NTP (2024)

This is a paper for discussion. This does not represent the views of the Committee and should not be cited.

69.             Key endpoints covered: neurodevelopment and cognition.

70.             Databases: BIOSIS (Thomson Reuters); EMBASE; PsycINFO (APA PsycNet); PubMed (NLM); Scopus (Elsevier); WoS (Thomson Reuters, WoS indexes the journal Fluoride); Supplemental Chinese Database Literature Search (CNKI and Wanfang).

Key search 1 - PubMed

71.             Literature search date: 1 April 2019 (updated 1 May 2020 (human only)[10] and October 2023 (children’s IQ only)).

72.             Search concept: Fluorides AND neurodevelopment/cognition (see below for further details).

73.             Chemical search terms (fluorides concept): ((Fluorides[mh[11]:noexp] OR fluorides, topical[mh] OR sodium fluoride[mh] OR Fluorosis, Dental[mh] OR fluorosis[tiab] OR fluorid*[tiab] OR flurid*[tiab] OR fluorin*[tiab] OR florin*[tiab]) NOT (18F[tiab] OR f-18[tiab] OR 19F[tiab] OR f-19[tiab] OR f-labeled[tiab] OR "fluorine-18"[tiab] OR "fluorine-19"[tiab] OR pet-scan[tiab] OR radioligand*[tiab])).

74.             Neurodevelopment/cognition concept: ((Aryl Hydrocarbon Hydroxylases[mh] OR Aryl Hydrocarbon Receptor Nuclear Translocator[mh] OR Behavior and Behavior Mechanisms[mh] OR Gene Expression Regulation[mh] OR Glucuronosyltransferase[mh] OR Intelligence tests[mh] OR Malate Dehydrogenase[mh] OR Mediator Complex Subunit 1[mh] OR Mental disorders[mh] OR Mental processes[mh] OR Monocarboxylic Acid Transporters[mh] OR Myelin Basic Protein[mh] OR nervous system[mh] OR nervous system diseases[mh] OR nervous system physiological phenomena[mh] OR Neurogranin[mh] OR Oligodendroglia[mh] OR Peroxisome Proliferator-Activated Receptors[mh] OR Psychological Phenomena and Processes[mh] OR Receptors, thyroid hormone[mh] OR Receptors, thyrotropin[mh] OR Retinoid X Receptors[mh] OR thyroid diseases[mh] OR thyroid hormones[mh] OR Thyrotropinreleasing hormone[mh] OR Thyroxine-Binding Proteins[mh] OR Pregnane X Receptor[supplementary concept] OR thyroid-hormone-receptor interacting protein[supplementary concept] OR Constitutive androstane receptor[supplementary concept] OR Academic performance[tiab] OR auditory[tiab] OR cortical[tiab] OR delayed development[tiab] OR developmental impairment[tiab] OR developmentaldelay*[tiab] OR developmental-disorder*[tiab] OR euthyroid[tiab] OR gait[tiab] OR glia*[tiab] OR gliogenesis[tiab] OR hyperactiv*[tiab] OR impulse-control[tiab] OR iodide peroxidase[tiab] OR IQ[tiab] OR ischemi*[tiab] OR locomotor[tiab] OR mental deficiency[tiab] OR mental development[tiab] OR mental illness[tiab] OR mental-deficit[tiab] OR mobility[tiab] OR mood[tiab] OR morris-maze[tiab] OR morris-water[tiab] OR motor abilit*[tiab] OR Motor activities[tiab] OR motor performance[tiab] OR nerve[tiab] OR neural[tiab] OR neurobehav*[tiab] OR Neurocognitive impairment[tiab] OR neurodegenerat*[tiab] OR Neurodevelopment*[tiab] OR neurodisease*[tiab] OR neurologic*[tiab] OR neuromuscular[tiab] OR neuron*[tiab] OR neuropath*[tiab] OR obsessive compulsive[tiab] OR OCD[tiab] OR olfaction[tiab] OR olfactory[tiab] OR open-field-test[tiab] OR passive avoidance[tiab] OR plasticity[tiab] OR senil*[tiab] OR sociab*[tiab] OR speech*[tiab] OR spelling[tiab] OR stereotypic-movement*[tiab] OR synap*[tiab] OR tauopath*[tiab] OR Thyroglobulin[tiab] OR Thyroid disease*[tiab] OR thyroid gland[tiab] OR thyroid hormone*[tiab] OR thyronine*[tiab] OR visual motor[tiab] OR Visuospatial processing[tiab] OR water maze[tiab]) OR ((active-avoidance[tiab] OR ADHD[tiab] OR alzheimer*[tiab] OR amygdala[tiab] OR antisocial[tiab] OR anxiety[tiab] OR anxious[tiab] OR asperger*[tiab] OR attention deficit[tiab] OR autism[tiab] OR autistic[tiab] OR behavioral[tiab] OR behaviors[tiab] OR behavioural[tiab] OR behaviours[tiab] OR bipolar[tiab] OR cerebellum[tiab] OR cognition[tiab] OR cognitive[tiab] OR communicationdisorder*[tiab] OR comprehension[tiab] OR cranial[tiab] OR dementia[tiab] OR dendrit*[tiab] OR dentate-gyrus[tiab] OR depression[tiab] OR dextrothyroxine[tiab] OR diiodothyronine*[tiab] OR diiodotyrosine[tiab] OR down syndrome[tiab] OR dyslexia[tiab] OR entorhinal cortex[tiab] OR epilep*[tiab] OR gangli*[tiab] OR goiter[tiab] OR graves-disease[tiab] OR hearing[tiab] OR hippocamp*[tiab] OR human development[tiab] OR hyperthyroid*[tiab] OR hypothalam*[tiab] OR hypothyroid*[tiab] OR impulsiv*[tiab] OR Intellectual disability[tiab] OR intelligence[tiab] OR language[tiab] OR learning[tiab] OR lewy bod*[tiab] OR long-term potentiation[tiab] OR long-term synaptic depression[tiab] OR memory[tiab] OR mental disorder*[tiab] OR mental recall[tiab] OR monoiodotyrosine[tiab] OR Motor activity[tiab] OR motor skill*[tiab] OR multiple sclerosis[tiab] OR myxedema[tiab] OR Nervous system[tiab] OR nervous-system[tiab] OR neurit*[tiab] OR optic[tiab] OR palsy[tiab] OR panic[tiab] OR parahippocamp*[tiab] OR paranoia[tiab] OR paranoid[tiab] OR parkinson*[tiab] OR perception[tiab] OR perforant*[tiab] OR personality[tiab] OR phobia[tiab] OR problem solving[tiab] OR proprioception[tiab] OR psychomotor[tiab] OR reflex[tiab] OR risk taking[tiab] OR schizophrenia[tiab] OR seizure*[tiab] OR sensation*[tiab] OR sleep[tiab] OR smell[tiab] OR spatial behavior[tiab] OR stroke[tiab] OR substantia-nigra[tiab] OR taste[tiab] OR thyroiditis[tiab] OR thyrotoxicosis[tiab] OR Thyrotropin[tiab] OR thyroxine[tiab] OR triiodothyronine[tiab] OR vision[tiab]) NOT medline[sb])).

[10] The epidemiology data were fully assessed, while the animal and mechanistic literature were scanned for potentially major advances that might impact the confidence conclusions, but this effort did not find significant evidence of increased understanding of how fluoride may affect children’s cognitive neurodevelopment and did not strengthen the confidence assessment based on the human evidence available in 2020. In early drafts, it was apparent that the animal data were of poor quality and that the human data were most informative and would be the basis of the confidence conclusions. Therefore, findings from the animal evidence stream were determined to be inadequate and were removed from further drafts.

[11] MeSH heading.