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An Evaluation of Neurotoxicity Following Fluoride Exposure from Gestational Through Adult Ages in Long-Evans Hooded Rats.

ABSTRACT: At elevated levels, fluoride (F^-) exposure has been associated with adverse human health effects. In rodents, F^- exposure has been reported to induce deficits in motor performance and learning and memory. In this study, we examined Long-Evans hooded male rats maintained on a standard diet (20.5 ppm F^-) or a low F^- diet (3.24 ppm F^-) with drinking water exposure to 0, 10, or 20 ppm F^- from gestational day 6 through adulthood. At postnatal day 25, brain F^- levels were 0.048 or 0.081 μg/g and femur 235 or 379.8 μg/g for 10 and 20 ppm F^-, respectively. Levels increase with age and in adults, levels for plasma were 0.036 or 0.025 μg/ml; for the brain 0.266 or 0.850 μg/g; and for the femur, 681.2 or 993.4 μg/g. At these exposure levels, we observed no exposure-related differences in motor, sensory, or learning and memory performance on running wheel, open-field activity, light/dark place preference, elevated plus maze, pre-pulse startle inhibition, passive avoidance, hot-plate latency, Morris water maze acquisition, probe test, reversal learning, and Y-maze. Serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels were not altered as a function of 10 or 20 ppm F^- in the drinking water. No exposure-related pathology was observed in the heart, liver, kidney, testes, seminal vesicles, or epididymides. Mild inflammation in the prostate gland was observed at 20 ppm F^-. No evidence of neuronal death or glial activation was observed in the hippocampus at 20 ppm F^-.

SUBMITTER: McPherson CA

PROVIDER: S-EPMC6077107 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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An Evaluation of Neurotoxicity Following Fluoride Exposure from Gestational Through Adult Ages in Long-Evans Hooded Rats.

McPherson Christopher A CA Zhang Guozhu G Gilliam Richard R Brar Sukhdev S SS Wilson Ralph R Brix Amy A Picut Catherine C Harry G Jean GJ

Neurotoxicity research 20180205 4

At elevated levels, fluoride (F-) exposure has been associated with adverse human health effects. In rodents, F- exposure has been reported to induce deficits in motor performance and learning and memory. In this study, we examined Long-Evans hooded male rats maintained on a standard diet (20.5 ppm F-) or a low F- diet (3.24 ppm F-) with drinking water exposure to 0, 10, or 20 ppm F- from gestational day 6 through adulthood. At po ...[more]

PMID: 29404855

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Project description:BackgroundFluoride has been associated with IQ deficits during early brain development, but the period in which children are most sensitive is unknown.ObjectiveWe assessed effects of fluoride on IQ scores across prenatal and postnatal exposure windows.MethodsWe used repeated exposures from 596 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals pregnancy and birth cohort. Fluoride was measured in urine (mg/L) collected from women during pregnancy and in their children between 1.9 and 4.4 years; urinary fluoride was adjusted for specific gravity. We estimated infant fluoride exposure (mg/day) using water fluoride concentration and duration of formula-feeding over the first year of life. Intelligence was assessed at 3-4 years using the Wechsler Preschool and Primary Scale of Intelligence-III. We used generalized estimating equations to examine the associations between fluoride exposures and IQ, adjusting for covariates. We report results based on standardized exposures given their varying units of measurement.ResultsThe association between fluoride and performance IQ (PIQ) significantly differed across prenatal, infancy, and childhood exposure windows collapsing across child sex (p = .001). The strongest association between fluoride and PIQ was during the prenatal window, B = -2.36, 95% CI: -3.63, -1.08; the association was also significant during infancy, B = -2.11, 95% CI: -3.45, -0.76, but weaker in childhood, B = -1.51, 95% CI: -2.90, -0.12. Within sex, the association between fluoride and PIQ significantly differed across the three exposure windows (boys: p = .01; girls: p = .01); among boys, the strongest association was during the prenatal window, B = -3.01, 95% CI: -4.60, -1.42, whereas among girls, the strongest association was during infancy, B = -2.71, 95% CI: -4.59, -0.83. Full-scale IQ estimates were weaker than PIQ estimates for every window. Fluoride was not significantly associated with Verbal IQ across any exposure window.ConclusionAssociations between fluoride exposure and PIQ differed based on timing of exposure. The prenatal window may be critical for boys, whereas infancy may be a critical window for girls.

Dataset Information

An Evaluation of Neurotoxicity Following Fluoride Exposure from Gestational Through Adult Ages in Long-Evans Hooded Rats.

Publications

An Evaluation of Neurotoxicity Following Fluoride Exposure from Gestational Through Adult Ages in Long-Evans Hooded Rats.

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