Saccharin

Last updated
Saccharin [1] [2]
Saccharin.svg
Saccharin-from-xtal-3D-balls.png
Names
Preferred IUPAC name
1H-1λ6,2-Benzothiazole-1,1,3(2H)-trione
Other names
  • ortho-benzoic sulfimide
  • ortho sulphobenzimide
[3]
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.001.202 OOjs UI icon edit-ltr-progressive.svg
E number E954 (glazing agents, ...)
KEGG
PubChem CID
UNII
  • InChI=1S/C7H5NO3S/c9-7-5-3-1-2-4-6(5)12(10,11)8-7/h1-4H,(H,8,9) Yes check.svgY
    Key: CVHZOJJKTDOEJC-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C7H5NO3S/c9-7-5-3-1-2-4-6(5)12(10,11)8-7/h1-4H,(H,8,9)
    Key: CVHZOJJKTDOEJC-UHFFFAOYAR
  • O=C2c1ccccc1S(=O)(=O)N2
Properties
C7H5NO3S
Molar mass 183.18 g·mol−1
AppearanceWhite crystalline solid
Density 0.828 g/cm3
Melting point 228.8 to 229.7 °C (443.8 to 445.5 °F; 501.9 to 502.8 K)
1 g per 290 mL
Acidity (pKa)1.6 [4]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Saccharin, also called saccharine, benzosulfimide, or E954, or used in saccharin sodium or saccharin calcium forms, is a non-nutritive artificial sweetener. [1] [5] Saccharin is a benzoic sulfimide that is about 500 times sweeter than sucrose, but has a bitter or metallic aftertaste, especially at high concentrations. [1] It is used to sweeten products, such as drinks, candies, baked goods, tobacco products, excipients, and for masking the bitter taste of some medicines. [1] [5] It appears as white crystals and is odorless. [1]

Contents

Etymology

Saccharin derives its name from the word "saccharine", meaning "sugary". The word saccharine is used figuratively, often in a derogative sense, to describe something "unpleasantly over-polite" or "overly sweet". [6] Both words are derived from the Greek word σάκχαρον (sakkharon) meaning "gravel". [7] Similarly, saccharose is an obsolete name for sucrose (table sugar).

Properties

Sodium salt of saccharin, a white powder Saccharin-Na substance photo.jpg
Sodium salt of saccharin, a white powder

Saccharin is heat-stable. [8] It does not react chemically with other food ingredients; as such, it stores well. Blends of saccharin with other sweeteners are often used to compensate for each sweetener's weaknesses and faults. A 10:1 cyclamate–saccharin blend is common in countries where both these sweeteners are legal; in this blend, each sweetener masks the other's offtaste. Saccharin is often used with aspartame in diet carbonated soft drinks, so some sweetness remains should the fountain syrup be stored beyond aspartame's relatively short shelf life.

In its acid form, saccharin is not water-soluble. The form used as an artificial sweetener is usually its sodium salt. [9] The calcium salt is also sometimes used, especially by people restricting their dietary sodium intake. Both salts are highly water-soluble: 0.67 g/ml in water at room temperature. [10] [11]

Safety and health effects

In the 1970s, studies performed on laboratory rats found an association between consumption of high doses of saccharin and the development of bladder cancer. [12] However, further study determined that this effect was due to a mechanism that is not relevant to humans (deposition of crystals; see § History section). [12] Epidemiological studies have shown no evidence that saccharin is associated with bladder cancer in humans. [12] [13] The International Agency for Research on Cancer (IARC) originally classified saccharin in Group 2B ("possibly carcinogenic to humans") based on the rat studies, but downgraded it to Group 3 ("not classifiable as to the carcinogenicity to humans") upon review of the subsequent research. [14]

Saccharin has no food energy and no nutritional value. [15] It is safe to consume for individuals with diabetes or prediabetes. [16] [17]

People with sulfonamide allergies can experience allergic reactions to saccharin, although it has been suggested that this may be due to a general predisposition to allergic reactions rather than a specific cross-reaction between antimicrobial sulfonamides and non-antimicrobial ones (like saccharin). [18] [19] Saccharin in toothpaste can cause burning sensations, swelling, and rashes of the mouth and lips in sensitive individuals. [20]

History

Saccharin, historical wrapping, Sugar Museum (Berlin) Sussstoff Saccharin Zucker-Museum.jpg
Saccharin, historical wrapping, Sugar Museum (Berlin)
1893 ad Saccharine 300 times sweeter than sugar ad, Schulze-Berge, Koechl & Movius sole licenses in the U. S. A., selling agents wanted for the Pacific Coast - Pacific wine and spirit review (IA pacificwinespiri29sanfrich) (page 10 crop).jpg
1893 ad

Saccharin was produced first in 1879, by Constantin Fahlberg, a chemist working on coal tar derivatives in Ira Remsen's laboratory at Johns Hopkins University. [21] Fahlberg noticed a sweet taste on his hand one evening, and connected this with the compound benzoic sulfimide on which he had been working that day. [22] [23] Fahlberg and Remsen published articles on benzoic sulfimide in 1879 and 1880. [10] [24] In 1884, then working on his own in New York City, Fahlberg applied for patents in several countries, describing methods of producing this substance that he named saccharin. [25] Two years later, he began production of the substance in a factory in a suburb of Magdeburg in Germany. Fahlberg would soon grow wealthy, while Remsen merely grew irritated, believing he deserved credit for substances produced in his laboratory. On the matter, Remsen commented, "Fahlberg is a scoundrel. It nauseates me to hear my name mentioned in the same breath with him." [26]

Although saccharin was commercialized not long after its discovery, until sugar shortages during World War I, its use had not become widespread. Its popularity further increased during the 1960s and 1970s among dieters, since saccharin is a calorie-free sweetener. In the United States, saccharin is often found in restaurants in pink packets; the most popular brand is "Sweet'n Low".

Because of the difficulty of importing sugar from the West Indies, the British Saccharin Company was founded in 1917 to produce saccharin at its Paragon Works near Accrington, Lancashire. Production was licensed and controlled by the Board of Trade in London. Production continued on the site until 1926.

Government regulation

Starting in 1907, the United States Food and Drug Administration began investigating saccharin as a result of the Pure Food and Drug Act. Harvey Wiley, then the director of the bureau of chemistry for the FDA, viewed it as an illegal substitution of a valuable ingredient, sugar, by a less valuable ingredient. In a clash that had career consequences, Wiley told President Theodore Roosevelt, "Everyone who ate that sweet corn was deceived. He thought he was eating sugar, when in point of fact he was eating a coal tar product totally devoid of food value and extremely injurious to health." But Roosevelt himself was a consumer of saccharin, and, in a heated exchange, Roosevelt angrily answered Wiley by stating, "Anybody who says saccharin is injurious to health is an idiot." The episode proved the undoing of Wiley's career. [27]

In 1911, Food Inspection Decision 135 stated that foods containing saccharin were adulterated. [28] However, in 1912, Food Inspection Decision 142 stated that saccharin was not harmful. [29]

More controversy was stirred in 1969 with the discovery of files from the FDA's investigations of 1948 and 1949. These investigations, which had originally argued against saccharin use, were shown to prove little about saccharin being harmful to human health.[ citation needed ] In 1977, the FDA made an attempt to completely ban the substance, [11] [30] following studies showing that the substance caused bladder cancer in rats. The attempted ban was unsuccessful due to public opposition that was encouraged by industry advertisements, [30] and instead the following label was mandated: "Use of this product may be hazardous to your health. This product contains saccharin which has been determined to cause cancer in laboratory animals". That requirement was dropped in 2000 following new research that concluded humans reacted differently than rats and were not at risk of cancer at typical intake levels. [30] (See also: § Warning label addition and removal below.) The sweetener has continued to be widely used in the United States and is now the third-most popular artificial sweetener behind sucralose and aspartame.

In the European Union, saccharin is also known by the E number (additive code) E954. [31]

The current status of saccharin is that it is allowed in most countries, and countries such as Canada have lifted their previous ban of it as a food additive. [32] The claims that it is associated with bladder cancer were shown to be unfounded in experiments on primates. [33] (It is, however, prohibited to mail saccharin tablets or packets to France. [34] )

Saccharin was formerly on California's list of chemicals known to the state to cause cancer for the purposes of Proposition 65, but it was delisted in 2001. [35]

Warning label addition and removal

In 1958, the United States Congress amended the Food, Drugs, and Cosmetic Act of 1938 with the Delaney clause to mandate that the Food and Drug Administration not approve substances that "induce cancer in man, or, after tests, [are] found to induce cancer in animals." Studies in laboratory rats during the early 1970s linked saccharin with the development of bladder cancer in rodents. As a consequence, all food containing saccharin was labeled with a warning meeting the requirement of the Saccharin Study and Labeling Act of 1977. [36]

However, in 2000, the warning labels were removed because scientists learned that rodents, unlike humans, have a unique combination of high pH, high calcium phosphate, and high protein levels in their urine. [37] [38] One or more of the proteins that are more prevalent in male rats combine with calcium phosphate and saccharin to produce microcrystals that damage the lining of the bladder. Over time, the rat's bladder responds to this damage by overproducing cells to repair the damage, which leads to tumor formation. Since this does not occur in humans, there is no elevated risk of bladder cancer. [39]

The delisting of saccharin led to legislation repealing the warning label requirement for products containing saccharin. [40] In 2001, the U.S. Food and Drug Administration and the state of California reversed their positions on saccharin, declaring it safe for consumption. [30] The FDA's decision followed a 2000 determination by the U.S. Department of Health and Human Services' National Toxicology Program to remove saccharin from its list of carcinogens.

The Environmental Protection Agency has officially removed saccharin and its salts from their list of hazardous constituents and commercial chemical products. In a release in December 2010, the EPA stated that saccharin is no longer considered a potential hazard to human health. [41]

Chemistry

Preparation

Saccharin can be produced in various ways. [42] The original route by Remsen and Fahlberg starts with toluene; another route begins with o-chlorotoluene. [43] Sulfonation of toluene by chlorosulfonic acid gives the ortho and para substituted sulfonyl chlorides. The ortho isomer is separated and converted to the sulfonamide with ammonia. Oxidation of the methyl substituent gives the carboxylic acid, which cyclicizes to give saccharin free acid: [44]

Remsen-Fahlberg synthesis of saccharin.png

In 1950, an improved synthesis was developed at the Maumee Chemical Company of Toledo, Ohio. In this synthesis, the methyl anthranilate successively reacts with nitrous acid (from sodium nitrite and hydrochloric acid), sulfur dioxide, chlorine, and then ammonia to yield saccharin: [44]

Maumee synthesis of saccharin.png

Properties and reactions

The free acid of saccharin has a low pKa of 1.6 (the acidic hydrogen being that attached to the nitrogen). [4] Saccharin can be used to prepare exclusively disubstituted amines from alkyl halides via a nucleophilic substitution, [45] followed by a Gabriel synthesis. [46] [47]

See also

Related Research Articles

<span class="mw-page-title-main">Aspartame</span> Artificial non-saccharide sweetener

Aspartame is an artificial non-saccharide sweetener 200 times sweeter than sucrose and is commonly used as a sugar substitute in foods and beverages. It is a methyl ester of the aspartic acid/phenylalanine dipeptide with brand names NutraSweet, Equal, and Canderel. Aspartame was approved by the US Food and Drug Administration (FDA) in 1974, and then again in 1981, after approval was revoked in 1980.

<span class="mw-page-title-main">Food additive</span> Substances added to food

Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), salt (salting), smoke (smoking), sugar (crystallization), etc. This allows for longer-lasting foods such as bacon, sweets or wines. With the advent of ultra-processed foods in the second half of the twentieth century, many additives have been introduced, of both natural and artificial origin. Food additives also include substances that may be introduced to food indirectly in the manufacturing process, through packaging, or during storage or transport.

<span class="mw-page-title-main">Sucralose</span> Non-nutritive sweetener

Sucralose is an artificial sweetener and sugar substitute. As the majority of ingested sucralose is not metabolized by the body, it adds minimal calories. In the European Union, it is also known under the E number E955. It is produced by chlorination of sucrose, selectively replacing three of the hydroxy groups—in the C1 and C6 positions of the fructose portion and the C4 position of the glucose portion—to give a 1,6-dichloro-1,6-dideoxyfructose–4-chloro-4-deoxygalactose disaccharide. Sucralose is about 600 times sweeter than sucrose, three times as sweet as both aspartame and acesulfame potassium, and twice as sweet as sodium saccharin.

<span class="mw-page-title-main">Sugar substitute</span> Sugarless food additive intended to provide a sweet taste

A sugar substitute is a food additive that provides a sweetness like that of sugar while containing significantly less food energy than sugar-based sweeteners, making it a zero-calorie or low-calorie sweetener. Artificial sweeteners may be derived through manufacturing of plant extracts or processed by chemical synthesis. Sugar substitute products are commercially available in various forms, such as small pills, powders, and packets.

<span class="mw-page-title-main">Cyclamate</span> Chemical compound

Cyclamate is an artificial sweetener. It is 30–50 times sweeter than sucrose, making it the least potent of the commercially used artificial sweeteners. It is often used with other artificial sweeteners, especially saccharin; the mixture of 10 parts cyclamate to 1 part saccharin is common and masks the off-tastes of both sweeteners. It is less expensive than most sweeteners, including sucralose, and is stable under heating. Safety concerns led to it being banned in a few countries, though the European Union considers it safe.

<span class="mw-page-title-main">Neohesperidin dihydrochalcone</span> Chemical compound

Neohesperidin dihydrochalcone, sometimes abbreviated to neohesperidin DC or simply NHDC, is an artificial sweetener derived from citrus.

<span class="mw-page-title-main">Acesulfame potassium</span> Calorie-free sugar substitute

Acesulfame potassium, also known as acesulfame K or Ace K, is a synthetic calorie-free sugar substitute often marketed under the trade names Sunett and Sweet One. In the European Union, it is known under the E number E950. It was discovered accidentally in 1967 by German chemist Karl Clauss at Hoechst AG. In chemical structure, acesulfame potassium is the potassium salt of 6-methyl-1,2,3-oxathiazine-4(3H)-one 2,2-dioxide. It is a white crystalline powder with molecular formula C
4H
4KNO
4S and a molecular weight of 201.24 g/mol.

<span class="mw-page-title-main">Diet soda</span> Type of sugar-free or artificially sweetened soda

Diet or light beverages are generally sugar-free, artificially sweetened beverages with few or no calories. They are marketed for diabetics and other people who want to reduce their sugar and/or caloric intake.

<span class="mw-page-title-main">Tab (drink)</span> Diet cola brand

Tab was a diet cola soft drink produced and distributed by The Coca-Cola Company, introduced in 1963 and discontinued in 2020. The company's first diet drink, Tab was popular among some people throughout the 1960s and 1970s as an alternative to Coca-Cola. Several variations were made, including a number of fruit-flavored, root beer, and ginger ale versions. Caffeine-free and clear variations were released in the late 1980s and early 1990s.

<span class="mw-page-title-main">Neotame</span> Artificial sweetener

Neotame, also known by the trade name Newtame, is a non-caloric artificial sweetener and aspartame analog by NutraSweet. By mass, it is 8000 times sweeter than sucrose. It has no notable off-flavors when compared to sucrose. It enhances original food flavors. It can be used alone, but is often mixed with other sweeteners to increase their individual sweetness and decrease their off-flavors. It is chemically somewhat more stable than aspartame. Its use can be cost effective in comparison to other sweeteners as smaller amounts of neotame are needed.

<span class="mw-page-title-main">Dulcin</span> Chemical compound

Dulcin is an artificial sweetener about 250 times sweeter than sugar, discovered in 1883 by the Polish chemist Józef (Joseph) Berlinerblau. It was first mass-produced about seven years later. Although it was discovered only five years after saccharin, it never enjoyed the latter compound's market success. Nevertheless, it was an important sweetener of the early 20th century and had an advantage over saccharin in that it did not possess a bitter aftertaste.

<span class="mw-page-title-main">Alitame</span> Chemical compound

Alitame is an aspartic acid-containing dipeptide sweetener. It was developed by Pfizer in the early 1980s and currently marketed in some countries under the brand name Aclame. Most dipeptides are not sweet, but the unexpected discovery of aspartame in 1965 led to a search for similar compounds that shared its sweetness. Alitame is one such second-generation dipeptide sweetener. Neotame, developed by the owners of the NutraSweet brand, is another.

<span class="mw-page-title-main">Lactisole</span> Chemical compound

Lactisole is the sodium salt and commonly supplied form of 2-(4-methoxyphenoxy)propionic acid, a natural carboxylic acid found in roasted coffee beans. Like gymnemic acid, it has the property of masking sweet flavors and is used for this purpose in the food industry.

<span class="mw-page-title-main">Sweetness</span> Basic taste

Sweetness is a basic taste most commonly perceived when eating foods rich in sugars. Sweet tastes are generally regarded as pleasurable. In addition to sugars like sucrose, many other chemical compounds are sweet, including aldehydes, ketones, and sugar alcohols. Some are sweet at very low concentrations, allowing their use as non-caloric sugar substitutes. Such non-sugar sweeteners include saccharin, aspartame, sucralose and stevia. Other compounds, such as miraculin, may alter perception of sweetness itself.

Fruit2O, formerly manufactured by Kraft, is a lightly flavored, non-carbonated water beverage introduced in 1999. Fruit2o was introduced to compete not only with the bottled water market but also with the soft drink market. Sunny Delight Beverages purchased the Veryfine Products line from Kraft in 2007.

The artificial sweetener aspartame has been the subject of several controversies since its initial approval by the U.S. Food and Drug Administration (FDA) in 1974. The FDA approval of aspartame was highly contested, beginning with suspicions of its involvement in brain cancer, alleging that the quality of the initial research supporting its safety was inadequate and flawed, and that conflicts of interest marred the 1981 approval of aspartame, previously evaluated by two FDA panels that concluded to keep the approval on hold before further investigation. In 1987, the U.S. Government Accountability Office concluded that the food additive approval process had been followed properly for aspartame. The irregularities fueled a conspiracy theory, which the "Nancy Markle" email hoax circulated, along with claims—counter to the weight of medical evidence—that numerous health conditions are caused by the consumption of aspartame in normal doses.

Gymnemic acids are a class of chemical compounds isolated from the leaves of Gymnema sylvestre (Asclepiadaceae). They are anti-sweet compounds, or sweetness inhibitors. After chewing the leaves, solutions sweetened with sugar taste like water.

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<span class="mw-page-title-main">Saccharin Study and Labeling Act of 1977</span> US law

Saccharin Study and Labeling Act of 1977 or Saccharin Study, Labeling and Advertising Act was a United States federal statute endorsing requirements for a scientific observation regarding the impurities in, potential toxicity, and problematic carcinogenicity of a non-nutritive sweetener better known as saccharin. The Act of Congress invoked an immediate eighteen month moratorium prohibiting the Secretary of Health, Education, and Welfare from pursuing regulatory implications by limiting the production and use of saccharin. The Act codified a warning label requirement advocating the non-nutritive sweetener had been discovered to yield carcinogenicity in laboratory animals.

<span class="mw-page-title-main">Advantame</span> Chemical compound

Advantame is a non-caloric artificial sweetener and aspartame analog by Ajinomoto. By mass, it is about 20,000 times sweeter than sucrose and about 110 times sweeter than aspartame. It has no notable off-flavors when compared to sucrose and tastes sweet a bit longer than aspartame and is chemically more stable. It can be blended with many other natural and artificial sweeteners.

References

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