Fluoride Action Network

Abstract

Due to practical difficulties in quantifying fluoride exposure, the ability of various biomarkers to predict exposure has been investigated previously. However, the results are inadequate for validation of their application and usefulness. This study aimed to investigate the association between contemporary/recent biomarkers of fluoride exposure and total daily fluoride intake (TDFI) of children with large differences in fluoride exposure through drinking water. TDFI was assessed in 61 healthy 4- to 5-year-old children who provided at least 1 biomarker sample; 32 lived in a low-fluoride area (0.04 mg F/L) and 29 lived in a high-fluoride area (3.05 mg F/L). Validated questionnaires were administered to evaluate fluoride intake from diets (including water) and toothpaste ingestion. Daily urinary fluoride excretion (UFE) and fluoride concentrations in plasma, fasting whole saliva, hair, and nails (toenails/fingernails) were evaluated and related to total fluoride exposure. TDFI, UFE, and fluoride concentrations of biomarkers were statistically significantly higher in the high-fluoride area than in the low-fluoride area. There was a strong statistically significant positive correlation between TDFI and UFE (? = 0.756, p < 0.001); plasma fluoride concentration (? = 0.770, p < 0.001); and toenail fluoride concentration (? = 0.604, p < 0.001). The statistically significant positive correlation between TDFI and fingernail fluoride concentration (? = 470, p < 0.001) as well as between TDFI and fasting whole saliva fluoride concentration (? = 0.453, p = 0.001) was moderate, whereas it was weak between TDFI and hair fluoride concentration (? = 0.306, p = 0.027). In conclusion, the current study confirmed the suitability of 24-h urine samples for estimating fluoride exposure in children. The strong correlations between TDFI and fluoride in plasma and toenails also suggest these biomarkers may be considered for health risk assessments of fluoride in children who are susceptible to development of dental fluorosis.

References

  1. Bashash M, Thomas D, Hu H, Martinez-Mier EA, Sanchez BN, Basu N, et al. Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6-12 Years of Age in Mexico. Environ Health Perspect. 2017 Sep;125(9):097017.
  2. Bashash M, Marchand M, Hu H, Till C, Martinez-Mier EA, Sanchez BN, et al. Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6-12years of age in Mexico City. Environ Int. 2018 Dec;121(Pt 1):658-666.
  3. Boros I, Keszler P, Bánóczy J. Fluoride concentrations of unstimulated whole and labial gland saliva in young adults after fluoride intake with milk. Caries Res. 2001 May-Jun;35(3):167–72. Pubmed/Medline (NLM)
  4. Burt BA. The changing patterns of systemic fluoride intake. J Dent Res. 1992 May;71(5):1228–37. Pubmed/Medline (NLM)
  5. Buzalaf MA, Massaro CS, Rodrigues MH, Fukushima R, Pessan JP, Whitford GM, et al. Validation of fingernail fluoride concentration as a predictor of risk for dental fluorosis. Caries Res. 2012;46(4):394–400. Pubmed/Medline (NLM)
  6. Buzalaf MA, Rodrigues MH, Pessan JP, Leite AL, Arana A, Villena RS, et al. Biomarkers of fluoride in children exposed to different sources of systemic fluoride. J Dent Res. 2011 Feb;90(2):215–9. Pubmed/Medline (NLM)
  7. Buzalaf MA, Whitford GM. Fluoride Metabolism. Monogr Oral Sci. 2011;22:20–36.
  8. Czarnowski W, Krechniak J. Fluoride in the urine, hair, and nails of phosphate fertiliser workers. Br J Ind Med. 1990 May;47(5):349–51. Pubmed/Medline (NLM)
  9. Duckworth RM, Morgan SN. Oral fluoride retention after use of fluoride dentifrices. Caries Res. 1991;25(2):123–9. Pubmed/Medline (NLM)
  10. Duckworth RM, Morgan SN, Murray AM. Fluoride in saliva and plaque following use of fluoride-containing mouthwashes. J Dent Res. 1987 Dec;66(12):1730–4. Pubmed/Medline (NLM)
  11. Ekstrand J, Fomon SJ, Ziegler EE, Nelson SE. Fluoride pharmacokinetics in infancy. Pediatr Res. 1994 Feb;35(2):157–63. Pubmed/Medline (NLM)
  12. Ericsson Y. Fluoride excretion in human saliva and milk. Caries Res. 1969;3(2):159–66. Pubmed/Medline (NLM)
  13. Evan J. Straightforward statistics for the behavioral sciences in: Percept Mot Skills. Pacific Grove (California): Brooks/Cole Publishing; 1996.
  14. Fukushima R, Rigolizzo DS, Maia LP, Sampaio FC, Lauris JR, Buzalaf MA. Environmental and individual factors associated with nail fluoride concentration. Caries Res. 2009;43(2):147–54. Pubmed/Medline (NLM)
  15. GBD 2016 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep;390:1345–1422.
  16. Harding MA, O’Mullane DM. Water fluoridation and oral health. Acta Med Acad. 2013 Nov;42(2):131–9.
  17. Hellwig E, Lennon AM. Systemic versus topical fluoride. Caries Res. 2004 May-Jun;38(3):258–62. Pubmed/Medline (NLM)
  18. Ibiyemi O, Zohoori FV, Valentine RA, Maguire A. Fluoride intake and urinary fluoride excretion in 4- and 8-year-old children living in urban and rural areas of Southwest Nigeria. Community Dent Oral Epidemiol. 2018 Oct;46(5):482–91. Pubmed/Medline (NLM)
  19. Idowu O. Biomarkers of fluoride exposure in children and adults [PhD]. Middlesbrough: Teesside University, School of Health and Social Care; 2018.
  20. Joshi NA, Ajithkrishnan CG. Scalp Hair as Biomarker for Chronic Fluoride Exposure among Fluoride Endemic and Low Fluoride Areas: A Comparative Study. Int J Trichology. 2018 Mar-Apr;10(2):71–5. Pubmed/Medline (NLM)
  21. Khan A, Moola MH, Cleaton-Jones P. Global trends in dental fluorosis from 1980 to 2000: a systematic review. SADJ. 2005 Nov;60(10):418–21. Pubmed/Medline (NLM)
  22. Kono K, Yoshida Y, Watanabe M, Orita Y, Dote T, Bessho Y. Urine, serum and hair monitoring of hydrofluoric acid workers. Int Arch Occup Environ Health. 1993;65(1 Suppl):S95–8. Pubmed/Medline (NLM)
  23. Kono K, Yoshida Y, Watanabe M, Watanabe H, Inoue S, Murao M, et al. Elemental analysis of hair among hydrofluoric acid exposed workers. Int Arch Occup Environ Health. 1990;62(1):85–8. Pubmed/Medline (NLM)
  24. Lar AU, Dibal H, Schoeneich K. Fluoride in Groundwater in Nigeria: Origin and Human Health Impact. Am J Environ Prot. 2014;3(6-2):66-69.
  25. Levy FM, Bastos JR, Buzalaf MA. Nails as biomarkers of fluoride in children of fluoridated communities. J Dent Child (Chic). 2004 May-Aug;71(2):121–5. Pubmed/Medline (NLM)
  26. Levy SM, Zarei-M Z. Evaluation of fluoride exposures in children. ASDC J Dent Child. 1991 Nov-Dec;58(6):467–73. Pubmed/Medline (NLM)
  27. Lima-Arsati YB, Martins CC, Rocha LA, Cury JA. Fingernail may not be a reliable biomarker of fluoride body burden from dentifrice. Braz Dent J. 2010;21(2):91–7.Pubmed/Medline (NLM)
  28. Linhares DP, Garcia PV, Amaral L, Ferreira T, Cury JA, Vieira W, et al. Sensitivity of two biomarkers for biomonitoring exposure to fluoride in children and women: A study in a volcanic area. Chemosphere. 2016 Jul;155:614–20. Pubmed/Medline (NLM)
  29. Mandinic Z, Curcic M, Antonijevic B, Carevic M, Mandic J, Djukic-Cosic D, et al. Fluoride in drinking water and dental fluorosis. Sci Total Environ. 2010 Aug;408(17):3507–12. Pubmed/Medline (NLM)
  30. Martínez-Mier EA, Cury JA, Heilman JR, Katz BP, Levy SM, Li Y, et al. Development of gold standard ion-selective electrode-based methods for fluoride analysis. Caries Res. 2011;45(1):3–12. Pubmed/Medline (NLM)
  31. Martínez-Mier EA, Soto-Rojas AE, Ureña-Cirett JL, Stookey GK, Dunipace AJ. Fluoride intake from foods, beverages and dentifrice by children in Mexico. Community Dent Oral Epidemiol. 2003 Jun;31(3):221–30. Pubmed/Medline (NLM)
  32. Martins CC, Paiva SM, Cury JA. Effect of discontinuation of fluoride intake from water and toothpaste on urinary excretion in young children. Int J Environ Res Public Health. 2011 Jun;8(6):2132–41
  33. Oliveby A, Lagerlöf F, Ekstrand J, Dawes C. Studies on fluoride excretion in human whole saliva and its relation to flow rate and plasma fluoride levels. Caries Res. 1989;23(4):243–6. Pubmed/Medline (NLM)
  34. Oliveby A, Twetman S, Ekstrand J. Diurnal fluoride concentration in whole saliva in children living in a high- and a low-fluoride area. Caries Res. 1990;24(1):44–7. Pubmed/Medline (NLM)
  35. O’Mullane DM, Baez RJ, Jones S, Lennon MA, Petersen PE, Rugg-Gunn AJ, et al. Fluoride and Oral Health. Community Dent Health. 2016 Jun;33(2):69–99. Pubmed/Medline (NLM)
  36. Ophaug R. Determination of fluorine in biological materials: reaction paper. Adv Dent Res. 1994 Jun;8(1):87–91. Pubmed/Medline (NLM)
  37. Pessan JP, Buzalaf MR. Historical and recent biological markers of exposure to fluoride. Monogr Oral Sci. 2011;22:52–65. Pubmed/Medline (NLM)
  38. Rugg-Gunn AJ, Villa AE, Buzalaf MR. Contemporary biological markers of exposure to fluoride. Monogr Oral Sci. 2011;22:37–51. Pubmed/Medline (NLM)
  39. Schamschula RG, Duppenthaler JL, Sugár E, Un PS, Tóth K, Barmes DE. Fluoride intake and utilization by Hungarian children: associations and interrelationships. Acta Physiol Hung. 1988;72(2):253–61. Pubmed/Medline (NLM)
  40. Schamschula RG, Sugár E, Un PS, Tóth K, Barmes DE, Adkins BL. Physiological indicators of fluoride exposure and utilization: an epidemiological study. Community Dent Oral Epidemiol. 1985 Apr;13(2):104–7. Pubmed/Medline (NLM)
  41. Thomas DB, Basu N, Martinez-Mier EA, Sánchez BN, Zhang Z, Liu Y, et al. Urinary and plasma fluoride levels in pregnant women from Mexico City. Environ Res. 2016 Oct;150:489–95. Pubmed/Medline (NLM)
  42. Villa A, Anabalon M, Zohouri V, Maguire A, Franco AM, Rugg-Gunn A. Relationships between fluoride intake, urinary fluoride excretion and fluoride retention in children and adults: an analysis of available data. Caries Res. 2010;44(1):60–8. Pubmed/Medline (NLM)
  43. Whitford GM. Monitoring fluoride exposure with fingernail clippings. Schweiz Monatsschr Zahnmed. 2005;115(8):685–9. Pubmed/Medline (NLM)
  44. Whitford GM, Thomas JE, Adair SM. Fluoride in whole saliva, parotid ductal saliva and plasma in children. Arch Oral Biol. 1999 Oct;44(10):785–8. Pubmed/Medline (NLM)
  45. WHO Expert Committee on Oral Health Status and Fluoride Use & World Health Organization. Fluorides and oral health. Report of a WHO Expert Committee on Oral Health Status and Fluoride Use [?meeting held in Geneva from 22 to 28 November 1993]?. Geneva, Switzerland: WHO; 1994. https://apps.who.int/iris/handle/10665/39746.
  46. World Health Organization. Basic methods for assessing renal fluoride excretion in community prevention programmes for oral health. Geneva, Switzerland: WHO; 2014. https://apps.who.int/iris/handle/10665/112662.
  47. Yao K, Gron P. Fluoride concentration in duct saliva and whole saliva. Caries Res. 1970;4(4):321–31. Pubmed/Medline (NLM)
  48. Zipkin I, Likins RC, McClure F, Steere AC. Urinary fluoride levels associated with use of fluoridated drinking waters. Public Health Rep. 1956 Aug;71(8):767–72. Crossref (DOI)
  49. Zohoori FV. Summary of General Discussion and Conclusions. Adv Dent Res. 2018 Mar;29(2):183–5. Pubmed/Medline (NLM)
  50. Zohoori FV, Duckworth RM, Omid N, O’Hare WT, Maguire A. Fluoridated toothpaste: usage and ingestion of fluoride by 4- to 6-yr-old children in England. Eur J Oral Sci. 2012 Oct;120(5):415–21. Pubmed/Medline (NLM)
  51. Zohoori FV, Maguire A. Determining an upper reference value for the urinary fluoride-creatinine ratio in healthy children younger than 7 years. Caries Res. 2017;51(4):283–9. Pubmed/Medline (NLM)
  52. Zohouri FV, Rugg-Gunn AJ. Sources of dietary fluoride intake in 4-year-old children residing in low, medium and high fluoride areas in Iran. Int J Food Sci Nutr. 2000 Sep;51(5):317–26. Pubmed/Medline (NLM)
  53. Zohouri FV, Swinbank CM, Maguire A, Moynihan PJ. Is the fluoride/creatinine ratio of a spot urine sample indicative of 24-h urinary fluoride? Community Dent Oral Epidemiol. 2006 Apr;34(2):130–8. Pubmed/Medline (NLM)