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].

Absorption, Distribution and Excretion
After single intravenous doses of (14)C-trichlorogalactosucrose to dogs at a dose level of 2 mg/kg (5.8 uCi/kg) radioactivity was rapidly excreted mainly in the urine. Urinary excretion accounted for means of 29.3%, 63.9% and 74.1% of the dose during 3, 6 and 12 hours after dosing respectively, increasing to 80.9% of the dose after 5 days. Fecal excretion accounted for a mean of 10.4% dose after 24 hours, increasing to 11.9% dose after 5 days. Plasma radioactivity was maximal at 5 minutes after dosing (the first time of sampling, 8.46 ug equivalents/mL). Radioactivity in plasma declined in a multi-exponential fashion; concentrations decreased rapidly to a mean of 0.057 ug equivalents/ml at 12 hours after dosing but thereafter declined more slowly, and were still detectable in all animals at 120 hours after dosing (mean, 0.013 ug equivalents/ml). Consideration of whole-blood and plasma concentrations indicated that radioactivity was cleared more slowly from blood cells than from plasma.
(14)C-trichlorogalactosucrose (1 mg/kg; 100 uCi > 98% pure) was given orally dissolved in water to 8 normal, healthy male volunteers and blood, urine and feces collected for up to 5 days after the dose. The total recovery of (14)C-activity was 92.7% (range 87.8-99.2%) with most of the radioactivity 78.3% (range 69.4-89.6%) in the feces, and the remainder 14.4% (range 8.8-21.7%) in the urine. The plasma concentrations of (14)C-activity reached a peak at about 2 hr after the dose, with levels of (14)C equivalent to approximately 250 ng/mL of trichlorogalactosucrose. The plasma concentrations fell rapidly between 2 and 12 hr followed by a more gradual decrease until 72 hr by which time the levels of radioactivity were near or below the limit of accurate determination. The mean 'effective half-life' calculated on the basis of a mean residence time (MRT) of 18.8 hr gives a value of 13.0 hr.
Three male subjects given a single oral dose (1.11 mg/kg b.w., 0.3 uCi/kg) of trichlorogalactosucrose uniformly labelled with carbon-14 excreted an average of 13.5% of the radioactivity in urine and 82.1% in feces in 5 days. No (14)CO2 was detected in expired air collected during the initial 8 hours after dosing. Maximum levels of radioactivity in the blood occurred within 2-3 hours and in two of the subjects declined with a half-life of approximately 2.5 hours. Chromatographic examination of the 0-3 hours urines indicated the presence of only a single radioactive component.
After single oral doses of (14)C-trichlorogalactosucrose to non-pregnant and pregnant rabbits at a dose level of 10 mg/kg, radioactivity was excreted mainly in the feces. During 24 hours after dosing, a mean of 16.8% of the dose was excreted in the feces of non-pregnant animals, increasing to 31.8% during 48 hours and 54.7% during 120 hours. Excretion of radioactivity in the feces of pregnant rabbits was similar, with means of 27.8%, 43.0% and 65.2% of the dose excreted by this route during 24, 48 and 120 hours after dosing, respectively. Means of 5.3% and 4.2% dose were excreted in the feces of non-pregnant and pregnant rabbits respectively during 96-120 hours after dosing, indicating that excretion of radioactivity was not completed after 5 days, probably because of the coprophagic behavior of rabbits. During 24 hours, means of 8.3% and 8.6% of the dose were excreted in the urine of non-pregnant and pregnant rabbits, respectively. Mean totals of 22.3% (non-pregnant rabbits) and 21.5% (pregnant rabbits) of the dose was gradually excreted in the urine during 5 days after dosing. Radioactivity was still being excreted in the urine of rabbits (up to 2.9% dose) during 96-120 hours after dosing. Mean total recoveries of radioactivity from the urine and feces of non- pregnant and pregnant rabbits after 5 days accounted for 80.3% and 87.0% of the dose respectively. The dose not accounted for was presumably still to be excreted since a total of up to 8.4% of the dose was excreted during 96-120 hours after dosing. There were no notable differences in the absorption and excretion of single oral doses of (14)C-trichlorogalactosucrose between non-pregnant and pregnant rabbits.
For more Absorption, Distribution and Excretion (Complete) data for Sucralose (14 total), please visit the HSDB record page.

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Metabolism / Metabolites
Following a single oral dose of (14)C-sucralose (1mg/kg, 100 microCi) to eight male subjects, a mean of 14.5% (range 8.9 to 21.8%) of the radioactivity was excreted in urine and 78.3% (range 69.4 to 89.6%) in the feces, within 5 days. The total recovery of radioactivity averaged 92.8%. Plasma concentrations of radioactivity were maximal at about 2 hours after dosing. The mean residence time (MRT) for sucralose was 18.8 hr, while the effective half-life for the decline of plasma radioactivity was 13 hr. Two volunteers given a higher oral dose (10 mg/kg, 22.7 uCi) excreted a mean of 11.2% (9.6 and 12.7%) of the radioactivity in urine, and 85.5% (84.1 and 86.8%) in feces over 5 days. The total recovery of radioactivity was 96.7%. The radiolabelled material present in feces was essentially unchanged sucralose. Sucralose was the principal component in the urine together with two more polar components which accounted for only 2.6% of the administered dose (range 1.5 to 5.1% of dose); both metabolites possessed characteristics of glucuronide conjugates of sucralose.

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Biological Half-Life
Three male subjects given a single oral dose (1.11 mg/kg b.w., 0.3 uCi/kg) of trichlorogalactosucrose uniformly labelled with carbon-14 excreted an average of 13.5% of the radioactivity in urine and 82.1% in feces in 5 days. ... Maximum levels of radioactivity in the blood occurred within 2-3 hours and in two of the subjects declined with a half-life of approximately 2.5 hours.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Sucralose has been found in the breastmilk of some nursing mothers who report consuming artificially sweetened beverages and sweetener packets in the past 24 hours and in all women given a sucralose-sweetened drinks. Sucralose is poorly absorbed after oral ingestion and is not found in the plasma of most breastfed infants after maternal ingestion of sucralose. It is not likely to cause immediate adverse effects in breastfed infants or result in a sucralose intake greater than the acceptable daily intake. Ingestion of diet drinks containing low-calorie sweeteners might increase the risk of vomiting in breastfed infants. Some authors note that sucralose in milk might exceed the sweetness threshold in milk and affect intestinal enzymes and the microbiome. They suggest that women may wish to limit the consumption of nonnutritive sweeteners while breastfeeding because their effect on the nursing infants are unknown.
◉ Effects in Breastfed Infants
A cross-sectional survey assessed the dietary history of US mothers nursing infants between 11 and 15 weeks of age. The survey was used to estimate the amount of diet soda and fruit drinks consumed by the women. There were no statistically significant differences in infants’ weight or z-scores based on low calorie sweetener exposure. However, infants exposed to low calorie sweetener in milk once or less per week had a statistically significantly higher risk of vomiting than those who were not exposed. Greater exposure was not associated with vomiting. It was not possible to assess the effects of specific sweeteners.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Interactions
/The study/...investigated the ability of zinc sulfate (5, 25, 50 mM) to inhibit the sweetness of 12 chemically diverse sweeteners, which were all intensity matched to 300 mM sucrose [800 mM glucose, 475 mM fructose, 3.25 mM aspartame, 3.5 mM saccharin, 12 mM sodium cyclamate, 14 mM acesulfame-K, 1.04 M sorbitol, 0.629 mM sucralose, 0.375 mM neohesperidin dihydrochalcone (NHDC), 1.5 mM stevioside and 0.0163 mM thaumatin]. Zinc sulfate inhibited the sweetness of most compounds in a concentration dependent manner, peaking with 80% inhibition by 50 mM. Curiously, zinc sulfate never inhibited the sweetness of Na-cyclamate. This suggests that Na-cyclamate may access a sweet taste mechanism that is different from the other sweeteners, which were inhibited uniformly (except thaumatin) at every concentration of zinc sulfate.

[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 consisting of 4-chloro-4-deoxy-alpha-D-galactopyranose and 1,6-dichloro-1,6-dideoxy-beta-D-fructofuranose units linked by a glycosidic bond. It has a role as an environmental contaminant, a xenobiotic and a sweetening agent. It is a disaccharide derivative and an organochlorine compound.
Sucralose is an artificial sweetener used as a sugar substitute.
See also: Aspartame; saccharin; sodium cyclamate; sucralose (component of) ... View More ...

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Mechanism of Action
Positive allosteric modulators of the human sweet taste receptor ...developed as a new way of reducing dietary sugar intake .../can be used as/ ...valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, .../the study/ reveal how ...sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.

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.)