modern pharmaceuticals contain fluorine. These organofluorine compounds are not sources of fluoride poisoning. The carbon–fluorine bond is too strong to release fluoride. Fluoride in toothpaste Children may experience gastrointestinal distress upon ingesting excessive amounts of flavored toothpaste. Between 1990 and 1994, over 628 people, mostly children, were treated after ingesting too much fluoride-containing toothpaste. "While the outcomes were generally not serious," gastrointestinal symptoms appear to be the most common problem reported. However given the low concentration of fluoride present in dental products, this is potentially due to consumption of other major components. Fluoride in drinking water Around one-third of the world's population drinks water from groundwater resources. Of this, about 10 percent, approximately 300 million people, obtains water from groundwater resources that are heavily contaminated with arsenic or fluoride. These trace elements derive mainly from leaching of minerals. Maps are available of locations of potential problematic wells via the Groundwater Assessment Platform (GAP). Effects Excess fluoride consumption has been studied as a factor in the following: Brain Some research has suggested that high levels of fluoride exposure may adversely affect neurodevelopment in children, but the evidence is of insufficient quality to allow any firm conclusions to be drawn. Bones Whilst fluoridated water is associated with decreased levels of fractures in a population, toxic levels of fluoride 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 fluoride 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 fluoride at levels beyond those used in fluoridated 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 Fluoride induced nephrotoxicity is kidney injury due to toxic levels of serum fluoride, commonly due to release of fluoride from fluorine-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 fluoride levels are around 4 mg/L. Those with impaired kidney function are more susceptible to