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Neurotox Res. 2018 Nov;34(4):781-798. doi: 10.1007/s12640-018-9870-x. Epub 2018 Feb 5.

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

Author information

1
Neurotoxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Mail Drop C1-04, P.O. Box 12233, Research Triangle Park, NC, 27709, USA.
2
Social & Scientific Systems, Inc, Durham, NC, 27703, USA.
3
Cellular & Molecular Pathology Branch, Division of the National Toxicology Program, NIEHS, Research Tringle Park, NC, 27709, USA.
4
Experimental Pathology Laboratories, Research Triangle Park, NC, USA.
5
Charles River Laboratories, Inc, Durham, NC, USA.
6
Neurotoxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Mail Drop C1-04, P.O. Box 12233, Research Triangle Park, NC, 27709, USA. harry@niehs.nih.gov.

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-.

KEYWORDS:

Activity; Avoidance; Fluoride; Learning and memory; Neurodevelopment

PMID:
29404855
PMCID:
PMC6077107
DOI:
10.1007/s12640-018-9870-x
[Indexed for MEDLINE]
Free PMC Article

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