o-スルホベンズイミド

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Used in Switzerland

log Kow = 0.91

0.91

In dilute aqueous solution it is 500 times as sweet as sugar; sweet taste detectable in 1:100,000 dilution.

Bitter, metallic aftertaste

NON-NUTRITIVE SWEETENER -> FDA Substance added to food

Food

0.828 (NTP, 1992) - Less dense than water; will float

0.828 g/cu cm at 25 °C

This chemical does not meet GHS hazard criteria for 97% (549 of 566) of all reports.

Not Classified

Aggregated GHS information provided per 566 reports by companies from 6 notifications to the ECHA C&L Inventory.

Chemical: 1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide

Commission Regulation No 844/2012

1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 12-12-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/11056

Saccharin: Does not have an individual approval but may be used under an appropriate group standard

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

The food additives saccharin, ammonium saccharin, calcium saccharin, and sodium saccharin may be safely used as sweetening agents in food in accordance with the following conditions /in part 180, section 37/, if the substitution for nutritive sweeteners is for a valid special dietary purpose and is in accord with current special dietary food regulations and policies or if the use or intended use is for an authorized technological purpose other than calorie reduction.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Saccharin is included in weight control drugs.

Toxicity of Food Additives (Excluding Antioxidants), January 1978-July 1989. Govt Reports Announcements & Index (GRA&I) Issue 6 (1990). This bibliography contains citations concerning the toxicity of food additives, incl saccharin, and their effects on the liver, kidneys, bladder, and other organs.

Arnold DL, Boyes BG; The Toxicological Effects Of Saccharin in Short-Term Genotoxicity Assays. Mutat Res 221 (2): 69-132 (1989).

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Saccharin (81-07-2) is delisted as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/append/appb.pdf]

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date 9/29/2006; Reporting date: 11/28/2006.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide is included on this list. Effective date: 9/29/2006; Sunset date: 11/28/2006.

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).

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U202, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

SRP: In bulk storage or manufacturing situations where combustible dusts can collect in sufficient concentrations to give rise to an explosion/deflagration, reasonable precautions shall be taken to reduce or eliminate the hazard. Efforts shall be made to control or eliminate the five elements necessary to initiate a dust explosion. These include combustible dust (fuel), ignition source (heat), oxygen in air (oxidizer), and dispersion of dust particles in sufficient quantity and concentration as well as confinement of the dust cloud. General guidance in these efforts can be found in OSHA's "Combustible Dust in Industry; Preventing and Mitigating the Effects of Fire and Explosions", which list measures to control dusts, eliminate ignition sources, and limit the effects of explosions.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

In 1977, the FDA proposed a ban on saccharin because of the discovery of bladder tumors in some male rats fed with high doses of saccharin. Because no other nonnutritive sweetener was available at that time, the proposed ban faced strong opposition. Legislation to stay the ban has been passed in the U.S. Congress periodically. In December, 1991, the FDA withdrew its proposed ban. All saccharin-containing packaged products were required to carry a warning label indicating that saccharin has been determined to cause cancer in laboratory animals. In 2001, the warning label requirement was lifted by the Congress. In 2003, saccharin was delisted from California Proposition 65 (the so-called carcinogen list).

IT IS NOW WELL ESTABLISHED THAT THE INTERACTION OF MULTIPLE ENVIRONMENTAL FACTORS MAY INCR THE INCIDENCE OF SOME HUMAN CANCERS MORE THAN EXPOSURE TO A SINGLE CARCINOGEN. WITH AN IN VIVO EXPERIMENTAL RAT MODEL, SYNERGISTIC EFFECT IN BLADDER CARCINOGENESIS BETWEEN A SUBCARCINOGENIC DOSE OF THE STRONG BLADDER CARCINOGEN, N-METHYL-N-NITROSOUREA & SACCHARIN WAS DEMONSTRATED.

Since both sodium L-ascorbate and sodium saccharin promote two-stage bladder carcinogenesis in rats, synergism of the two chemicals was investigated with special reference to the role of urinary pH and sodium+ concentration. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for 4 wk and then treated with basal diet containing 5% sodium saccharin, 5% sodium L-ascorbate, 5% sodium saccharin plus 5% sodium L-ascorbate, 5% L-ascorbic acid, 5% sodium saccharin plus 5% L-ascorbic acid, or no added chemical for 32 wk. Treatment with sodium saccharin or sodium L-ascorbate alone significantly increased the induction of neoplastic and preneoplastic lesions of the bladder. Sodium saccharin plus sodium L-ascorbate also induced these bladder lesions significantly when compared with the controls, and the number of lesions was greater than the sum of the lesions in the group treated with sodium saccharin alone or sodium L-ascorbate alone. In contrast, the induction of carcinomas and papillomas in rats treated with sodium saccharin plus sodium L-ascorbate produced an elevation of urinary pH and sodium+ concentrations, although the increases were not different from those in rats fed sodium saccharin or sodium L-ascorbate alone. Sodium saccharin plus L-ascorbic acid, however, did not cause elevation of urinary pH, although it increased urinary sodium+ concentration. Thus, the bladder carcinogenesis promotion by sodium saccharin was synergized by sodium L-ascorbate and inhibited by L-ascorbic acid. This modulation was associated with changes of urinary pH and Na+ concentration. /Sodium saccharin/

CHRONIC RAT FEEDING STUDIES WERE CONDUCTED ON A 10:1 CYCLAMATE/SACCHARIN MIXT. THE TEST MIXT WAS FED AT DIETARY LEVELS DESIGNED TO FURNISH 500, 1120, & 2500 MG/KG TO GROUPS OF 35 MALE & 45 FEMALE RATS. THE ONLY POS FINDING WHICH PROVED TO HAVE CRUCIAL SIGNIFICANCE WAS THE OCCURRENCE OF PAPILLARY CARCINOMAS IN THE BLADDERS OF 12 OF THE 70 RATS FED THE MAX DIETARY LEVEL OF THE MIXT (EQUIV TO ABOUT 2500 MG/KG) FOR PERIODS RANGING FROM 78 TO 105 WK.

N-METHYL-N-NITROSOUREA WAS USED AS INITIATING CARCINOGEN AND GREATLY INCR YIELD OF BLADDER CANCERS IN SACCHARIN TREATED RATS. SACCHARIN IS A WEAK INITIATOR BUT A POWERFUL PROMOTER OF CARCINOGENESIS IN THE RAT BLADDER.

For more Interactions (Complete) data for SACCHARIN (15 total), please visit the HSDB record page.

LC50; Species: Pimephales promelas (fathead minnow, 30 day old); Concentration: 18.3 g/L for 96 hr (confidence limit 16.4 - 20.4 g/L). Dilution factor: 0%, 20%, 40%, 60%, 80% and 100% of the stock solution. Behavioral observations were not recorded. Increased alkalinity values were due to a reaction between the titrant and toxicant. /Saccharin, sodium salt hydrate/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 23(SRC), determined from a log Kow of 0.91(2) and a regression-derived equation(3), indicates that saccharin is expected to have very mobility in soil(SRC). Volatilization of saccharin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.2X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(4). The pKa of saccharin is 1.31(5), indicating that this compound will partially exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(6). Saccharin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.0X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(7). Incubation experiments with activated sludge resulted in a first order half-life of 90 minutes with 78% removal efficiency after 3 hours(8) suggesting that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 23(SRC), determined from a log Kow of 0.91(2) and a regression-derived equation(3), indicates that saccharin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 1.2X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of three(SRC), from its log Kow(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC).Incubation experiments with activated sludge resulted in a first order half-life of 90 minutes with 78% removal efficiency after 3 hours(7) suggesting that biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), saccharin, which has an estimated vapor pressure of 1.0X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase saccharin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 22 hours(SRC), calculated from its rate constant of 5.9X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase saccharin may be removed from the air by wet or dry deposition(SRC). Saccharin contains chromophores that absorb at wavelengths >290 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

The Koc of saccharin is estimated as 20(SRC), using a log Kow of 0.91(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that saccharin is expected to have very high mobility in soil. The pKa of saccharin is 1.31(4), indicating that this compound will partially exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

/HUMAN EXPOSURE STUDIES/ Randomised, double-blind, placebo-controlled N-of-1 trial with a cross-over design /was conducted in order/ to determine whether there was a connection between the complaint of restless legs and the ingestion of artificial sweeteners in a patient with these symptoms after drinking certain 'light' beverages. During a period of 48 days, the patient took 4 capsules per day containing either 150 mg of cyclamate, 22.5 mg of saccharine, both sweeteners, or placebo on two successive days. Between each of these 2-day periods there was a 2-day rest period during which no capsules were taken. The hospital pharmacist had prepared the capsules and determined the sequence of the 2-day periods on a random basis. The patient did not know which capsules he was taking. Every day on arising, starting 3 weeks before the trial period, the patient noted the intensity and duration of the symptoms in the late evening and previous night. For this notation he used an 11-point scale, from 0 (= no restless legs) to 10 (= almost total inability to sleep because of restless legs). A score of 1-3 corresponded to mild symptoms that had no effect on the patient's sleep; at a score of 4-6 his sleep was disturbed and at a score of 7-10 the patient hardly slept at all. The patient had symptoms more often while using saccharine or the combination of saccharine and cyclamate than when taking the placebo (4 and 4 versus 2 of the 6 nights); moreover, the average score was then statistically significantly higher (5.2 and 5.8 versus 3.3). There was a connection between the patient's complaints of restless legs and the use of saccharine, but not the use of cyclamate.

/CASE REPORTS/ Idiosyncratic effects of saccharin on the liver were reported in a 70-year-old woman. Increased activities of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and alkaline phosphatase were found after oral administration of three pharmaceutical drugs of which saccharin was the only common constituent. The drugs were lorazepam, dihydroergocristine and chlordemethyldiazepam. Exposure to saccharin alone reproduced the effects.

/CASE REPORTS/ ...reported 5 patients in whom oral administration of 0.1 g saccharin caused pruritis and edematous papules on the trunk and limbs.

/EPIDEMIOLOGY STUDIES/ A SURVEY OF BLADDER CANCER PATIENTS & CONTROLS WITHOUT BLADDER CANCER SHOWED THAT IN GENERAL BLADDER CANCER RISK WAS NOT INCREASED BY NONNUTRITIVE SWEETENER SACCHARIN & CYCLAMATE USE. ADJUSTING FOR SMOKING HABITS, OCCUPATION, AGE, RACE, SEX, DIABETES MELLITUS, ETC DID NOT LEAD TO SIGNIFICANT CORRELATIONS BETWEEN THE SWEETENER USE & BLADDER CANCER.

For more Human Toxicity Excerpts (Complete) data for SACCHARIN (11 total), please visit the HSDB record page.

AEROBIC: The importance of biodegradation of saccharin in soil and water is unknown, but amides are usually susceptible to microbial metabolism(1). Saccharin was eliminated in wastewater treatment plants with activated sludge processes sampled in Zurich Switzerland; a mean removal efficiency of 90% was observed. Incubation experiments with activated sludge resulted in a first order half-life of 90 minutes with 78% removal efficiency after 3 hours. No loss was observed using sterile controls(2).

Saccharin and its salts

Group 3: Not classifiable as to its carcinogenicity to humans

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

1999

1998

NB Overall evaluation downgraded to Group 3 with supporting evidence from other relevant data

An estimated BCF of three was calculated in fish for saccharin(SRC), using a log Kow of 0.91(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). Bioconcentration of the substance was tested as a breakdown product of 3-(allyloxy)-1,1-dioxo-1lambda(6),2-benzothiazole; results indicated low bioconcentration potential(4).

The food additives saccharin, ammonium saccharin, calcium saccharin, and sodium saccharin may be safely used as sweetening agents in food in accordance with the following conditions /in part 180, section 37/, if the substitution for nutritive sweeteners is for a valid special dietary purpose and is in accord with current special dietary food regulations and policies or if the use or intended use is for an authorized technological purpose other than calorie reduction.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Saccharin is included in weight control drugs.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date 9/29/2006; Reporting date: 11/28/2006.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide is included on this list. Effective date: 9/29/2006; Sunset date: 11/28/2006.

...it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. ... /This study/ addressed the question of whether /they/ could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the ... aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca(2+) imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons,... /it was found/ that in both systems, .../sweeteners/ activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. ... /it was/also found that TRPV1 receptors were activated by CuSO(4), ZnSO(4), and FeSO(4), three salts known to produce a metallic taste sensation. In summary, .../the/ results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.

In three adult men given an intravenous bolus of 10 mg/kg bw sodium saccharin, the plasma concentration-time curve fitted a two-compartment open model with a terminal half-life of 70 min. /Sodium saccharin/

Six women with an average oral daily intake of 100-300 mg saccharin (form not specified) had maximum plasma concentrations after 0.5-1 hr and an elimination half-life of 7.5 hr.

... 3-(14)C-SACCHARIN WAS EXCRETED UNCHANGED, MAINLY IN THE URINE (85-92% IN 24 HR) BY ADULT HUMAN SUBJECTS, BOTH BEFORE & AFTER TAKING 1 G OF SACCHARIN DAILY FOR 21 DAYS; NO METABOLITE OF SACCHARIN WAS FOUND. THESE RESULTS WERE AMPLY CONFIRMED IN ANIMAL EXPERIMENTS, IN WHICH ORALLY ADMIN (14)C-SACCHARIN WAS EXCRETED ENTIRELY UNCHANGED BY RATS ON A NORMAL DIET & BY RATS ON A DIET CONTAINING 1% & 5% OF SACCHARIN FOR UP TO 12 MO. 80-90% OF THE DOSE WAS EXCRETED IN THE URINE, 10-20% IN THE FECES; NO (14)CO2 WAS FOUND IN THE EXHALED AIR, & NO (14)CO3(2-) OR 2-SULFAMOYLBENZOIC ACID IN THE URINE.

YIELDS IN MONKEYS SULFAMOYLBENZOIC ACID & O-SULFOBENZOIC ACID. /FROM TABLE/

EXPOSURE OF MALE CHARLES RIVER CDI RATS TO 5% SACCHARIN DIET IN UTERO & THROUGHOUT WEANING, DID NOT INDUCE DETECTABLE METABOLISM. NO METABOLITES WERE DETECTED IN URINE OF NORMAL RATS GIVEN TRACER DOSE. PRETREATMENT WITH 3-METHYLCHOLANTHRENE DID NOT INDUCE SACCHARIN METABOLISM.

One female and two male volunteers excreted 85-92% of a dose of 1g (3-14)C- saccharin unchanged in the urine within 24 hr, before or after taking 1 g saccharin daily for 21 days; no metabolites were found.

Within 48 h, 92% of a dose of 500 mg [14C]saccharin taken by six male volunteers was excreted in the urine and 5.8% in the faeces. Analysis of urine and feces by highperformance liquid chromatography and thin-layer chromatography revealed only unmetabolized saccharin.

TRANSPLACENTAL TRANSFER OF ... (14)C-SACCHARIN ADMIN BY IV INFUSION TO RHESUS MONKEYS IN LATE PREGNANCY, WAS RAPID, BUT SLIGHT. (14)C WAS CLEARED MORE SLOWLY FROM FETAL THAN FROM MATERNAL BLOOD, & WAS DISTRIBUTED IN ALL FETAL TISSUES EXAMINED ... WAS ONLY BIOTRANSFORMED TO LIMITED EXTENT & WAS RAPIDLY EXCRETED ... .

Three groups of five men were given sodium saccharin in single oral doses of 50, 150 or 333 mg/60 kg bw. Peak plasma concentrations occurred between 30 and 60 min after dosing, and 60 and 76% was excreted unchanged in urine at 6 and 24 h, respectively. /Sodium saccharin/

IN 3 VOLUNTEERS, 85-92% OF DOSES OF 1 G 3(14)C-SACCHARIN ADMIN ORALLY FOR 21 DAYS WAS EXCRETED UNCHANGED IN THE URINE WITHIN 24 HR; NO METABOLITES WERE FOUND. WITHIN 48 HR, 92.3% OF A DOSE OF 500 MG (14)C-SACCHARIN WAS EXCRETED IN THE URINE & 5.8% IN THE FECES.

After administration of 1-g doses of soluble (sodium) saccharin [form not specified] to three men, saccharin was excreted in the urine quantitatively unchanged by two of the subjects within 48 hr. In a subsequent experiment involving six subjects, none excreted the dose quantitatively within 72 hr, but no metabolism of saccharin was detected. /Sodium saccharin/

For more Absorption, Distribution and Excretion (Complete) data for SACCHARIN (13 total), please visit the HSDB record page.

Used as a non-nutritive sweetener, pharmaceutic aid (flavor), and in electroplating-bath brighteners; [Merck Index] Used as a cattle feed additive and in tobacco processing; [HSDB] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]

Electroplating [Category: Plate]

Non-nutritive sweetener; pharmaceutic aid (flavor). In formulations for electroplating-bath brighteners

A sweetening agent in Aromatic Cascara Sagrada Fluid extract and highly alcoholic preparations. ... It is used as a sweetening agent in vehicles, canned foods, and beverages and in diets for diabetics to replace sucrose.

Add sweetness with or without the extra calories ... /in/ beverages, baked goods, confections, table-top sugar, substitutes, many processed foods

NON-CALORIC SYNTHETIC SWEETENER IN TABLETS, LIQ PRODUCTS, SOFT DRINKS, DIETETIC FOODS, MISC PHARMACEUTICALS, CHEWING GUM, TOOTH PASTE, SMOKELESS TOBACCO PRODUCTS; ELECTROPLATING BATH ADDITIVE; CATTLE FEED ADDITIVE; ANTISEPTIC (FORMER USE); PRESERVATIVE TO RETARD FERMENTATION OF FOOD (FORMER USE).

o- & p-Toluenesulfonamide; 1,2-benzisothiazol-1,1-dioxide; 1,2-benzisothiazoline-1,1-dioxide; 3-aminobenzisothazol-1,1-dioxide; 5- & 6-chlorosaccharin; ammonium saccharin; methyl saccharin; diphenyl sulfone; ditolylsulphone isomers; o- & p-sulfamoylbenzoic acid; o-chlorobenzoic acid; o-sulfobenzoic acid (& ammonium salt); n-tetracosane; bis(4-carboxyphenyl)sulfone; toluene-2,4-disulfonamide; saccharin-o-toluenesulfonamide; saccharin-6-sulfonamide; N-methyl-o-toluene-sulfonamide; methyl-o-chlorobenzoate; 4,4'-dibenzoylsulfone; 2- or 3-carboxy thiaxanthone-5-dioxide; o-sulfobenzamide; methyl-o-sulfamoylbenzoate; methyl-N-methylsulfamoylbenzoate; saccharin-o-toluenesulfoxylimide; & other /Reported impurities in saccharin & sodium saccharin/

(1977) 1.35X10+9 G

(1982) 1.34X10+9 G

(1985) 8.07X10+8 g.

2023: 2,740,100 lb

(1977) AT LEAST 2.18X10+9 G (EST-INCL SALT)

(1985) Not reported

1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#1947]

For more U.S. Production (Complete) data for SACCHARIN (6 total), please visit the HSDB record page.

Global consumption (1000 tons): 37

The USA consumption pattern for saccharin (all forms) in 1976 has been estimated as follows: 77% in food uses: 45% in soft drinks, 18% in 'tabletop' sweetener, and 14% in other foods such as fruits, premixes, juices, sweets, chewing gum and jellies; and 23% in nonfood items: 10% in cosmetics such as toothpaste, mouthwash and lipstick, 7% in pharmaceuticals such as coatings on pills, 2% in smokeless tobacco products such as chewing tobacco and snuff, 2% in electroplating, 1% in cattle feed and 1% in miscellaneous uses. /Saccharin (all forms)/

In most countries, commercial saccharin is produced by the Remsen-Fahlberg process ... Toluene is used as the starting material and reacted with chlorosulfonic acid to a mixture of isomeric toluene sulfochlorides. In the presence of ammonia, 2-toluene sulfochloride forms 2-toluene sulfonic acid amide which is oxidized under appropriate conditions to saccharin. Potential oxidizing agents are potassium permanganate or chromic acid.

In the United States, the Maumee process is used. This starts from either anthranilic acid or its methyl ester, which can be obtained from phthalic acid anhydride. With sodium nitrite, anthranilic acid forms a diazonium compound, which is reacted with sulfur dioxide or sulfites, and chlorinated to 2-chlorosulfonylbenzoic acid methyl ester. In the presence of ammonia, this ester yields the respective amide, from which, after de-esterification, saccharin is obtained. Reaction with sodium hydroxide or calcium hydroxide forms the respective saccharin salts.

Saccharin is dissolved in an equimolar quantity of aqueous sodium hydroxide, and the solution is concentrated to crystallization. /Saccharin sodium/

Saccharin is reacted with a semimolar quantity of calcium hydroxide in aqueous medium, and the resulting solution is concentrated to crystallization. /Saccharin calcium/

A mixture of toluenesulfonic acids is converted into the sodium salt then distilled with phosphorus trichloride and chlorine to obtain the o-toluene sulfonyl chloride which, by means of ammonia, is converted into o-toluenesulfamide. This is oxidized with permanganate, treated with acid, and saccharin crystallized out.

Grades: Commercial; CP /Chemically pure: A grade designation signifying a minimum of impurities, but not 100% pure/; USP /United States Pharmacopeia/; FCC /Food Chemicals Codex/.

Sodium saccharin FCC (Food Chemicals Codex) is available in the USA in four grades: spray-dried, containing 3.0% moisture; powder, containing 5.0-5.8% moisture; pelletized, containing 10.5-11.5% moisture; and granular, containing 14.0-15.0% moisture. Each of these grades meets or exceeds the following Food Chemicals Codex specifications: 98-101% active ingredient on an anhydrous basis, 3-15% water, 100 mg/kg toluenesulphonamides, 30 mg/kg selenium, 10 mg/kg heavy metals (as lead) and 3 mg/kg arsenic. /Sodium saccharin/

Trade Names: Assugrin vollsuss (also contains sodium cyclamate); Garantose; Glucid; Gluside; Hermesetas; Kandiset; Natreen (also contains sodium cyclamate); Sacarina; 550 Saccharin; Saccharina; Saccharinol; Saccharinose; Saccharol; Saxin; Sucre Edulcor; Sucrette; Sykose; Zaharina.

Available in the USA as saccharin insoluble powder FCC (Food Chemicals Codex): 98-101% active ingredient on an anhydrous basis, a maximum of 100 mg/kg toluenesulphonamides, 30 mg/kg selenium, 10 mg/kg heavy metals (as lead) & 3 mg/kg arsenic ... Available in the USA as a USP grade containing 98-101% active ingredient on an anhydrous basis.

Fragrance Ingredients

Food Additives -> SWEETENER -> JECFA Functional Classes

Environmental transformation -> Pesticide transformation products (metabolite, successor)

Cosmetics -> Masking; Oral care

1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide: ACTIVE

In 1977, the FDA proposed a ban on saccharin because of the discovery of bladder tumors in some male rats fed with high doses of saccharin. Because no other nonnutritive sweetener was available at that time, the proposed ban faced strong opposition. Legislation to stay the ban has been passed in the U.S. Congress periodically. In December, 1991, the FDA withdrew its proposed ban. All saccharin-containing packaged products were required to carry a warning label indicating that saccharin has been determined to cause cancer in laboratory animals. In 2001, the warning label requirement was lifted by the Congress. In 2003, saccharin was delisted from California Proposition 65 (the so-called carcinogen list).

Industrial grade sodium saccharin is reportedly used as a brightener in nickel-plating baths, as an antistatic agent in plastics and textiles, as a polymer modifier and accelerator in photosensitive dispersions, and as a light fastness aid in nylon dyes. /Sodium saccharin/

Compared with dilute sucrose solutions, the sweetness intensity of saccharin is about 550, whereas the values for its salts are about 450. At medium or elevated use levels, saccharin sweetness is accompanied by a metallic or bitter aftertaste. Several masking agents for this side-taste have been suggested, and sweetener blends, especially a blend of 1 part sodium saccharin to 9 - 10 parts sodium cyclamate, are often used.