Absorption, Distribution and Excretion
In late pregnancy, transplacental transfer of (14)C-saccharin to rhesus monkeys via intravenous infusion was rapid but mild. (14)C was cleared from fetal blood at a slower rate than from maternal blood and distributed in all fetal tissues examined… its biotransformation was limited and it was rapidly excreted… Five males in each of the three groups were given single oral doses of 50, 150, or 333 mg/60 kg body weight of sodium saccharin. Peak plasma concentrations were reached 30 to 60 minutes after administration, with 60% and 76% of the drug excreted unchanged in the urine within 6 and 24 hours, respectively. /Sodium Saccharin/ Three volunteers were given 1 gram of 3(14)C-saccharin orally for 21 consecutive days; 85-92% of the dose was excreted unchanged in the urine within 24 hours; no metabolites were found. Within 48 hours, 92.3% of a 500 mg (14)C-saccharin dose was excreted in urine and 5.8% in feces. Two of the three male subjects who ingested 1 gram of soluble (sodium) saccharin (unspecified form) excreted saccharin unchanged in their urine within 48 hours. In a subsequent study involving six subjects, none of the subjects excreted saccharin unchanged within 72 hours, but no saccharin metabolism was detected. /Sodium Saccharin/ For more complete data on the absorption, distribution, and excretion of saccharin (13 types), please visit the HSDB records page.

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Metabolism/Metabolites
…… 3-(14)C-saccharin was primarily excreted unchanged in urine (85-92% within 24 hours), observed in adults taking 1 gram of saccharin daily for 21 days; no saccharin metabolites were found. Animal studies fully confirmed these results. In the experiment, after oral administration of (14)C-saccharin, rats on a normal diet and rats fed diets containing 1% and 5% saccharin, respectively, completely excreted unchanged over a period of up to 12 months. 80-90% of the dose was excreted in urine and 10-20% in feces; (14)CO2 was not detected in exhaled breath, and (14)CO3(2-) or 2-sulfonylbenzoic acid was not detected in urine.
Production of sulfonylbenzoic acid and o-sulfonylbenzoic acid in monkeys. /Excerpt from Table/
Male Charles River CDI rats exposed to a 5% saccharin diet in utero and during weaning did not induce detectable metabolism. No metabolites were detected in the urine of normal rats given tracer doses. Pretreatment with 3-methylcholanthrene did not induce saccharin metabolism.
In one female and two male volunteers, 85-92% of 1 gram of (3-14)C-saccharin was excreted unchanged in urine within 24 hours. This dose was measured before or after a 21-day daily intake of 1 gram of saccharin; no metabolites were found.
In six male volunteers, 92% of the dose of 500 mg [14C]saccharin was excreted in urine and 5.8% in feces within 48 hours. Analysis of urine and feces by high-performance liquid chromatography and thin-layer chromatography showed that only unmetabolized saccharin was present.
Biological half-life
In three adult males, plasma concentration-time curves following intravenous injection of 10 mg/kg body weight of sodium saccharin conformed to a two-compartment open model, with a terminal half-life of 70 minutes. /Sodium Saccharin/
In six women, with an average daily oral intake of 100-300 mg of saccharin (dosage form not specified), peak plasma concentrations were reached after 0.5-1 hour, with an elimination half-life of 7.5 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Because breast milk has a low saccharin content, infants ingest very little after their mothers' normal intake, and it is not expected to have any adverse effects on breastfed infants, nor is it likely to reach the acceptable daily intake. Consuming sugar-free beverages containing low-calorie sweeteners may increase the risk of vomiting in breastfed infants. However, some authors suggest that women may need to limit their intake during breastfeeding because the effects of non-nutritive sweeteners on breastfed infants are not well understood. ◉ Effects on Breastfed Infants
A cross-sectional survey assessed the dietary history of US mothers between 11 and 15 weeks after their infants' birth. This survey was used to estimate the amount of sugar-free soft drinks and fruit juices consumed by these women. There were no statistically significant differences in infant weight or z-score based on exposure to low-calorie sweeteners. However, infants who consumed low-calorie sweeteners via milk once a week or less had a significantly higher risk of vomiting than infants who were not exposed to sweeteners. Higher exposure was not associated with vomiting. The effects of specific sweeteners could not be assessed.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Interactions
It is now well-established that the interaction of multiple environmental factors may increase the incidence of certain human cancers more significantly than exposure to a single carcinogen. Using an in vivo rat model, the synergistic effect of subcarcinogenic doses of the potent bladder carcinogen N-methyl-N-nitrosourea and saccharin in bladder cancer development was demonstrated.
Since both sodium L-ascorbate and sodium saccharin promote the two-stage development of bladder cancer in rats, the synergistic effect of these two chemicals was investigated, with particular attention paid to the effects of urine pH and sodium ion concentration. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks, followed by feeding them a basal diet containing 5% sodium saccharin, 5% sodium L-ascorbate, 5% sodium saccharin + 5% sodium L-ascorbate, 5% L-ascorbic acid, 5% sodium saccharin + 5% L-ascorbic acid, or no added chemicals for 32 weeks. Treatment with sodium saccharin or sodium L-ascorbate alone significantly increased the incidence of bladder tumors and precancerous lesions. Compared with the control group, the sodium saccharin + sodium L-ascorbate treatment group also significantly increased the incidence of bladder lesions, and the number of lesions was greater than the sum of the number of lesions in the sodium saccharin or sodium L-ascorbate treatment groups alone. Conversely, treatment with sodium saccharin plus sodium L-ascorbate induced bladder cancer and papillary tumors in rats, leading to increased urinary pH and sodium ion concentration, but the magnitude of the increase was not significantly different from that in rats fed sodium saccharin or sodium L-ascorbate alone. However, while sodium saccharin plus L-ascorbic acid increased urinary sodium ion concentration, it did not cause an increase in urinary pH. Therefore, the bladder cancer-promoting effect of sodium saccharin can be synergistically enhanced by sodium L-ascorbate and inhibited by L-ascorbic acid. This regulatory effect is related to changes in urinary pH and sodium ion concentration. A long-term feeding trial was conducted on rats using a 10:1 mixture of sodium cyclohexylsulfamate and saccharin. The experimental mixture was fed at dietary levels to 35 male and 45 female rats to achieve intakes of 500, 1120, and 2500 mg/kg. The only critically significant positive result was the development of papillary carcinoma in the bladder of 12 out of 70 rats fed the highest dietary dose mixture (equivalent to approximately 2500 mg/kg) over 78 to 105 cycles. N-Methyl-N-nitrosourea was used as a carcinogen and significantly increased the incidence of bladder cancer in saccharin-treated rats. Saccharin is a weak initiator of bladder cancer in rats but a potent promoter. For more complete data on interactions with saccharin (15 items in total), please visit the HSDB record page.

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Non-human toxicity values
Rat intraperitoneal LD50: 7100 mg/kg /sodium saccharin/
Rat oral LD50: 14200 mg/kg /sodium saccharin/
Mouse oral LD50: 17500 mg/kg /sodium saccharin/

Saccharin (industrial grade) is a white crystalline solid, odorless or slightly aromatic, with a sweet taste. (NTP, 1992)
Sodium saccharin is an odorless white crystalline solid or crystalline powder. Its aqueous solution is neutral or alkaline to litmus, but anoxic to phenolphthalein. It readily effloresces in dry air. It has a sweet taste. (NTP, 1992)
Saccharin is a 1,2-benzisothiazole compound with a ketone group at position 3 and two carbonyl substituents at position 1. It is used as an artificial sweetener. It is both a sweetener and an exogenous substance and environmental pollutant. It is a 1,2-benzisothiazole and N-sulfonylformamide.
Saccharin has been studied for the treatment of hypertension and hyperglycemia.
A flavoring agent and a non-nutritive sweetener. See also: aspartame; saccharin; sodium cyclohexylsulfamate; sucralose (ingredients)... See more...

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Mechanism of Action
... Studies have shown that activation of specific T2R bitter receptors is associated with the bitter aftertaste of saccharin and acesulfame potassium. ... This study investigated whether they could stimulate transient receptor potential vanillic acid receptor 1 (TRPV1), as these receptors can be activated by a variety of structurally different chemicals. Furthermore, TRPV1 receptors and/or their variants are present in taste receptor cells and nerve endings throughout the oral cavity. Therefore, activation of TRPV1 may be related to... aftertaste, and even possibly to the little-known metallic taste. Using Ca²⁺ imaging, in heterologous expression in human embryonic kidney (HEK) 293 cells and isolated primary sensory neurons, it was found that in both systems, ... sweeteners activated TRPV1 receptors and also enhanced the sensitivity of these channels to acid and heat. The study also found that three salts known to produce metallic tastes—copper sulfate (CuSO₄), zinc sulfate (ZnSO₄), and ferrous sulfate (FeSO₄)—can also activate TRPV1 receptors. In summary, the findings reveal a new class of compounds that can activate TRPV1, providing a molecular mechanism that can explain the off-flavors of sweeteners and the metallic taste of salts.

C7H5NO3S

205.16

204.98

128-44-9

Saccharin;81-07-2

5143

Monoclinic crystals
Needles from acetone; prisms from alcohol; leaflets from water
White, crystalline powder
White crystals

438.9ºC at 760 mmHg

>300°C

219.3ºC

1.77E-08mmHg at 25°C

1.082

1

3

0

12

303

0

S1(C2=C([H])C([H])=C([H])C([H])=C2C(N1[H])=O)(=O)=O

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)

1,1-dioxo-1,2-benzothiazol-3-one

CCRIS 706Saccharin, sodium Saccharin sodium

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)