and 240 min. No statistically significant differences were found for baseline values. Biofilm fluid fluoride values ranged from 0.11 ± 0.05 to 0.21 ± 0.08 µg F/mL while biofilm solid values ranged from 0.62 ± 0.39 to 1.75 ± 1.16 µg F/g. Biofilm fluid values were significantly lower at 60 min for Na2FPO3 in milk. Clearance profiles for biofilm fluid diverged after the initial 60 min. Na2FPO3 had a smaller area under the curve from 60 to 240 min than NaF. Results of this study indicate that the release and clearance of fluoride in biofilm vary among fluoridation compounds and that the concentrations in biofilm solids and fluid also vary and are not correlated to each other in many cases.

Objective Most of the commercially available fluoride varnishes (FV) have not been evaluated for their cariostatic properties. Consequently, the aim of this in vivo study was to investigate intra-oral fluoride retention and clearance patterns from three different FV. Methods Eighteen subjects (7–11 years) participated in a laboratory analyst-blinded, randomized, crossover study comparing the ability of 5% sodium fluoride varnishes (CavityShield-CS, Enamel Pro-EP, Vanish-V) to enhance fluoride concentrations in biofilm fluid, centrifuged and whole saliva over a period of 48 h after a single FV application. Results Similar fluoride concentration × time patterns were noted for all investigated FV and studied variables, with the highest fluoride concentrations observed for the first biological sample collected after FV application (30 min). Mean ± SE (area under fluoride clearance curve) values were (μg F/g or ml × min): biofilm fluid − CS (472 ± 191), EP (423 ± 75), V (1264 ± 279); centrifuged saliva − CS (42 ± 7), EP (19 ± 3), V (41 ± 8); whole saliva − CS (68 ± 11), EP (64 ± 10), V (60 ± 7). V delivered more fluoride to biofilm fluid than CS (p = 0.0116) and EP (p = 0.0065), which did not differ (p = 0.27). For centrifuged saliva, CS and V were not significantly different (p = 0.86), but resulted in higher fluoride retention than EP (p Conclusion The present study has shown that FV vary in their ability to deliver fluoride intra-orally potentially related to formulation differences. To what extent the present findings relate to clinical efficacy remains, however, to be determined. Clinical significance Clinical research that investigates fluoride release patterns into saliva and biofilm fluid from different FV products is insufficient. More research is needed to investigate different FV formulations for their efficacy in order to help clinicians make better evidence based treatment choices.

Fluoride is an element that affects teeth and bone formation in animals and humans. Though the use of systemic fluoride is an evidence-based caries preventive measure, excessive ingestion can impair tooth development, mainly the mineralization of tooth enamel, leading to a condition known as enamel fluorosis. In this study, we investigated the geochemical characterization of fluoride in water, table salt, active sediment, rock and soil samples in four endemic enamel fluorosis sentinel municipalities of the department of Huila, Colombia (Pitalito, Altamira, El Agrado and Rivera), and its possible relationship with the prevalence of enamel fluorosis in children. The concentration of fluoride in drinking water, table salt, active sediment, rock, and soil was evaluated by means of an ion selective electrode and the geochemical analyses were performed using X-ray fluorescence. Geochemical analysis revealed fluoride concentrations under 15 mg/kg in active sediment, rock and soil samples, not indicative of a significant delivery to the watersheds studied. The concentration of fluoride in table salt was found to be under the inferior limit (less than 180 μg/g) established by the Colombian regulations. Likewise, exposure doses for fluoride water intake did not exceed the recommended total dose for all ages from 6 months. Although the evidence does not point out at rocks, soils, fluoride-bearing minerals, fluoridated salt and water, the hypothesis of these elements as responsible of the current prevalence of enamel fluorosis cannot be discarded since, aqueducts might have undergone significant changes overtime.

Objectives The aim of the present in vitro study was to investigate the effects of fluoride concentration and temperature of milk on caries lesion rehardening under pH cycling conditions. Methods Incipient caries-like lesions were formed in human enamel specimens, characterized using Vickers surface microhardness (VHN) and assigned to seven treatment groups ( n = 18 per group): fluoride was tested at five levels (0, 2.5, 5, 10, 20 mg/l, all 22 °C) and milk temperature at three levels (4, 22, 60 °C), but only for 10 mg/l F. Lesions were pH cycled for 15d (4×/daily 10 min milk treatments, 1×/daily 4 h acid challenge, remineralization in human/artificial saliva mixture). VHN of specimens were measured again and changes from lesion baseline were calculated. Subsequently, enamel fluoride uptake (EFU) was determined using the micro drill technique. Results Lesions responded to fluoride in a dose–response manner with higher fluoride concentrations resulting in more lesion rehardening (20 > 10 ≥ 5 ≥ 2.5 > 0 mg/l F). Furthermore, fluoridated milk at 60 °C was found to be more efficacious than at 4 °C (60 ≥ 22 > 4 °C). EFU results were similar (20 > 10 > 5 > 2.5 ≥ 0 mg/l F; 60 > 22 ≥ 4 °C). Conclusions Both fluoride concentration and milk temperature are likely to contribute to the anti-caries potential of fluoridated milk.

Background/Aims: Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research. Methods: A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode. Results: Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies. Conclusion: The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values.

Objective: To determine differences in self-reported fluoride exposure and fluoride exposure biomarkers between two racial groups. Methods: Questionnaires regarding fluoride exposure, urine and water collection kits were distributed to African American and White 7-14-year-old children. Children received a dental exam for fluorosis. Water, urine, and saliva were analyzed for fluoride content. Questionnaire responses and results of sample analyses were compared and observed differences were analyzed. Results: 83 African American and 109 White children completed the study. Dental fluorosis was observed in 62.5 percent White and 80.1 percent African American children. Significant differences were found for fluorosis prevalence and severity between the groups (P

The mechanism of how fluoride causes fluorosis remains unknown. Exposure to fluoride can inhibit protein synthesis, and this may also occur by agents that cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold properly or become misfolded, ER stress response genes are induced that together comprise the unfolded protein response. Because ameloblasts are responsible for dental enamel formation, we used an ameloblast-derived cell line (LS8) to characterize specific responses to fluoride treatment. LS8 cells were growth-inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage-inducible proteins (GADD153/CHOP, GADD45alpha), binding protein (BiP/glucose-responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA-VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when GADD153 expression was inhibited by short interfering RNA treatment but remained unaffected by transient GADD153 overexpression. Analysis of control and GADD153(-/-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA fragmentation observed in the GADD153 null cells. We also demonstrate that mouse incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis. Low dose fluoride, such as that present in fluoridated drinking water, did not induce ER stress.

Objectives This randomized, cross-over in situ study investigated the impact of sodium fluoride dose and concentration in milk on caries lesion rehardening, fluoridation and acid resistance. Methods Twenty-eight subjects wore two gauze-covered enamel specimens with preformed lesions placed buccally on their mandibular partial dentures for three weeks. Participants used fluoride-free dentifrice throughout the study and consumed once daily one of the five study treatments: no fluoride in 200 ml milk (0F-200), 1.5 or 3 mg fluoride in either 100 (1.5F-100; 3F-100) or 200 ml milk (1.5F-200; 3F-200). After three weeks, specimens were retrieved. Knoop hardness was used to determine rehardening and resistance to a secondary acid challenge. Enamel fluoride uptake (EFU) was determined using a microbiopsy technique. Results A linear fluoride dose–response was observed for all study variables which exhibited similar overall patterns. All the treatments resulted in rehardening, with 0F-200 inducing the least and 3F-100 the most. Apart from 1.5F-200, all the treatments resulted in statistically significantly more rehardening compared to 0F-200. The fluoride doses delivered in 100 ml provided directionally although not statistically significantly more rehardening than those delivered in 200 ml milk. EFU data exhibited better differentiation between treatments: all fluoridated milk treatments delivered more fluoride to lesions than 0F-200; fluoride in 100 ml demonstrated statistically significantly higher EFU than fluoride in 200 ml milk. Findings for acid resistance were also more discerning than rehardening data. Conclusions The present study has provided further evidence for the anti-caries benefits of fluoridated milk. Both fluoride dose and concentration appear to impact the cariostatic properties of fluoride in milk.

While the clinical anticaries efficacy of fluoride toothpaste is now without question, our understanding of the relation of fluoride efficacy to brushing time and dentifrice quantity is limited. The aim of this in situ study was to determine how differences in brushing time and dentifrice quantity influence (i) fluoride distribution immediately after brushing, (ii) clearance of fluoride in saliva, (iii) enamel fluoride uptake (EFU) and (iv) enamel strengthening, via the increase in surface microhardness. The study compared brushing times of 30, 45, 60, 120 and 180 s with 1.5 g of dentifrice containing 1,100 µg/g fluoride as sodium fluoride. In addition, 60 s of brushing with 0.5 g dentifrice was evaluated. A longer brushing time progressively reduced retention of dentifrice in the brush, thereby increasing the amount delivered into the mouth. A longer brushing time also increased fluoride concentrations in saliva for at least 2 h after the conclusion of brushing, showing that increased contact time promoted fluoride retention in the oral cavity. There was a statistically significant positive linear relationship between brushing time and both enamel strengthening and EFU. Compared to 0.5 g dentifrice, brushing with 1.5 g dentifrice more than doubled the fluoride recovered in saliva after brushing and increased EFU. In conclusion, the results of this preliminary, short-term usage study suggest for the first time that both brushing time and dentifrice quantity may be important determinants both of fluoride retention in the oral cavity and consequent enamel remineralization.

Concurrent with the decline in dental caries has been an increase in the prevalence of dental fluorosis, a side-effect of exposure to greater than optimal levels of fluoride during amelogenesis. The mechanisms that underlie the pathogenesis of dental fluorosis are not known. We hypothesize that genetic determinants influence an individual’s susceptibility or resistance to develop dental fluorosis. We tested this hypothesis using a mouse model system (continuous eruption of the incisors) where genotype, age, gender, food, housing, and drinking water fluoride level can be rigorously controlled. Examination of 12 inbred strains of mice showed differences in dental fluorosis susceptibility/resistance. The A/J mouse strain is highly susceptible, with a rapid onset and severe development of dental fluorosis compared with that in the other strains tested, whereas the 129P3/J mouse strain is least affected, with minimal dental fluorosis. These observations support the contribution of a genetic component in the pathogenesis of dental fluorosis.

Objectives The influence of toothbrushing duration and dentifrice quantity on fluoride efficacy against dental caries is poorly understood. This study investigated effects of these two oral hygiene factors on enamel remineralisation (measured as surface microhardness recovery [SMHR]), enamel fluoride uptake (EFU), and net acid resistance (NAR) post-remineralisation in a randomized clinical study using an in situ caries model. Methods Subjects (n = 63) wore their partial dentures holding partially demineralised human enamel specimens and brushed twice-daily for two weeks, following each of five regimens: brushing for 120 or 45 s with 1.5 g of 1150 ppm F (as NaF) dentifrice; for 120 or 45 s with 0.5 g of this dentifrice; and for 120 s with 1.5 g of 250 ppm F (NaF) dentifrice. Results Comparing brushing for 120 s against brushing for 45 s, SMHR and EFU increased by 20.0% and 26.9% respectively when 1.5 g dentifrice was used; and by 22.8% and 19.9% respectively when 0.5 g dentifrice was used. Comparing brushing with 1.5 g against brushing with 0.5 g dentifrice, SMHR and EFU increased by 35.3% and 51.3% respectively when brushing for 120 s, and by 38.4% and 43.0% respectively when brushing for 45 s. Increasing brushing duration and dentifrice quantity also increased the NAR value. The effects of these two oral hygiene factors on SMHR, EFU, and NAR were statistically significant (p Conclusion Brushing duration and dentifrice quantity have the potential to influence the anti-caries effectiveness of fluoride dentifrices. Study NCT01563172 on ClinicalTrials.gov . Clinical significance The effect of two key oral hygiene regimen factors – toothbrushing duration and dentifrice quantity – on fluoride’s anticaries effectiveness is unclear. This 2-week home-use in situ remineralisation clinical study showed both these factors can influence fluoride bioactivity, and so can potentially affect fluoride’s ability to protect against caries.