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 ug/g and femur 235 or 379.8 ug/g for 10 and 20 ppm F^–, respectively. Levels increase with age and in adults, levels for plasma were 0.036 or 0.025 ug/ml; for the brain 0.266 or 0.850 ug/g; and for the femur, 681.2 or 993.4 ug/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^–.