Excess<unk>  consumption has been studied as a factor in the following: Brain Some research has suggested that high levels of<unk>  exposure may adversely affect neurodevelopment in children, but the evidence is of insufficient quality to allow any firm conclusions to be drawn. Bones Whilst<unk> ted water is associated with decreased levels of fractures in a population, toxic levels of<unk>  have been associated with a weakening of bones and an increase in hip and wrist fractures. The U.S. National Research Council concludes that fractures with<unk>  levels 1–4 mg/L, suggesting a dose-response relationship, but states that there is "suggestive but inadequate for drawing firm conclusions about the risk or safety of exposures at 2 mg/L". Consumption of<unk>  at levels beyond those used in<unk> ted water for a long period of time causes skeletal fluorosis. In some areas, particularly the Asian subcontinent, skeletal fluorosis is endemic. It is known to cause irritable-bowel symptoms and joint pain. Early stages are not clinically obvious, and may be misdiagnosed as (seronegative) rheumatoid arthritis or ankylosing spondylitis. Kidney<unk>  induced nephrotoxicity is kidney injury due to toxic levels of serum<unk> , commonly due to release of<unk>  from<unk> -containing drugs, such as methoxyflurane. Within the recommended dose, no effects are expected, but chronic ingestion in excess of 12 mg/day are expected to cause adverse effects, and an intake that high is possible when<unk>  levels are around 4 mg/L. Those with impaired kidney function are more susceptible to adverse effects. The kidney injury is characterised by failure to concentrate urine, leading to polyuria, and subsequent dehydration with hypernatremia and hyperosmolarity. Inorganic<unk>  inhibits adenylate cyclase activity required for antidiuretic hormone effect on the distal convoluted tubule of the kidney.<unk>  also stimulates intrarenal vasodilation, leading to increased medullary blood flow, which interferes with the counter current mechanism in the kidney required for concentration of urine.<unk>  induced nephrotoxicity is dose dependent, typically requiring serum<unk>  levels exceeding 50 micromoles per liter (about 1 ppm) to cause clinically significant renal dysfunction, which is likely when the dose of methoxyflurane exceeds 2.5 MAC hours. (Note: "MAC hour" is the multiple of the minimum alveolar concentration (MAC) of the anesthetic used times the number of hours the drug is administered, a measure of the dosage of inhaled anesthetics.) Elimination of<unk>  depends on glomerular filtration rate. Thus, patients with chronic kidney disease will maintain serum<unk>  for longer period of time, leading to increased risk of<unk>  induced nephrotoxicity. Teeth The only generally accepted adverse effect of<unk>  at levels used for water<unk> tion is dental fluorosis, which can alter the appearance of children's teeth during tooth development; this is mostly mild and usually only an aesthetic concern. Compared to unfluoridated water,<unk> tion to 1 mg/L is estimated to cause fluorosis in one of every 6 people (range 4–21), and to cause fluorosis of aesthetic concern in one of every 22 people (range 13.6–∞). Thyroid<unk> 's suppressive effect on the thyroid is more severe when iodine is deficient, and<unk>  is associated with lower levels of iodine. Thyroid effects in humans were associated with<unk>  levels 0.05–0.13 mg/kg/day when iodine intake was adequate and 0.01–0.03 mg/kg/day when iodine intake was inadequate. Its mechanisms and effects on the endocrine system remain unclear. Testing on mice shows that the medication gamma-Aminobutyric acid (GABA) can be used to treat<unk>  of the thyroid and return normal function. Effects on aquatic organisms<unk>  accumulates in the bone tissues of fish and in the exoskeleton of aquatic invertebrates. The mechanism of<unk>  in aquatic organisms is believed to involve the action of<unk>  ions as enzymatic poisons. In soft waters with low ionic content, invertebrates and fishes may suffer adverse effects from<unk>  concentration as low as 0.5 mg/L. Negative effects are less in hard waters and seawaters, as the bioavailability of<unk>  ions is reduced with increasing water hardness Seawater contains<unk>  at a concentration of 1.3 mg/L.
Fluoride toxicity
Fluorine deficiency
Chromium toxicity
Copper toxicity
Boron deficiency 
Lead poisoning
Zinc toxicity
Chromium deficiency