SACCHARIN

US Previously Marketed

First marketed in 1921

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H5NO3S
Molecular Weight	183.1859
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc2c(c1)C(=NS2(=O)=O)O

InChI

InChIKey=CVHZOJJKTDOEJC-UHFFFAOYSA-N

InChI=1S/C7H5NO3S/c9-7-5-3-1-2-4-6(5)12(10,11)8-7/h1-4H,(H,8,9)

HIDE SMILES / InChI

Molecular Formula	C7H5NO3S
Molecular Weight	183.1859
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet
Curator's Comment:: description was created based on several sources, including http://www.diabetes.co.uk/sweeteners/saccharin.html http://www.ukfoodguide.net/e954.htm

Saccharin is the most established of the artificial sweeteners on the market, this mixture of dextrose and saccharin has been in use for over a century and is found in diet versions of soft drinks. It is 300-500 times sweeter than sugar and contains zero calories. In 1977, the FDA tried to ban its use after evidence showed it caused cancer in rats. Extensive lobbying by the diet food industry allowed products to stay on the shelves as long as they carried warnings about the cancer risks in animals. This warning was removed in 2001 when the Calorie Control Council insisted the link between animal and human cancers could not automatically be made. Consumption of saccharin-sweetened products can benefit diabetics as the substance goes directly through the human digestive system without being digested. While saccharin has no food energy, it can trigger the release of insulin in humans due to its sweet taste. The T1R2/R3 sweet taste receptor exist on the surface of pancreatic beta cells. Saccharin is a unique in that it inhibits glucose-stimulated insulin secretion (GSIS) at submaximal and maximal glucose concentrations, with the other sweeteners having no effect. Investigation of saccharin’s dose-response characteristics showed that concentrations of 0.1 and 0.5 mM stimulated insulin secretion, while concentrations of 1 and 2.5 mM inhibited insulin secretion. Saccharin’s effect on insulin secretion was shown to be reversible in INS-1 832/13 clonal pancreatic beta cells after chronic exposure to 1 mM saccharin. Artificial sweeteners may affect insulin secretion via interaction with the sweet taste receptor, also saccharin may affect other cellular processes linked to insulin secretion, and that these effects are both time- and concentration-dependent

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Taste receptor type 1 member 2 4 Target ID: Q8TE23 Gene ID: 80834.0 Gene Symbol: TAS1R2 Target Organism: Homo sapiens (Human) Sources: http://www.fasebj.org/content/25/1_Supplement/530.1	Binding Agent 413
Taste receptor type 1 member 3 9 Target ID: Q7RTX0 Gene ID: 83756.0 Gene Symbol: TAS1R3 Target Organism: Homo sapiens (Human) Sources: http://www.fasebj.org/content/25/1_Supplement/530.1	Binding Agent 413

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 924

C_max

Value	Dose	Co-administered	Analyte	Population
14 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
27 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
5800 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: PROBENECID	PROBENECID	SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3700 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
6500 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
6800 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7303723/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SACCHARIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B 9	CYP2B 7	CYP2B 18

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2B 22	inducer 772 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/	no		no (co-administration study) Comment: coadministration with bupropion: had no effect on the CYP2B activity Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/
CYP2B 22	inhibitor 1612 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/	no		no (co-administration study) Comment: coadministration with bupropion: saccharin had no inhibitory effect on CYP2B activity in vivo Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2B 7	substrate 1689 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266375/	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:32111	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:32111
ChemicalBook	CB1743735	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1743735
ChemicalBook	CB32485657	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32485657
MolPort	MolPort-000-881-701	https://www.molport.com/shop/molecule-link/MolPort-000-881-701
ZINC	ZINC000002560357	http://zinc15.docking.org/substances/ZINC000002560357
eMolecules	478184	https://www.emolecules.com/cgi-bin/more?vid=478184

PubMed

Title	Date	PubMed
Cytological and lectin histochemical characterization of secretion production and secretion composition in the tubular glands of the canine anal sacs.	2001	11173805
A new type of endo-xyloglucan transferase devoted to xyloglucan hydrolysis in the cell wall of azuki bean epicotyls.	2001 Feb	11230569
[Micelle-mediated extraction for concentrating conjugated bilirubin in urine].	2001 Feb	11218735
Na+-to-sugar stoichiometry of SGLT3.	2001 Feb	11208603
Involvement of PI 3-kinase in IGF-I stimulation of jejunal Na+-K+-ATPase activity and nutrient absorption.	2001 Feb	11208544
Diurnal rhythmicity in intestinal SGLT-1 function, V(max), and mRNA expression topography.	2001 Feb	11208542
Automated noninvasive measurement of cyclophosphamide-induced changes in murine voiding frequency and volume.	2001 Feb	11176453
Characterization of EDTA-soluble polysaccharides from the scape of Musa paradisiaca (banana).	2001 Feb	11171036
Role of GLUT1 gene in susceptibility to diabetic nephropathy in type 2 diabetes.	2001 Feb	11168944
Cysteine residues in the D-galactose-H+ symport protein of Escherichia coli: effects of mutagenesis on transport, reaction with N-ethylmaleimide and antibiotic binding.	2001 Feb 1	11171069
Glucans exhibit weak antioxidant activity, but stimulate macrophage free radical activity.	2001 Feb 15	11182295
Identification and characterization of neutral endopeptidase (EC 3. 4. 24. 11) from human prostasomes--localization in prostatic tissue and cell lines.	2001 Feb 15	11170145
Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver.	2001 Feb 8	11217863
Diabetes. Dialogue between muscle and fat.	2001 Feb 8	11217842
Further glucosides of lichens' acids from Central Asian lichens.	2001 Jan	11219812
An overview of pathophysiology and treatment of insulin resistance.	2001 Jan	11211569
GLUT4--at the cross roads between membrane trafficking and signal transduction.	2001 Jan	11208163
Distinct long-term regulation of glycerol and non-esterified fatty acid release by insulin and TNF-alpha in 3T3-L1 adipocytes.	2001 Jan	11206412
Distinct differences in binding capacity to saccharide epitopes in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, and glioblastomas.	2001 Jan	11202177
Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats.	2001 Jan	11198711
What's the truth about the health risks of sugar substitutes such as saccharin and aspartame?	2001 Jan	11198407
Hypoxia-Induced increase in FDG uptake in MCF7 cells.	2001 Jan	11197971
The Schistosoma mansoni host-interactive tegument forms from vesicle eruptions of a cyton network.	2001 Jan	11197766
The rate-limiting step for tumor [18F]fluoro-2-deoxy-D-glucose (FDG) incorporation.	2001 Jan	11182558
High-resolution genetic mapping of the saccharin preference locus (Sac) and the putative sweet taste receptor (T1R1) gene (Gpr70) to mouse distal Chromosome 4.	2001 Jan	11178737
Placental glucose transport in gestational diabetes mellitus.	2001 Jan	11174489
A saccharinate-iron(II) complex with a free saccharin molecule present, [Fe(phen)3]sac2.sacH.6H2O.	2001 Jan	11173377
Improved water solubility of neohesperidin dihydrochalcone in sweetener blends.	2001 Jan	11170576
Cellular responses of NG108-15 and SK-N-MC lines to sweet and bitter tastants as measured by extracellular acidification rates.	2001 Jan 1	11169615
Functional asymmetry of the sodium-D-glucose cotransporter expressed in yeast secretory vesicles.	2001 Jan 15	11220364
Polysaccharides of green Arabica and Robusta coffee beans.	2001 Jan 15	11217967
The occurrence of internal (1 --> 5)-linked arabinofuranose and arabinopyranose residues in arabinogalactan side chains from soybean pectic substances.	2001 Jan 15	11217953
Compositional analysis of glycosaminoglycans by electrospray mass spectrometry.	2001 Jan 15	11199971
Direct inhibition of the hexose transporter GLUT1 by tyrosine kinase inhibitors.	2001 Jan 23	11170395
Engineering conformational flexibility in the lactose permease of Escherichia coli: use of glycine-scanning mutagenesis to rescue mutant Glu325-->Asp.	2001 Jan 23	11170394
Identification of N- and O-linked oligosaccharides in human seminal vesicles.	2001 Jan-Feb	11191091
Effect of growth hormone on intestinal Na+/glucose cotransporter activity.	2001 Jan-Feb	11190985
Spatial compartmentalization of signal transduction in insulin action.	2001 Mar	11223878
Development of cataractous macrophthalmia in mice expressing an active MEK1 in the lens.	2001 Mar	11222509
Time-resolved study of the inner space of lactose permease.	2001 Mar	11222310
Effects of excitotoxic brain lesions on taste-mediated odor learning in the rat.	2001 Mar	11222055
Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract.	2001 Mar	11179432
Hormonal regulation of chicken intestinal NHE and SGLT-1 activities.	2001 Mar	11171642
Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats.	2001 Mar	11171610
Effects of cellular ATP depletion on glucose transport and insulin signaling in 3T3-L1 adipocytes.	2001 Mar	11171597
Glucose metabolism in perfused mouse hearts overexpressing human GLUT-4 glucose transporter.	2001 Mar	11171596
The CDTA-soluble pectic substances from soybean meal are composed of rhamnogalacturonan and xylogalacturonan but not homogalacturonan.	2001 Mar	11169388
Ceramide dissociates 3'-phosphoinositide production from pleckstrin homology domain translocation.	2001 Mar 1	11171115
GLUT4 vesicle trafficking in rat adipocytes after ethanol feeding: regulation by heterotrimeric G-proteins.	2001 Mar 1	11171110
Model of the 3-D structure of the GLUT3 glucose transporter and molecular dynamics simulation of glucose transport.	2001 Mar 1	11170207

Patents

Sample Use Guides

In Vivo Use Guide

no more than 80 to 3000 mg saccharin per kilogram or litre should be used

Route of Administration: Oral

In Vitro Use Guide

After assaying for prolactin (PRL) in saccharin-treated cultures, it was observed that this sweetener is also capable of stimulating PRL production two- to sixfold in a dose-dependent manner. Enhancement of PRL production can be observed at 0.5 mM saccharin, yet this is 10 times less than the saccharin concentration required to alter cell shape. These effects of saccharin on cell morphology and on PRL production are reversible in rat pituitary tumor cells (GH4C1). When added to cultures along with maximal concentrations of epidermal growth factor (EGF) or thyrotropin-releasing hormone (TRH), the effects of saccharin on PRL production are additive, suggesting that the actions of saccharin are mediated by a somewhat different pathway from that of the peptide hormones

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:18:22 UTC 2021` Edited by `admin` on `Fri Jun 25 21:18:22 UTC 2021`
Record UNII	FST467XS7D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SACCHARIN

Official Name

English

SACCHARIN [EP MONOGRAPH]

Common Name

English

SACCHARINUM [HPUS]

Common Name

English

SACCHARIN [INCI]

Common Name

English

INS-954(I)

Code

English

SACCHARIN [II]

Common Name

English

SACCHARIN [MI]

Common Name

English

SACCHARIN [JAN]

Common Name

English

SACCHARINUM

Common Name

English

E-954(I)

Code

English

1,2-BENZISOTHIAZOL-3(2H)-ONE, 1,1-DIOXIDE

Systematic Name

English

SACCHARIN [IARC]

Common Name

English

SACCHARIN [HSDB]

Common Name

English

SACCHARIN [FCC]

Common Name

English

1,2-BENZISOTHIAZOLIN-3-ONE 1,1-DIOXIDE

Systematic Name

English

SACCHARIN [MART.]

Common Name

English

NSC-5349

Code

English

SACCHARIN [USP-RS]

Common Name

English

SACCHARIN [WHO-DD]

Common Name

English

INS NO.954(I)

Code

English

SACCHARIN [VANDF]

Common Name

English

Classification Tree Code System Code

JECFA EVALUATION

INS-954(I)