General Description
White crystals. Odorless or faintly aromatic odor. Sweet taste.
Reactivity Profile
An amide. Acid to litmus. pH of 0.35% aqueous solution: 2.0. Organic amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).
Air & Water Reactions
Slightly soluble in water.
Hazard
A questionable carcinogen. Products con-
taining it must have a warning label.
Potential Exposure
The information provided has to do,
primarily, with the manufacturing of saccharin. Saccharin
has been used as a nonnutritive sweetening agent. At one
point the United States consumption pattern for all forms
of saccharin has been estimated as 45% in soft drinks; 18%
in tabletop sweeteners; 14% in fruits, juices, sweets, chew-
ing gum, and jellies; 10% in cosmetics and oral hygiene
products; 7% in drugs, such as coating on pills; 2% in
tobacco; 2% in electroplating; and 2% for miscellaneous
uses. Human exposure to saccharin occurs primarily
through ingestion because of its use in many dietic foods
and drinks and some personal hygiene products, including
toothpastes and mouthwashes. The general public is
exposed to saccharin, especially by persons required to
reduce sugar intake.
Fire Hazard
Flash point data for this chemical are not available; however, SACCHARIN (MANUFACTURING) is probably combustible.
First aid
If this chemical gets into the eyes, remove any
contact lenses at once and irrigate immediately for at least
15 minutes, occasionally lifting upper and lower lids. Seek
medical attention immediately. If this chemical contacts the skin, remove contaminate skin, remove contaminated clothing and wash immediately
with soap and water. Seek medical attention immediately.
If this chemical has been inhaled, remove from exposure,
begin rescue breathing (using universal precautions, includ-
ing resuscitation mask) if breathing has stopped and
cardiopulmonary resuscitation (CPR) if heart action has
stopped. Transfer promptly to a medical facility.
Shipping
UN3077 Environmentally hazardous substances,
solid, n.o.s., Hazard class: 9; Labels: 9-Miscellaneous haz-
ardous material, Technical Name Required.
Incompatibilities
Dust may form explosive mixture with
air. Incompatible with strong oxidizers (chlorates, nitrates,
peroxides, permanganates, perchlorates, chlorine, bromine,
fluorine, etc.); contact may cause fires or explosions. Keep
away from alkaline materials, strong bases, strong acids,
oxoacids, and epoxides.
Chemical Properties
Saccharin is a crystalline solid with a sweet taste
(500 times sweeter than sugar).
Chemical Properties
Saccharin occurs as odorless white crystals or a white crystalline
powder. It has an intensely sweet taste, with a metallic or bitter
aftertaste that at normal levels of use can be detected by
approximately 25% of the population. The aftertaste can be
masked by blending saccharin with other sweeteners.
Chemical Properties
white crystalline solid
Waste Disposal
Consult with environmental
regulatory agencies for guidance on acceptable disposal
practices. Generators of waste containing this contami-
nant (≥100 kg/mo) must conform to EPA regulations
governing storage, transportation, treatment, and waste
disposal.
Definition
A
white crystalline organic compound used
as an artificial sweetener; it is about 550
times as sweet as sugar (sucrose). It is
nearly insoluble in water and so generally
used in the form of its sodium salt. Possible
links with cancer in animals has restricted
its use in some countries.
Definition
ChEBI: A 1,2-benzisothiazole having a keto-group at the 3-position and two oxo substituents at the 1-position. It is used as an artificial sweetening agent.
Definition
saccharin: A white crystalline solid,C7H5NO3S, m.p. 224°C. It is madefrom a compound of toluene, derivedfrom petroleum or coal tar. It is awell-known artificial sweetener,being some 500 times as sweet assugar (sucrose), and is usually marketedas its sodium salt. Because ofan association with cancer in laboratoryanimals, its use is restricted insome countries.
Preparation
Saccharin is synthesized using two methods: the Remsen-Fahlberg process and the Maumee or Sherwin-Williams method. The Remsen-Fahlberg synthesis of saccharin starts by reacting toluene with chlorosulfonic acid to give ortho and para forms of toluene-sulfonic acid (Figure 78.1). The acid can be converted to sulfonyl chlorides by treating with phosphorus pentachloride. The ortho form, o-toluene-sulfonyl chloride, is treated with ammonia to give o-toluene-sulfonamide, which is then oxidized with potassium permanganate to produce o-sulfamido-benzoic acid. On heating, the latter yields saccharin. Another synthesis was developed at Maumee Chemical Company in Toledo, Ohio, and it came to be known as the Maumee process. This process starts with phthalic anhydride, which is converted into anthranilic acid. Anthranilic acid is then reacted with nitrous acid, sulfur dioxide, chlorine, and ammonia to give saccharin. The Maumee process was further refi ned by the Sherwin-Williams Company and is therefore now referred to as the Sherwin-Williams process.
Production Methods
Saccharin is prepared from toluene by a series of reactions known as the Remsen–Fahlberg method. Toluene is first reacted with chlorosulfonic acid to form o-toluenesulfonyl chloride, which is reacted with ammonia to form the sulfonamide. The methyl group is then oxidized with dichromate, yielding o-sulfamoylbenzoic acid, which forms the cyclic imide saccharin when heated.
An alternative method involves a refined version of the Maumee process. Methyl anthranilate is initially diazotized to form 2- carbomethoxybenzenediazonium chloride; sulfonation followed by oxidation then yields 2-carbomethoxybenzenesulfonyl chloride. Amidation of this material, followed by acidification, forms insoluble acid saccharin.
Brand name
Sweeta (Bristol-Myers Squibb).
Flammability and Explosibility
Nonflammable
Pharmaceutical Applications
Saccharin is an intense sweetening agent used in beverages, food
products, table-top sweeteners, and oral hygiene products such as
toothpastes and mouthwashes. In oral pharmaceutical formulations,
it is used at a concentration of 0.02–0.5% w/w. It has been
used in chewable tablet formulations as a sweetening agent.
Saccharin has been used to form various pharmaceutical cocrystals.
Saccharin can be used to mask some unpleasant taste characteristics
or to enhance flavor systems. Its sweetening power is
approximately 300–600 times that of sucrose.
Biochem/physiol Actions
A sweet tastant for mammals. A glycerol taste receptor binding site specific for glucose has been proposed in drosophila.
Safety Profile
Confirmed carcinogen withexperimental neoplastigenic and tumorigenic data. Mildacute toxicity by ingestion. Experimental teratogenic andreproductive effects. Mutation data reported. Whenheated to decomposition it emits toxic NOx and SOx.
Safety
There has been considerable controversy concerning the safety of
saccharin, which has led to extensive studies since the mid-1970s.
Two-generation studies in rats exposed to diets containing
5.0–7.5% total saccharin (equivalent to 175 g daily in humans)
suggested that the incidence of bladder tumors was significantly
greater in saccharin-treated males of the second generation than in
controls. Further experiments in rats suggested that a contaminant
of commercial saccharin, o-toluene sulfonamide, might
also account for carcinogenic effects. In view of these studies, a ban
on the use of saccharin was proposed in several countries. However,
in 1977 a ban by the FDA led to a Congressional moratorium that
permitted the continued use of saccharin in the USA.
From the available data it now appears that the development of
tumors is a sex-, species-, and organ-specific phenomenon, and
extensive epidemiological studies have shown that saccharin intake
is not related to bladder cancer in humans.
The WHO has set a temporary acceptable daily intake for
saccharin, including its calcium, potassium, and sodium salts, at up
to 2.5 mg/kg body-weight. In the UK, the Committee on Toxicity
of Chemicals in Food, Consumer Products, and the Environment
(COT) has set an acceptable daily intake for saccharin and its
calcium, potassium, and sodium salts (expressed as saccharin
sodium) at up to 5 mg/kg body-weight.
Adverse reactions to saccharin, although relatively few in
relation to its widespread use, include: urticaria with pruritus
following ingestion of saccharin-sweetened beverages and
photosensitization reactions.
LD50 (mouse, oral): 17.5 g/kg
LD50 (rat, IP): 7.10 g/kg
LD50 (rat, oral): 14.2 g/kg
storage
Saccharin is stable under the normal range of conditions employed
in formulations. In the bulk form it shows no detectable
decomposition and only when it is exposed to a high temperature
(125°C) at a low pH (pH 2) for over 1 hour does significant
decomposition occur. The decomposition product formed is
(ammonium-o-sulfo)benzoic acid, which is not sweet. The
aqueous stability of saccharin is excellent.
Saccharin should be stored in a well-closed container in a dry
place.
Purification Methods
Purify saccharin by recrystallisation from Me2CO [solubility 7.14% at 0o, 14.4% at 50o], or aqueous isoPrOH to give a fluorescent solution. It sublimes in vacuo. It is an artificial sweetner and is 500 times sweeter than sucrose. [DeGarmo et al. J Am Pharm Assoc (Sci Ed) 41 17 1952, Beilstein 27 H 168, 870, 27 I 266, 27 II 214, 27 III/IV 2649.]
Regulatory Status
Accepted for use as a food additive in Europe. Note that the EU
number ‘E954’ is applied to both saccharin and saccharin salts.
Included in the FDA Inactive Ingredients Database (oral solutions,
syrups, tablets, and topical preparations). Included in nonparenteral
medicines licensed in the UK. Included in the Canadian List of
Acceptable Non-medicinal Ingredients.
