Biomarkers for the Assessment of Exposure to Fluoride in Adults.

To monitor deficient or excessive intakes of biologically available fluoride (F), various biological samples have been tested for use as biomarkers of human exposure to F. Most such studies have concerned children and often have only involved measurement of F in 1 or 2 types of sample. The present study investigated the relationships of F concentrations in biomarkers of F exposure; including plasma, saliva, hair, finger- and toenails, and daily urinary F excretion (UFE) with the total daily F intake (TDFI) of adults. TDFI was assessed in 60 healthy adults, aged ≥20 years; 31 lived in a low-F water area (LFA, 0.04 mg F/L) and 29 in a high-F water area (HFA, 3.05 mg F/L) of Nigeria. All volunteers provided at least 1 biomarker sample from the above list and completed a questionnaire to evaluate F intake from the diet and toothpaste ingestion. TDFI, UFE and F concentrations of biomarkers were statistically significantly higher in the HFA than in the LFA. There were strong statistically significant positive correlations between TDFI and UFE (ρ = 0.730, p < 0.001); plasma F (ρ = 0.729, p < 0.001); fasting whole saliva F (ρ = 0.653, p < 0.001) and hair F (ρ = 0.603, p < 0.001). The statistically significant positive correlations between TDFI and fingernail F (ρ = 0.502, p < 0.001) and between TDFI and toenail F (ρ = 0.556, p < 0.001) were moderate. In conclusion, this study has indicated the usefulness of 24-h UFE as well as F concentration in plasma, fasting whole saliva and hair as biomarkers of contemporary or sub-chronic F exposure in groups of adults. However, they do not appear to have the necessary sensitivity to predict F exposure in individuals.

Fluoride retention in infants living in fluoridated and non-fluoridated areas: effects of weaning.

Limited knowledge is available on total fluoride exposure, excretion and retention in infants, despite the first year of human life being the critical period for dental development and risk of dental fluorosis. This study investigated total daily fluoride intake (TDFI), excretion (TDFE) and retention (TDFR) in infants living in fluoridated and non-fluoridated water areas at pre- and post-weaning stages of development. Healthy infants, aged 0-12 months, were recruited and their TDFI (mg/kg body weight (BW) per d), from diet and toothpaste ingestion, was assessed over a 3-d period using a dietary diary and tooth-brushing questionnaire. TDFE (mg/kg BW per d) was estimated by collecting 48-h urine and faeces. TDFR (mg/kg BW per d) was estimated by subtracting TDFE from TDFI. A total of forty-seven infants completed the study: sixteen at pre-weaning and thirty-one at post-weaning stages, with a mean age of 3·4 and 10·0 months, respectively. TDFI was lower in the non-fluoridated area (P<0·001) and at the pre-weaning stage (P=0·002) but higher in formula-fed infants (P<0·001). TDFE was mainly affected by type of feeding, with higher excretion in formula-fed infants (P<0·001). TDFR was lower in the non-fluoridated area (P<0·001) and at the pre-weaning stage (P<0·001) but higher in formula-fed infants (P=0·001). In conclusion, a relatively large proportion of fluoride intake is retained in the body in weaned infants. This is an important consideration in fluoride-based prevention programmes, with goals to maximise caries prevention while minimising the risk of dental fluorosis.

Comparison of total ionic strength adjustment buffers III and IV in the measurement of fluoride concentration of teas.

BACKGROUND: Tea is the second most consumed drink in the UK and a primary source of hydration; it is an important source of dietary fluoride (F) for consumers and also abundant in aluminium (Al). Varying ranges of F concentrations in teas have been reported worldwide which may be, in part, due to differences in analytical techniques used to measure this ion. AIM: The effect of using total ionic adjustment buffers (TISAB) III or IV when measuring F concentration of black teas available in the UK was investigated and compared. Based on this evaluation, the effects of three different infusion times, 1 min, 10 min and 1 h, caffeine content and tea form on the F contents of the tea samples were investigated. METHODS: The F concentrations of 47 tea samples were measured directly using a fluoride ion-selective electrode (F-ISE), TISAB III and IV and infusion times of 1 min, 10 min and 1 h. RESULTS: Mean (SD) F concentration of tea samples for all infusion times was statistically significantly higher ( p < 0.001) measured by TISAB IV (4.37 (2.16) mg/l) compared with TISAB III (3.54 (1.65) mg/l). A statistically significant positive correlation ( p < 0.001) was found between Al concentration (mg/l) and differences in F concentration (mg/l) measured using the two TISABs; the difference in F concentration measured by the two TISABs increased with the magnitude of Al concentration. CONCLUSION: Due to higher concentrations of F and Al in teas and their complexing potential, use of TISAB IV facilitates more accurate measurement of F concentration when using an F-ISE and a direct method.

Fluoride concentrations in a range of ready-to-drink beverages consumed in Heilongjiang Province, north-east China.

Consumption of ready-to-drink beverages, as a potential source of fluoride (F), has increased considerably in China over the last decade. To help inform the public and policy makers, this study aimed to measure F concentration of ready-to-drink beverages on sale in Heilongjiang province, north east China. Three batches of 106 drink products manufactured by 26 companies were purchased from the main national supermarkets in Harbin, Heilongjiang province, China. The F concentration of all samples was determined, in triplicate, using a fluoride ion-selective electrode in conjunction with a meter and a direct method of analysis. The products were categorised into 10 groups according to product type. F concentrations of the samples ranged from 0.012-1.625 mg/l with a mean of 0.189 mg/l and a median of 0.076 mg/l. More than half of the products (55%) had an F concentration of ≤0.1 mg/l, while <5% had a F concentration of >0.7 mg/l. The 'tea with milk' group contained the highest mean F concentration (1.350 mg/l), whereas the lowest mean F concentration (0.027 mg/l) was found for the 'fruit juice' group. For some products, such as tea, fruit juice and carbonated beverages, there were substantial variations in F concentration between batches, manufacturers and production sites. In conclusion, ready-to-drink products (apart from tea), sold in Heilongjiang province, China, when consumed in moderation are unlikely to constitute a substantial risk factor for the development of dental or skeletal fluorosis.

Fluoridated toothpaste: usage and ingestion of fluoride by 4- to 6-yr-old children in England.

Fluoridated toothpaste is effective for dental caries control, yet may be a risk factor for dental fluorosis. This study aimed to quantify fluoride ingestion from toothpaste by children and to investigate the effects of age, gender, and social class on the amount of fluoride ingested per toothbrushing session. Sixty-one children, 4-6 yr of age, were recruited: 38 were from low socio-economic (LSE) areas of Newcastle, UK, and 23 were from high socio-economic (HSE) areas of Newcastle, UK. All expectorated saliva, rinse water (if used), and residual toothpaste were collected after brushing at home and were analysed for fluoride. Of the children, 74% and 69% from HSE and LSE areas, respectively, claimed that they brushed twice per day. The mean (SD) weight of toothpaste dispensed was 0.67 (0.36) g. The mean (SD) amount of fluoride ingested per toothbrushing session and per day was 17.0 (14.7) and 29.3 (32.8) µg kg(-1) of body weight, respectively. Daily fluoride intake per kilogram of body weight did not differ significantly between children from LSE and HSE areas. Fluoride intake per toothbrushing session was significantly influenced by weight of toothpaste, its fluoride concentration, and the child's age. Whilst the average amount of toothpaste used per toothbrushing session was more than twice the recommended amount (of 0.25 g), only one child had a daily fluoride intake that exceeded the tolerable upper intake level of 0.1 mg kg(-1) of body weight for this age group.

Web search engines reveal conflicting information about water fluoridation.

Aim To evaluate web search engines' informational content regarding community water fluoridation (CWF) when accessed from the UK.Methods The search engine result pages (SERPs) regarding CWF from Google were identified, the content was analysed for themes and sentiments, and Google Trends information on CWF was examined.Results The SERPs were predominantly in favour of CWF. Anti-fluoridation themes were observed in SERPs that presented the arguments supporting and opposing CWF with equanimity, irrespective of the quality of scientific evidence. Hence, a web search for CWF yields conflicting information. Correlation is observed between current affairs and public interest in CWF.Conclusion UK residents seeking online CWF advice may experience confusion due to the prevalent conflicting information, which may influence their decision-making. Dental health professionals, public health practitioners and policymakers should strive to improve the information provision on CWF online.

Effect of Physical Exercise and Genetic Background on Glucose Homeostasis and Liver/Muscle Proteomes in Mice.

We compared the parameters related to glucose homeostasis, and liver and muscle proteomes in fluorosis-susceptible (A/J; S) and fluorosis-resistant (129P3/J; R) mice in response to fluoride (F) exposure and exercise. Ninety male mice (45 R-mice and 45 S-mice) were randomized into three groups: (SI; RI) No-F, No-Exercise, (SII; RII) 50 ppm F, No-Exercise, (SIII; RIII) 50 ppm F, Exercise. Overall, mean F concentrations in the plasma and femur were significantly higher in R-mice compared with S-mice. In R-mice, exercise resulted in an increase in F accumulation in the femur. In S-mice, the mean plasma glucose level was significantly higher in Group II compared with Groups I and III. There was an increase in liver proteins involved in energy flux and antioxidant enzymes in non-exercise groups (I, II) of S-mice in comparison with the corresponding groups of R-mice. The results also showed a decrease in muscle protein expression in Group I S-mice compared with their R-mice counterparts. In conclusion, the findings suggest an increased state of oxidative stress in fluorosis-susceptible mice that might be exacerbated by the treatment with F. In addition, fluorosis-susceptible mice have plasma glucose levels higher than fluorosis-resistant mice on exposure to F, and this is not affected by exercise.

The use of urinary fluoride excretion to facilitate monitoring fluoride intake: A systematic scoping review.

BACKGROUND: As a recognised effective and economical agent for dental caries prevention, fluoride has been used in many different fluoridation schemes implemented across the world. Considering the narrow 'dose-gap' between the benefit of caries reduction and the risk of dental fluorosis, it is recommended that fluoride intake is monitored by measuring urinary fluoride excretion. The aim of this scoping review is to map the current literature/evidence on fluoride intake and excretion studies in relation to the study population, settings, type of study design, methodology, and analytical approach. METHODS: Embase/Ovid, MEDLINE/Ovid, CINAHL/EBSCO, Scopus/Elsevier were searched for relevant articles until April 2018. Studies were included if they reported intake and excretion of fluoride in healthy humans of all age groups. Findings were explored using a narrative synthesis to summarise studies characteristics and outcome measures. RESULTS: Removal of duplicates from the originally 2295 identified records yielded 1093 studies of which 206 articles were included. Only 21.6% of the studies were conducted in children (<8-year-olds). Most studies (38.8%) used drinking water concentration as a proxy for fluoride intake, whereas only 11.7% measured fluoride intake from all sources. Of the 72 studies that measured dietary fluoride intake, only 10 reported the validity of the employed dietary assessment method. Only 14 studies validated the urine sample collection methods. No information on the validity of the employed analytical method was reported by the majority (64.6%) of studies. Only a small proportion (8.7%) of the included studies investigated the association between fluoride intake and excretion. CONCLUSION: The findings reveal much variability in terms of conducting the studies and reporting the findings, illustrating a high heterogeneity in data collection across settings and populations. Future studies should provide more detail on sampling technique, measurement protocols (including validation), and on clearly defining the relationship between intake and urinary excretion of fluoride.

Prevalence and extent of enamel defects in the permanent teeth of 8-year-old Nigerian children.

OBJECTIVES: Enamel formation is a vulnerable developmental process, susceptible to environmental influences such as excessive systemic fluoride (F) exposure and infant/childhood disease. This study determined prevalence and extent of developmental enamel defects (DDE) and dental fluorosis in 8-year-old Nigerians and explored associations with key predictors. METHODS: A sample of 322 healthy 8-year-olds (155 males, 167 females) from primary schools in lower and higher water F areas of (i) rural and (ii) urban parts of Oyo State in south-west Nigeria (n = 4 areas) (in which the mean (SD) F concentration of community water supplies ranged from 0.07 (0.02) to 2.13 (0.64) mg F/L) were dentally examined using modified DDE (mDDE) and Thylstrup and Fejerskov (TF) indices. Drinking waters, cooking waters and toothpaste samples were analysed for F concentration using a F ion-selective electrode (F-ISE). Information on infant/childhood diseases, infant feeding and tooth cleaning practices was obtained from parents/legal guardians. Data were analysed using ANOVA, chi-square tests, Spearman correlation and binary logistic regression as appropriate. RESULTS: Mean (SD) F concentration of actual drinking and actual cooking waters consumed by participants was 0.25 (0.20) and 0.24 (0.14) mg F/L respectively in the urban higher F area; 1.11 (1.00) and 1.16 (1.02) mg F/L, respectively in the rural higher F area (P < .05). Overall, mouth prevalence of DDE in the permanent dentition was 61.2% with a mean (SD) of 2.4 (2.2) index teeth affected. Dental fluorosis mouth prevalence was 29.8% with a mean of 2.1 (3.7) teeth affected. Prevalence and extent of DDE and dental fluorosis were greater in higher F than lower water F areas (P < .001). A weak positive correlation was seen between extent of dental fluorosis and drinking water F concentration (ρ = 0.28). The absence of infant/childhood disease was associated with a lower risk of DDE being present (P = .001), with an odds ratio of 0.43 (95% CI = 0.26, 0.71). Gender was a statistically significant (P = .014) predictor for dental fluorosis with females having a higher risk OR 1.94 (95% CI = 1.14, 3.28) of dental fluorosis than males. CONCLUSIONS: In these Nigerian 8-year-olds (n = 322), mouth prevalence of DDE was 61.2% (mean (SD) teeth affected = 2.4 (2.2)), and a key positive predictor was a history of infant/childhood disease. With 29.8% of these children exhibiting dental fluorosis (mean (SD) teeth affected = 2.1(3.7)), drinking water F concentration was identified as a positive predictor, along with gender, with females more at risk of dental fluorosis than males.

Effect of chronic exercise on fluoride metabolism in fluorosis-susceptible mice exposed to high fluoride.

The present study investigated the effect of chronic exercise on fluoride (F) metabolism in fluorosis-susceptible mice exposed to high-F and explored the relationship between F concentrations in bone and plasma. Thirty male mice were randomised into three groups: Group I (No-F, No-Exercise), Group II (50 ppmF, No-Exercise), Group III (50 ppmF, Exercise). Body weight and physical performance of all mice were measured at baseline and end of experiment. F concentrations of plasma and bone were measured at the end of experiment. Mean plasma F concentration was significantly higher (p < 0.001) in Groups II and III compared with Group I. Mean bone F concentration was also significantly higher (p < 0.01) in Groups II and III compared with Group I. There was a significant correlation (p = 0.01, r = 0.54) between F concentration of plasma and bone. Mean body weight of Group I mice was significantly higher than Group II (p < 0.001) and Group III (p = 0.001) mice at the end of the experiment. This study, which provides the first data on the effect of chronic exercise on F metabolism in fluorosis-susceptible mice, suggests no effect of chronic exercise on F in plasma and bone. However, exposure to high-F resulted in lower body weight and exercise capacity in mice.

Total daily fluoride intake and fractional urinary fluoride excretion in 4- to 6-year-old children living in a fluoridated area: weekly variation?

OBJECTIVES: Risk of development of dental fluorosis may increase with even a short-term increase in fluoride (F) intake during tooth formation. Considering the wide variations in F concentrations of different food and drinks, it is important to assess short-term differences in F intake and consequently fractional urinary F excretion (FUFE) in children, which provide an indication of F body burden. Therefore, the aim of this study was to investigate weekly variation in total daily F intake (TDFI) and its sources and fractional urinary F excretion (FUFE) in 4- to 6-year-olds living in a fluoridated area in the UK. METHODS: Sixty-one children were surveyed twice with a 1-week gap between surveys. Dietary F intake was assessed by 'food-diary' and 'duplicate-plate collection'. Toothbrushing expectorate (saliva/toothpaste) was collected to estimate F intake from toothpaste ingestion. TDFI was calculated from dietary F intake and toothpaste ingestion. Daily urinary F excretion (DUFE) was estimated by collecting 24-h urine samples and FUFE was calculated from DUFE and TDFI [FUFE = (DUFE/TDFI) × 100]. RESULTS: The overall mean TDFI, DUFE and FUFE for all children were 0.056 (SD 0.036) mg/kgbw/day, 0.018 (SD 0.007) mg/kgbw/day and 39 (SD 20)%, respectively. The mean (95% CI) difference between the 2 weeks studied was 0.004 (-0.004, 0.011) mg/kgbw/day for TDFI, 0.002 (-0.001, 0.004) mg/kgbw/day for DUFE and 1 (-6, 8)% for FUFE. CONCLUSIONS: Mean TDFI and FUFE did not vary statistically significantly with week and therefore one set of data collection from a group of children living in a temperate climate could be sufficient to monitor F exposure and F body burden in community prevention programmes for oral health.

Fluoride content of ready-to-feed (RTF) infant food and drinks in the UK.

BACKGROUND: The level of Fluoride exposure needed to cause dental fluorosis is not known precisely. An awareness of total F intake from all sources, especially during the critical stages of dental development during infancy and early childhood, is important in preventing the development of dental fluorosis. OBJECTIVES: The aim of the study was to measure F content of ready-to-feed (RTF) infant drinks and foods in the UK. METHODS: In total, 122 infant foods were analysed for F concentrations, in triplicate, indirectly by an acid diffusion method and 25 infant drinks analysed directly using an F-ion-selective electrode after addition of TISABIII. RESULTS: The median (range) F concentration was 0.110 (0.030-0.221) µg/g for breakfast cereals, 0.112 (0.040-1.200) µg/g for savoury meals, 0.056 (0.030-0.379) µg/g for desserts, 0.044 (0.020-0.191) µg/g for fruits, 0.196 (0.040-0.397) µg/g for baked goods, 0.069 (0.050-0.148) µg/ml for juices, 0.016 (0.009-0.030) µg/ml for milks and 0.041 (0.022-0.069) µg/ml for waters. The median (range) F concentration of all RTF infant foods and drinks by recommended age of consumption was 0.029 (0.010-0.245), 0.088 (0.020-0.500), 0.108 (0.100-0.510) and 0.108 (0.060-1.200) µg/g for infants from birth, 4+ month, 6+ month and 10+ month, respectively. CONCLUSION: The results suggest that the F concentrations of UK-marketed RTF infant foods, drinks and formula milk are not sufficiently high to be a risk factor for dental fluorosis, if consumption is within the limits recommended for infants and young children.

Impact of water fluoride concentration on the fluoride content of infant foods and drinks requiring preparation with liquids before feeding.

OBJECTIVES: To measure the fluoride (F) content of infant foods and drinks requiring reconstitution with liquids prior to consumption and to determine the impact of water F concentration on their F content, as consumed, by measuring F content before and after preparation. METHODS: In total, 58 infant powdered formula milks, dry foods and concentrated drinks were prepared with deionized water (<0.02 ppm F) nonfluoridated (0.13 ppm F) and fluoridated (0.90 ppmF) water. The F concentrations of drink samples were measured directly using a fluoride-ion-selective electrode after addition of TISAB III, and food samples and formula milks measured indirectly by an acid diffusion method. RESULTS: The overall range of F concentrations of all the nonreconstituted samples, in their prepreparation dry or concentrated forms, was from 0.06 to 2.99 µg/g with the highest F concentration for foods found in the dry 'savoury meals' (a combination of vegetables and chicken or cheese or rice) group. However, when the samples were reconstituted with nonfluoridated water, the mean F concentrations of prepared 'concentrated juices', 'pasta and rice', 'breakfast cereals', 'savoury meals' and 'powdered infant formula milks' were 0.38, 0.26, 0.18, 0.16 and 0.15 µg/g, respectively. The corresponding mean F concentrations were 0.97, 1.21, 0.86, 0.74 and 0.91 µg/g, respectively, when the same samples were prepared with fluoridated water. CONCLUSION: Although some nonreconstituted infant foods/drinks showed a high F concentration in their dry or concentrated forms, the concentration of F in prepared foods/drinks primarily reflected the F concentration of liquid used for their preparation. Some infant foods/drinks, when reconstituted with fluoridated water, may result in a F intake in infants above the suggested optimum range (0.05-0.07 mg F/kg body weight) and therefore may put infants at risk of developing dental fluorosis. Further research is necessary to determine the actual F intake of infants living in fluoridated and nonfluoridated communities using reconstituted infant foods and drinks.