Editing Sugar substitute (section)

===Saccharin===
{{Main|Saccharin}}
[[File:Süßstoff Saccharin Zucker-Museum.jpg|thumb|right|200px|Saccharin, historical wrapping – [[Sugar Museum (Berlin)|Sugar Museum, Berlin]]]]
Apart from [[sugar of lead]] (used as a sweetener in ancient through medieval times before the toxicity of lead was known), saccharin was the first artificial sweetener and was originally synthesized in 1879 by Remsen and Fahlberg. Its sweet taste was discovered by accident. It had been created in an experiment with toluene derivatives. A process for the creation of saccharin from [[phthalic anhydride]] was developed in 1950, and, currently, saccharin is created by this process as well as the original process by which it was discovered. It is 300 to 500 times sweeter than sucrose and is often used to improve the taste of toothpastes, dietary foods and dietary beverages. The bitter aftertaste of saccharin is often minimized by blending it with other sweeteners.

Fear about saccharin increased when a 1960 study showed that high levels of saccharin may cause [[bladder cancer]] in laboratory rats. In 1977, [[Canada]] banned saccharin as a result of the animal research. In the United States, the FDA considered banning saccharin in 1977, but Congress stepped in and placed a moratorium on such a ban. The moratorium required a warning label and also mandated further study of saccharin safety.

Subsequently, it was discovered that saccharin causes cancer in male rats by a mechanism not found in humans. At high doses, saccharin causes a precipitate to form in rat urine. This precipitate damages the cells lining the bladder (urinary bladder urothelial [[cytotoxicity]]) and a [[tumor]] forms when the cells regenerate (regenerative hyperplasia). According to the [[International Agency for Research on Cancer]], part of the [[World Health Organization]], "This mechanism is not relevant to humans because of critical interspecies differences in urine composition".<ref>{{Cite book |url=https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Some-Chemicals-That-Cause-Tumours-Of-The-Kidney-Or-Urinary-Bladder-In-Rodents-And-Some-Other-Substances-1999 |title=IARC Monograohs on the Evaluation of Carcinogenic Risks to Humans: Some Chemicals that Cause Tumours of the Kidney or Urinary Bladder in Rodents and Some Other Substances |publisher=[[International Agency for Research on Cancer]] |year=1999 |isbn=978-92-832-1273-7 |volume=73 |location=Lyon, France |pages=607}}</ref>

In 2001, the United States repealed the warning label requirement, while the threat of an FDA ban had already been lifted in 1991. Most other countries also permit saccharin, but restrict the levels of use, while other countries have outright banned it.

The EPA has removed saccharin and its salts from their list of hazardous constituents and commercial chemical products. In a 14 December 2010 release, the EPA stated that saccharin is no longer considered a potential hazard to human health.