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

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


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.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / growth & development
  • Brain / metabolism
  • Brain / pathology
  • Environmental Exposure*
  • Female
  • Femur / drug effects
  • Femur / growth & development
  • Femur / metabolism
  • Fluorides / metabolism
  • Fluorides / toxicity*
  • Learning / drug effects
  • Male
  • Memory / drug effects
  • Motor Activity / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Prostate / drug effects
  • Prostate / growth & development
  • Prostate / metabolism
  • Prostate / pathology
  • Random Allocation
  • Rats, Long-Evans
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood


  • Triiodothyronine
  • Thyrotropin
  • Thyroxine
  • Fluorides