High-intensity sweeteners have been suggested as potential organic contaminants due to their widespread use in food, drugs and sanitary products. As a consequence, they are introduced into the environment by different pathways, affecting aquatic life. In this study, a method based on solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) has been developed and validated for the determination of eight sweeteners (saccharin, cyclamate, aspartame, acesulfame, neohesperidin dihydrochalcone, sucralose, stevioside and glycyrrhizic acid) in river water and wastewater. To get the maximum recoveries in SPE, several commercial sorbents were tested and Oasis HLB gave the best results, with recoveries higher than 41% for all of the compounds in the different matrices. Method limits of detection were in the range of 0.001-0.04μg/L in river water and 0.01-0.5μg/L in influent and effluent wastewater. Method reproducibility between days (n=5) was below 15% for all compounds. The method was applied to the determination of sweeteners in various river waters and wastewaters in Catalonia. Cyclamate, aspartame, neohesperidin dihydrochalcone, acesulfame and sucralose were found in river water, with the two last compounds being present at the highest values (1.62μg/L for acesulfame and 3.57μg/L for sucralose). In influent and effluent wastewater, all of the compounds were found at concentration levels ranging from 0.05 to 155μg/L except for stevioside and neohesperidin dihydrochalcone, which were not detected (1).

Evaluating the environmental impact of artificial sweeteners: a study of their distributions, photodegradation and toxicities (2).

As for human health, Saccharin was (2014) tested in concentrations equal to those found in soft drinks, but, at least in this study, no interference was found on the aryl receptor and on the glucocorticoid receptor (3 ).

References_______________________________________________

(1) Determination of high-intensity sweeteners in river water and wastewater by solid-phase extraction and liquid chromatography-tandem mass spectrometry.

Arbeláez P, Borrull F, Pocurull E, Marcé RM.
J Chromatogr A. 2015 May

(2) Evaluating the environmental impact of artificial sweeteners: a study of their distributions, photodegradation and toxicities.
Sang Z, Jiang Y, Tsoi YK, Leung KS.
Water Res. 2014 Apr

(3) Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells.
Kamenickova A, Pecova M, Bachleda P, Dvorak Z.
Toxicol In Vitro. 2013 Dec.

Saccharin is a chemical compound, (1,2-benzisothiazol-3-one-1,1-dioxide).

The synthesis process takes place in different steps:

• Production of toluene. In the first step, toluene is obtained from crude oil through a refining process.
• Sulphonation. Toluene is reacted with sulphuric acid in a process known as sulphonation, which adds a sulphonic acid group to the toluene molecule.
• Oxidation. Toluene sulphonate is oxidised, usually with nitric acid, to produce a compound called methyl anthranilate.
• Conversion to saccharin. Methyl anthranilate is converted to saccharin through a series of reactions involving nitrous acid, sulphur dioxide, chlorine and ammonia.

It is in the form of a white crystalline powder with an intense sweet taste, odourless. Stable. Incompatible with strong oxidising agents. Soluble in acetone. Crystal sizes: 4-6, 5-8, 10-20, 20-40, 80-100 mesh.

What it is used for and where

Food and Pharmaceuticals

It is a non-caloric artificial sweetener widely used as a sugar substitute to control body weight or blood sugar, absorbed through intact intestinal epithelial cells and is not metabolised. 

Discovered in 1879 by researchers at Johns Hopkins University, it is low in calories. Its sweetening power is about 450 times that of sucrose.

Sodium saccharin, which is a salt of saccharin, is often found in pharmaceuticals and cosmetics and is used in the same way as saccharin as it is, from a practical point of view, the same component, albeit with a different formula and molecular weight.

Saccharin is used extensively by the food industry as a sweetener in baked goods, jams, canned fruit, candies, chewing gum.

It is also used in pharmaceuticals and by diabetics as a sugar substitute.

As with other sweeteners, the field of scientific research is teeming with studies on its food safety and the results are still mixed. Hundreds of clinical studies have tested saccharin in laboratory rats, monkeys and humans. In practice, some studies claim that impurities in commercial saccharin may have been responsible for tumours (1), whereas according to the current literature, the possible risk of artificial sweeteners to induce cancer appears to be negligible (2). Even relatively high levels of saccharin intake among diabetic subjects have not been found to increase the risk of cancer in general (3).

Cosmetics

Fragrance. It plays a decisive and important role in the formulation of cosmetic products as it provides the possibility of enhancing, masking or adding fragrance to the final product, increasing its marketability. It is able to create a perceptible pleasant odour, masking a bad smell. The consumer always expects to find a pleasant or distinctive scent in a cosmetic product. 

Oral care agent. This ingredient can be placed in the oral cavity to improve and/or maintain oral hygiene and health, to prevent or improve a disorder of the teeth, gums, mucous membrane. It provides cosmetic effects to the oral cavity as a protector, cleanser, deodorant.

Flavoring agent. The purpose of this ingredient is to modify the solution to impart a certain flavour. Natural flavouring extracts are rather expensive, so the cosmetic and pharmaceutical industries resort to synthesised substances that have sensory characteristics mostly similar to natural flavourings or are naturally equivalent. This ingredient is isolated through chemical processes or is synthesised from chemicals. It is also referred to as Aroma.

Other applications

Bleaching agent in the nickel industry, can improve lustre.

Safety

It is considered an environmental contaminant.

Saccharin studies

Typical commercial product characteristics Saccharin

• Molecular Formula  C₇H₅NO₃S
• Molecular Weight   183.181 g/mol
• Exact Mass    182.999008
• CAS   81-07-2
• EC Number   201-321-0  204-886-1
• UNII   FST467XS7D
• DSSTox Substance ID  DTXSID5021251    DTXSID5021253
• IUPAC  1,1-dioxo-1,2-benzothiazol-3-one
• InChI=1S/C7H5NO3S/c9-7-5-3-1-2-4-6(5)12(10,11)8-7/h1-4H,(H,8,9)  
• InChl Key      CVHZOJJKTDOEJC-UHFFFAOYSA-N
• SMILES    C1=CC=C2C(=C1)C(=O)NS2(=O)=O
• FEMA Number: 2997
• PubChem Substance ID 24854444
• MDL number MFCD00005866
• Beilstein Registry Number 6888
• ChEBI    32111
• RTECS    DE4200000
• UN    3077
• NSC    5349    757878
• RXCUI    9509

Synonyms

• o-Sulfobenzimide
• Saccharinose
• o-Benzoic sulfimide
• Garantose
• Saccharimide
• Saccharinol
• Saccharine
• Gluside
• Benzosulfimide
• Saccharin acid
• Benzoic sulfimide
• Benzosulfinide
• o-Benzosulfimide
• 1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide
• Benzosulphimide
• Anhydro-o-sulfaminebenzoic acid
• 3-Hydroxybenzisothiazole S,S-dioxide
• Benzo[d]isothiazol-3(2H)-one 1,1-dioxide
• 2,3-Dihydro-3-oxobenzisosulphonazole
• 2,3-Dihydro-3-oxobenzisosulfonazole
• 1,2-Dihydro-2-ketobenzisosulphonazole
• 2-Sulphobenzoic imide
• 3-Hydroxybenzisothiazole-S,S-dioxide
• Benzoic acid sulfimide
• Benzosulfimide, O-
• 1,2-Dihydro-2-ketobenzisosulfonazole
• 1,1-dioxo-1,2-benzothiazol-3-one
• 3-Benzisothiazolinone 1,1-dioxide
• 1,1-Dioxo-1,2-benzisothiazol-3(2H)-one
• 1,1-Dioxide-1,2-benzisothiazolin-3-one
• 1,2-Benzothiazol-3(2H)-one 1,1-dioxide
• 1,1-Dioxo-1,2-dihydro-benzo[d]isothiazol-3-one
• CHEBI:32111
• 1,1-Diox-1,2-benzisothiazol-3-one
• 2,3-Dihydro-1,2-benzoisothiazol-3-one-1,1-dioxide
• 2,3-Dihydroxy-1,2-benzisothiazol-3-one-1,1-dioxide
• o-Sulfonbenzoic acid imide sodium salt
• 2-hydrobenzo[d]isothiazole-1,1,3-trione
• Glycophenol
• 2-Sulfobenzoic imide
• Neosaccharin

References____________________________________________________________________

(1) Arnold DL. Two-generation saccharin bioassays. Environ Health Perspect. 1983 Apr;50:27-36. doi: 10.1289/ehp.835027. 

(2) Weihrauch MR, Diehl V. Artificial sweeteners--do they bear a carcinogenic risk? Ann Oncol. 2004 Oct;15(10):1460-5. doi: 10.1093/annonc/mdh256.

Lohner S, Toews I, Meerpohl JJ. Health outcomes of non-nutritive sweeteners: analysis of the research landscape. Nutr J. 2017 Sep 8;16(1):55. doi: 10.1186/s12937-017-0278-x.

(3) Armstrong B, Lea AJ, Adelstein AM, Donovan JW, White GC, Ruttle S. Cancer mortality and saccharin consumption in diabetics. Br J Prev Soc Med. 1976 Sep;30(3):151-7. doi: 10.1136/jech.30.3.151.