Sucralose

397.633

397.63

259-952-2

96K6UQ3ZD4

759272

DTXSID1040245

White to off white, crystalline powder|Anhydrous crystalline form: orthorhombic, needle-like crystals|Syrup

2932999099

128.84

-1.5

White crystal powder

1.375 g/cm

130 °C

104-107 C

358.7ºC

1.604

In water, 2.27X10+4 mg/L at 25 deg C (est)

Hygroscopic, -20ºC Freezer, Under Inert Atmosphere

3.25X10-14 mm Hg at 25 deg C (est)

LD50 orally in Rabbit: > 10000 mg/kg

Intensely sweet taste

Henry's Law constant = 3.99X10-19 atm-cu m/mol at 25 °C (est)

177.2 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|179.16 Ų [M-H]-

Sugar equivalence value relative to sucrose = 600|In water ... stable to heat over a wide range of pH|Hydroxyl radical reaction rate constant = 5.42X10-11 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

3

R36/37/38

S26; S37/39

LW5440140

Xi

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Sucralose is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.

SRP: In bulk storage or manufacturing situations where combustible dusts can collect in sufficient concentrations to give rise to an explosion/deflagration, reasonable precautions shall be taken to reduce or eliminate the hazard. Efforts shall be made to control or eliminate the five elements necessary to initiate a dust explosion. These include combustible dust (fuel), ignition source (heat), oxygen in air (oxidizer), and dispersion of dust particles in sufficient quantity and concentration as well as confinement of the dust cloud. General guidance in these efforts can be found in OSHA's "Combustible Dust in Industry; Preventing and Mitigating the Effects of Fire and Explosions", which list measures to control dusts, eliminate ignition sources, and limit the effects of explosions.

Sucralose concentrations in untreated and treated wastewater from the Canton of Zurich, Switzerland, collected in 2008(1). [Table#7901]

/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.

/AQUATIC SPECIES/ .../The report presents sucralose/ bioaccumulation studies in the freshwater alga Pseudokirchneriella subcapitata, the crustacean Daphnia magna, and zebrafish (Danio rerio). The freshwater algae and the daphnid tests were performed using a 48-hr static exposure system, whereas the zebrafish test was performed using a 48-hr semi static exposure system followed by 48 hr flow-through of clean water for the depuration phase. All three studies were conducted with two exposure concentrations (10 and 100 mg/L), and the concentrations of sucralose in water and biota were verified by liquid chromatography/mass spectrometry. The studies showed that uptake of sucralose was assumed to achieve a steady state within the first 48 hr, and the bioconcentration factor at the assumed steady state (BCF(SS) ) was calculated to be less than 1 for algae and between 1.6 to 2.2 for the daphnids. The fish BCF(SS), assumed to occur between 24 to 48 hours, were calculated to be less than 1 for both concentrations tested. A first-order one-compartment (uptake phase) and a first-order two-compartment (elimination phase) model characterized the uptake and depuration kinetics in zebrafish (k(1)=0.027-0.038/hr and k(2)=0.206-0.222/hr, t(95)=13.5 to 14.6 hr, t(50)=3.1 to 3.3 hr, and BCF(kinetic)=0.4 to 0.9). .../Therefore,/ sucralose does not bioaccumulate in aquatic organisms from different tiers of the food web, and ... the BCF's obtained were considerably lower than the criteria set to identify persistent, bioaccumulative, and toxic substances (i.e., BCF < 2,000).

Sucralose's production and use as a non-nutritive sweetener(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that sucralose is expected to have very high mobility in soil(SRC). Volatilization of sucralose from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.0X10-19 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Sucralose is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Mineralization of 14CO2-labeled sucralose ranged from 32.6 to 60.4% over 20 to 101 days using four loam soils(5), indicating that biodegradation may be an important environmental fate process in soil(SRC). However, in an anaerobic environment, sucralose was not mineralized in soil(5).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that sucralose is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.0X10-19 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of three(SRC), from an estimated log Kow of -1.00(6)and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Sucralose is not eliminated in wastewater treatment plants and was shown to be very persistent in surface waters(8), indicating that biodegradation is not an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sucralose, which has an estimated vapor pressure of 3.2X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase sucralose may be removed from the air by wet or dry deposition(SRC). Sucralose does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Sucralose is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Sucralose does not contain chromophores that absorb at wavelengths >290 nm(1), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of three was calculated in fish for sucralose(SRC), using an estimated log Kow of -1.00(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of sucralose can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that sucralose is expected to have very high mobility in soil.

The Henry's Law constant for sucralose is estimated as 4.0X10-19 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that sucralose is expected to be essentially nonvolatile from water and moist soil surfaces(2). Sucralose is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-14 mm Hg(SRC), determined from a fragment constant method(3).

GROUNDWATER: Sucralose was not detected in groundwater sampled in Zurich Switzerland, sampled between August and November 2008(1).|SURFACE WATER: A maxium sucralose concentration of 0.6 ug/L was reported in the River Glatt in Zurich, Switzerland, sampled between June and October 2008. It was not detected in eight area lakes(1).

Occupational exposure to sucralose may occur through dermal contact with this compound at workplaces where sucralose is produced or used. Monitoring and use data indicate that the general population may be exposed to sucralose via ingestion of contaminated water and consumer containing sucralose. (SRC)

Substances that sweeten food, beverages, medications, etc., such as sugar, saccharine or other low-calorie synthetic products. (From Random House Unabridged Dictionary, 2d ed) (See all compounds classified as Sweetening Agents.)

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.

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.

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.

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.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ A total of .../26/ patients with glycosylated hemoglobin levels < 10% completed ... double-blind cross-over study. After an overnight fast, patients were administered opaque capsules containing either 1,000 mg sucralose or cellulose placebo, followed by a standardized 360-kcal liquid breakfast. Plasma glucose and serum C-peptide levels were measured over the next 4 hr. Regardless of the type of diabetes, areas under the curves for changes of plasma glucose and serum C-peptide levels after sucralose administration were not significantly different from those after placebo. During test meals with sucralose, one episode of symptomatic hypoglycemia occurred in ... three patients, but these episodes were not considered the result of sucralose administration. The present results support the conclusion that sucralose consumption does not adversely affect short-term blood glucose control in patients with diabetes.|/HUMAN EXPOSURE STUDIES/ Eight ... subjects (4 male and 4 female) first received ascending oral doses of TGS in doses of 0.0, 1.0, 2.5, 5.0 and 10.0 mg/kg at 48-hour intervals. This was followed by 7 days continuous administration of 2.0 mg/kg daily for the first three days and 5.0 mg/kg daily for the remaining four days. There were no adverse reactions or complaints throughout the study. No clinically significant changes were observed in temperature, pulse, blood pressure (supine or standing), respiratory rate and general conditions. Detailed hematological and biochemical studies were made before the study, then after 2.0 mg/kg/day and 5.0 mg/kg/day during the second phase. There were no abnormalities in any of the parameters measured. Electrocardiogram studies throughout showed no changes from the initial findings. Urinary examination showed no abnormalities, and an assessment of 24 hour urine volumes throughout the study detected no effects. Blood insulin levels measured one half hour after each dosage showed levels ranging from 4.038.0 milliunits/mL, which were within the fasting range. On Day 25 of the study, blood insulin levels were measured one half hour after 50 g standard sucrose. All showed the characteristic increase within the range 53-108 milliunits/mL.|/CASE REPORTS/ /The study/ report a patient with attacks of migraine consistently triggered by sucralose. She also suffers from menstrually related migraine that had been well-controlled for several months since she switched her contraceptive from fixed estrogen to triphasic contraceptive pills. Some attacks triggered by sucralose were preceded by aura, and she had never experienced migraine with aura before. Withdrawal of the compound was associated with complete resolution of the attacks. Single-blind exposure (vs. sugar) triggered the attacks, after an attack-free period.

1',4',6'-trichloro-1',4,6'-trideoxygalactosucrose

Aqueous solutions

Chlorinated sucrose derivative with enhanced sweetness|Compared with dilute sucrose solution, sucralose is about 600 times sweeter. The sweetness is perceived with a slight delay and a lasting effect, similar to aspartame, and generally considered of good quality.|Solid sucralose is not fully stable, and slowly releases HCl, with discoloration. In contrast, aqueous solutions are highly stable, and it is marketed in this form.

Food additives|Food Additives -> SWEETENER; -> JECFA Functional Classes

Food Additives -> SWEETENER;