Toxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses

Publikation: Beitrag in FachzeitschriftÜbersichtsartikel (Review)BeigetragenBegutachtung

Beitragende

  • Sabine Guth - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Stephanie Hueser - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Angelika Roth - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Gisela Degen - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Patrick Diel - , Deutsche Sporthochschule Köln (Autor:in)
  • Karolina Edlund - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Gerhard Eisenbrand - (Autor:in)
  • Karl-Heinz Engel - , Technische Universität München (Autor:in)
  • Bernd Epe - , Johannes Gutenberg-Universität Mainz (Autor:in)
  • Tilman Grune - , Deutsches Institut fur Ernahrungsforschung Potsdam-Rehbrucke (DIfE) (Autor:in)
  • Volker Heinz - , German Inst Food Technol DIL (Autor:in)
  • Thomas Henle - , Professur für Lebensmittelchemie (LC1), Technische Universität Dresden (Autor:in)
  • Hans-Ulrich Humpf - , Westfälische Wilhelms-Universität Münster (Autor:in)
  • Henry Jaeger - , Universität für Bodenkultur Wien (Autor:in)
  • Hans-Georg Joost - , Deutsches Institut fur Ernahrungsforschung Potsdam-Rehbrucke (DIfE) (Autor:in)
  • Sabine E. Kulling - , Max Rubner Institut (Autor:in)
  • Alfonso Lampen - , Bundesinstitut für Risikobewertung (BfR) (Autor:in)
  • Angela Mally - , Julius-Maximilians-Universität Würzburg (Autor:in)
  • Rosemarie Marchan - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Doris Marko - , Universität Wien (Autor:in)
  • Eva Muehle - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Michael A. Nitsche - , Ruhr-Universität Bochum (Autor:in)
  • Elke Roehrdanz - , Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) (Autor:in)
  • Richard Stadler - , Nestle (Autor:in)
  • Christoph van Thriel - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Stefan Vieths - , Paul-Ehrlich-Institut (Autor:in)
  • Rudi F. Vogel - , Technische Universität München (Autor:in)
  • Edmund Wascher - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Carsten Watzl - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)
  • Ute Noethlings - , Universität Bonn (Autor:in)
  • Jan G. Hengstler - , Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo) (Autor:in)

Abstract

Recently, epidemiological studies have suggested that fluoride is a human developmental neurotoxicant that reduces measures of intelligence in children, placing it into the same category as toxic metals (lead, methylmercury, arsenic) and polychlorinated biphenyls. If true, this assessment would be highly relevant considering the widespread fluoridation of drinking water and the worldwide use of fluoride in oral hygiene products such as toothpaste. To gain a deeper understanding of these assertions, we reviewed the levels of human exposure, as well as results from animal experiments, particularly focusing on developmental toxicity, and the molecular mechanisms by which fluoride can cause adverse effects. Moreover, in vitro studies investigating fluoride in neuronal cells and precursor/stem cells were analyzed, and 23 epidemiological studies published since 2012 were considered. The results show that the margin of exposure (MoE) between no observed adverse effect levels (NOAELs) in animal studies and the current adequate intake (AI) of fluoride (50 mu g/kg b.w./day) in humans ranges between 50 and 210, depending on the specific animal experiment used as reference. Even for unusually high fluoride exposure levels, an MoE of at least ten was obtained. Furthermore, concentrations of fluoride in human plasma are much lower than fluoride concentrations, causing effects in cell cultures. In contrast, 21 of 23 recent epidemiological studies report an association between high fluoride exposure and reduced intelligence. The discrepancy between experimental and epidemiological evidence may be reconciled with deficiencies inherent in most of these epidemiological studies on a putative association between fluoride and intelligence, especially with respect to adequate consideration of potential confounding factors, e.g., socioeconomic status, residence, breast feeding, low birth weight, maternal intelligence, and exposure to other neurotoxic chemicals. In conclusion, based on the totality of currently available scientific evidence, the present review does not support the presumption that fluoride should be assessed as a human developmental neurotoxicant at the current exposure levels in Europe.

Details

OriginalspracheEnglisch
Seiten (von - bis)1375-1415
Seitenumfang41
FachzeitschriftArchives of toxicology
Jahrgang94
Ausgabenummer5
PublikationsstatusVeröffentlicht - Mai 2020
Peer-Review-StatusJa

Externe IDs

Scopus 85084296144

Schlagworte

Schlagwörter

  • Sodium fluoride, Developmental neurotoxicity, Epidemiological studies, Animal studies, In vitro data, Risk assessment, ENDOPLASMIC-RETICULUM STRESS, SODIUM-FLUORIDE, OXIDATIVE STRESS, INTELLIGENCE QUOTIENT, DRINKING-WATER, PC12 CELLS, CHILDRENS INTELLIGENCE, AFFECT SPERMATOGENESIS, TESTICULAR TOXICITY, INTRACELLULAR CA2+