It has also been estimated that optimal water fluoridation for the prevention of dental caries increases the prevalence of dental fluorosis by 4 to 5%. The observed effects are mild to moderate, usually of minimal aesthetic concern. Reports have claimed that water fluoridation can be linked to the development of osteoporosis and various cancers; however, a recent systematic review has found no evidence to support these claims. Consumption of large amounts of fluoride can lead to fluoride poisoning and death; the lethal dose for most adult humans is estimated at 5 to 10 g (which is equivalent to 32 to 64 mg elemental fluoride/kg body weight). Ingestion of fluoride can produce gastrointestinal discomfort at doses at least 15 to 20 times lower (0.2–0.3 mg/kg) than lethal doses. Chronic intake and topical exposure may cause dental fluorosis, and excess systematic exposure can lead to systemic effects such as skeletal fluorosis. Young children are at risk for receiving excess fluoride, and the American Dental Association (ADA) has recently issued an interim guidance on their fluoride consumption. In 1974 a three-year-old child swallowed 45 milliliters of 2% fluoride solution, estimated to be triple the fatal amount, and then died. The fluoride was administered during his first visit to the dentist, and the dental office was later found liable for the death. Strictly speaking, fluoride therapy repairs rather than prevents damage to the teeth, causing the mineral fluorapatite to be incorporated into damaged tooth enamel. Fluorapatite is not a natural component of human teeth, although it is found in the teeth of sharks. The main mineral found in natural tooth enamel is hydroxyapatite rather than the fluorapatite created in the presence of fluoride. Even without fluoride, teeth experience alternating increases and decreases in mineral content, depending upon how acidic or alkaline the mouth is, and depending upon the concentration of other substances in the mouth, such as phosphate and calcium. Fluoride reduces the decay of tooth enamel by the formation of fluorapatite and its incorporation into the dental enamel. The fluoride ions reduce the rate of tooth enamel demineralization and increase the rate of remineralization of teeth at the early stages of cavities. Fluoride exerts these effects by the demineralization and remineralization cycle. The remineralization cycle, critical to decay prevention, occurs when fluoride is present in the oral cavity. After fluoride is swallowed it has a minimal effect.