- Sucralose treatment induced accumulation of reactive oxygen species (ROS) in mesenchymal stromal cells. The cells were exposed to Sucralose at specified concentrations , and ROS levels were detected using relevant fluorescent probes. Additionally, Sucralose promoted adipogenesis in these cells, as evidenced by increased formation of lipid droplets and upregulated expression of adipogenic marker genes (detected by PCR and/or western blot). [2]

The incidence of all hematopoietic malignancies increases significantly in male mice exposed to sucralose at concentrations of 2,000 ppm (p≤0.01) and 16,000 ppm (p≤0.01), according to the results, and this connection is dose-related (p≤0.01). Under a microscope, it was discovered that leukemia was the primary cause of the majority of tumors in male mice given 2,000–16,000 ppm sucralose. These tumors affected the lungs, liver, spleen, lymph nodes, and bone marrow, and they were accompanied by widespread infiltration of surrounding tissues and diffuse infiltration of blood vessels [1].

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- Sucralose was administered to male Swiss mice via feed, starting from the prenatal period and continuing throughout their lifespan. The treatment resulted in a significant increase in the incidence of hematopoietic neoplasias in male mice compared to the control group. No significant effect on hematopoietic neoplasias was observed in female mice . [1]

- For mesenchymal stromal cell experiments: Cells were cultured in appropriate medium under standard conditions (37°C, 5% CO₂) until reaching logarithmic growth phase. Cells were then treated with Sucralose at different concentrations and incubated for a specified duration. To detect ROS, treated cells were stained with a ROS-specific fluorescent dye, washed, and analyzed using flow cytometry or fluorescence microscopy. For adipogenesis assessment, treated cells were cultured in adipogenic induction medium for an additional period; lipid droplets were stained with oil red O, and adipogenic marker gene expression was measured via PCR or western blot. [2]

- Animal model: Male and female Swiss mice (specific age/weight at study initiation to be confirmed by full text) were used, with samples derived from timed-pregnant females. Sucralose was administered via incorporation into the basal diet at three different dose levels (low, medium, high; specific doses to be confirmed by full text), plus a control group fed with the basal diet without Sucralose. Administration started from the prenatal period (when pregnant females were exposed to the Sucralose-containing diet) and continued throughout the lifespan of the offspring. Mice were monitored daily for general health status, body weight changes, and mortality. At the end of the study (or when mice reached natural death), necropsy was performed, and tissues (including hematopoietic organs such as bone marrow and spleen) were collected for pathological examination to detect hematopoietic neoplasias. [1]

Absorption, Distribution and Excretion
Following a single intravenous injection of 2 mg/kg (5.8 uCi/kg) of (14)C-trichlorogalactose sucrose into dogs, the radioactive material was rapidly excreted primarily through urine. At 3, 6, and 12 hours post-administration, urinary excretion accounted for 29.3%, 63.9%, and 74.1% of the administered dose, respectively, increasing to 80.9% after 5 days. At 24 hours post-administration, fecal excretion averaged 10.4% of the administered dose, increasing to 11.9% after 5 days. Plasma radioactivity peaked 5 minutes post-administration (8.46 μg equivalent/mL at initial sampling). Plasma radioactivity exhibited a multi-exponential decay; at 12 hours post-administration, the radioactivity concentration rapidly decreased to an average of 0.057 μg equivalent/mL, after which the rate of decline slowed, and radioactivity remained detectable in all animals at 120 hours post-administration (average 0.013 μg equivalent/mL). Whole blood and plasma concentration analyses showed that the clearance rate of radioactive material from blood cells was slower than that from plasma. (14)C-trichlorogalactosylsucrose (1 mg/kg; 100 μCurie, purity >98%) was dissolved in water and administered orally to eight healthy male volunteers. Blood, urine, and stool samples were collected within 5 days of administration. The total recovery rate of (14)C was 92.7% (range 87.8–99.2%), with the majority of the radioactive material (78.3%, range 69.4–89.6%) present in the stool and the remaining 14.4% (range 8.8–21.7%) in the urine. The plasma concentration of (14)C peaked approximately 2 hours after administration, equivalent to approximately 250 ng/mL of trichlorogalactosylsucrose. Plasma concentrations decreased rapidly over 2–12 hours, then gradually decreased until 72 hours, at which point the radioactivity level was close to or below the accurate determination limit. The mean effective half-life, calculated based on a mean residence time (MRT) of 18.8 hours, was 13.0 hours. Three male subjects received a single oral dose of 1.11 mg/kg body weight (0.3 μCi/kg) of uniformly carbon-14 labeled sucrose trichlorogalactose. Within 5 days, an average of 13.5% of the radioactive material was excreted in urine and 82.1% in feces. (14)CO2 was not detected in exhaled breath collected within the first 8 hours after administration. Peak levels of radioactive material in the blood occurred within 2–3 hours, with two subjects showing a decrease in radioactive material levels over a half-life of approximately 2.5 hours. Chromatographic analysis of urine from 0–3 hours showed the presence of only one radioactive component. In non-pregnant and pregnant rabbits, a single oral dose of 10 mg/kg of ¹⁴C-trichlorogalactose sucrose resulted in the primary excretion of radioactive material via feces. Within 24 hours of administration, an average of 16.8% of the dose was excreted in the feces of non-pregnant rabbits, increasing to 31.8% after 48 hours and 54.7% after 120 hours. The excretion of radioactive material in the feces of pregnant rabbits was similar, with average excretion rates of 27.8%, 43.0%, and 65.2% at 24, 48, and 120 hours, respectively. Within 96–120 hours of administration, averages of 5.3% and 4.2% of the dose were excreted in the feces of non-pregnant and pregnant rabbits, respectively, indicating that excretion of the radioactive material was not yet complete after 5 days, possibly due to coprophagia in the rabbits. Within 24 hours, averages of 8.3% and 8.6% of the dose were excreted in the urine of non-pregnant and pregnant rabbits, respectively. Within 5 days of administration, averages of 22.3% (non-pregnant rabbits) and 21.5% (pregnant rabbits) of the dose were gradually excreted in the urine. Within 96–120 hours of administration, radioactive material was still being excreted in the urine of rabbits (up to a maximum of 2.9%). Five days later, the mean total recovery of radioactive material in urine and feces of non-pregnant and pregnant rabbits was 80.3% and 87.0% of the administered dose, respectively. The remaining unrecovered dose may still need to be excreted, as 8.4% of the total dose was excreted within 96–120 hours after administration. There was no significant difference in absorption and excretion between non-pregnant and pregnant rabbits following a single oral administration of (14)C-galactosylsucrose. For more complete data on the absorption, distribution, and excretion of sucralose (14 in total), please visit the HSDB records page. Metabolites/Metabolites Following a single oral administration of (14)C-galactosylsucrose (1 mg/kg, 100 μCi) to eight male subjects, an average of 14.5% (range 8.9% to 21.8%) of the radioactive material was excreted in urine and 78.3% (range 69.4% to 89.6%) in feces within 5 days. The overall recovery rate of radioactive material was 92.8% on average. Peak plasma radioactivity was reached approximately 2 hours after administration. The mean residence time (MRT) of sucralose was 18.8 hours, and the effective half-life of plasma radioactivity decay was 13 hours. In two volunteers who received a higher oral dose (10 mg/kg, 22.7 μCi), an average of 11.2% (9.6% and 12.7%, respectively) of radioactivity was excreted in urine and 85.5% (84.1% and 86.8%, respectively) of radioactivity was excreted in feces over 5 days. The overall recovery rate of radioactivity was 96.7%. The radiolabeled material present in feces was essentially unchanged sucralose. The main component in urine was sucralose, with two other more polar components comprising only 2.6% of the administered dose (range 1.5% to 5.1%). Both metabolites were characteristic of sucralose glucuronide conjugates.

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Biological Half-Life
Three male subjects received a single oral dose of 1.11 mg/kg body weight (0.3 μCi/kg) of uniformly carbon-14 labeled trichlorogalactose sucrose. Over 5 days, an average of 13.5% of the radioactive material was excreted in the urine and 82.1% in the feces. …The peak of radioactivity in the blood occurred within 2–3 hours. In two subjects, the radioactivity levels decreased, with a half-life of approximately 2.5 hours.

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Sucralose was detected in the breast milk of lactating mothers who consumed artificially sweetened beverages and sweetener packets within the past 24 hours, as well as in all women who consumed beverages containing sucralose. The absorption rate of sucralose after oral administration is very low, and sucralose is undetectable in the plasma of most breastfed infants after maternal ingestion. Therefore, it is unlikely to cause immediate adverse effects on breastfed infants or lead to sucralose intake exceeding the acceptable daily intake. Consuming sugar-free beverages containing low-calorie sweeteners may increase the risk of vomiting in breastfed infants. Some authors have noted that the sucralose content in milk may exceed the sweetness threshold of milk and affect gut enzymes and the microbiota. They recommend that lactating women limit their intake of non-nutritive sweeteners, as their effects on breastfed infants are unclear.
◉ Effects on Breastfed Infants
A cross-sectional study assessed the dietary history of US mothers between 11 and 15 weeks after their infants' birth. The study was used to estimate the amount of sugar-free soft drinks and fruit juices consumed by these mothers. Results showed no statistically significant difference between infant weight or z-score and the intake of low-calorie sweeteners. However, infants who consumed low-calorie sweeteners once a week or less had a significantly higher risk of vomiting than infants who did not consume such sweeteners. Increased intake 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/This study/...investigated the ability of zinc sulfate (5, 25, 50 mM) to inhibit the sweetness of 12 chemically distinct sweeteners, all of which had an intensity matching that of 300 mM sucrose [800 mM glucose, 475 mM fructose, 3.25 mM aspartame, 3.5 mM saccharin, 12 mM sodium cyclohexylsulfamate, 14 mM acesulfame potassium, 1.04 M sorbitol, 0.629 mM sucralose, 0.375 mM neohesperidin dihydrochalcone (NHDC), 1.5 mM steviol glycoside, and 0.0163 mM sweet protein]. Zinc sulfate inhibited the sweetness of most compounds in a concentration-dependent manner, reaching a peak inhibition rate of 80% at 50 mM. Interestingly, zinc sulfate never inhibited the sweetness of sodium cyclohexylsulfamate. This suggests that sodium cyclohexylsulfamate may act on a sweetness mechanism different from other sweeteners, which are consistently inhibited at all zinc sulfate concentrations.

[1]. Sucralose administered in feed, beginning prenatally through lifespan, induces hematopoietic neoplasias in male swiss mice. Int J Occup Environ Health. 2016 Jan;22(1):7-17.

[2]. Sucralose promotes accumulation of reactive oxygen species (ROS) and adipogenesis in mesenchymal stromal cells. Stem Cell Res Ther. 2020 Jun 26;11(1):250.

Sucralose is a disaccharide derivative composed of 4-chloro-4-deoxy-α-D-galactopyranose and 1,6-dichloro-1,6-dideoxy-β-D-fructofuranose units linked by glycosidic bonds. It is both an environmental pollutant and an exogenous substance and sweetener. It is a disaccharide derivative and also an organochlorine compound. Sucralose is an artificial sweetener used as a sugar substitute. See also: aspartame; saccharin; sodium cyclohexylsulfamate; sucralose (ingredient)... See more...

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Mechanism of Action A positive allosteric modulator of human sweet taste receptors...developed as a novel approach to reducing dietary sugar intake.../can be used/...a valuable tool molecule for studying the general mechanism of positive allosteric regulation of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, this study reveals how sweetness enhancers follow mechanisms similar to those of natural umami enhancer molecules. Sweeteners bind to the hinge region of T1R2, inducing closure of its Venus flytrap domain; while enhancers bind near the opening, further stabilizing the closed active conformation of the receptor.

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- This study in male Swiss mice[1] focused on the long-term (lifetime) toxicological effects of sucralose, with particular attention to prenatal exposure, aiming to assess the potential carcinogenic risk of sucralose to the hematopoietic system. [1]
- In mesenchymal stromal cells[2], sucralose promotes adipogenesis and is thought to be related to the accumulation of reactive oxygen species (ROS), as ROS are key signaling molecules involved in the regulation of adipogenesis differentiation (the specific signaling pathway needs to be confirmed in full). [2]

C12H19CL3O8

397.6335

396.014

56038-13-2

Sucralose-d6;1459161-55-7

71485

White to off-white solid powder

1.7±0.1 g/cm3

669.4±55.0 °C at 760 mmHg

125.5ºC

358.7±31.5 °C

0.0±4.6 mmHg at 25°C

1.604

0.68

5

8

5

23

405

9

C([C@@H]1[C@@H]([C@@H]([C@H]([C@H](O1)O[C@]2([C@H]([C@@H]([C@H](O2)CCl)O)O)CCl)O)O)Cl)O

BAQAVOSOZGMPRM-QBMZZYIRSA-N

InChI=1S/C12H19Cl3O8/c13-1-4-7(17)10(20)12(3-14,22-4)23-11-9(19)8(18)6(15)5(2-16)21-11/h4-11,16-20H,1-3H2/t4-,5-,6+,7-,8+,9-,10+,11-,12+/m1/s1

(2R,3R,4R,5R,6R)-2-[(2R,3S,4S,5S)-2,5-bis(chloromethyl)-3,4-dihydroxyoxolan-2-yl]oxy-5-chloro-6-(hydroxymethyl)oxane-3,4-diol

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)

H2O : ~100 mg/mL (~251.49 mM)
DMSO : ~100 mg/mL (~251.49 mM)

Solubility in Formulation 1: 50 mg/mL (125.75 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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