Lactitol

344.31

344.31

209-566-5

L2B0WJF7ZY

760415

DTXSID9044247

Crystals from absolute ethanol

A06AD12|A - Alimentary tract and metabolism

201

-5.53 (est)

Crystalline powder or colourless solution. Crystalline products occur in anhydrous, monohydrate and dihydrate forms. Nickel is used as a catalyst.

1.69±0.1 g/cm3(Predicted)

146 °C

788.5ºC at 760 mmHg

430.7ºC

1.634

In water, 57.2 g/100 g at 20 deg C. ... With increasing temperature the solubility rises considerably

When /lactitol/ is stored in a unopened container at 25 deg C and 60% relative humidity, a shelf-life in excess of 3 years is appropriate.

6.55X10-16 mm Hg at 25 deg C (est)

D23 +14° (c = 4 in water)

30-40% of that of sucrose. The taste is sweet and clean

Strongly hygroscopic|Heat of solution: 27.7 J/g|White, sweet, odorless, crystalline solid. Non-hygroscopic. MP: 94-97 °C, water of crystallization evaporates 145-185 °C; also reported as MP 120 °C. Specific optical rotation +12.3 deg at 22 °C/D. Solubility at 25 °C (g/100g solvent): water 512; ethanol 0.75; ether 0.4; DMSO /dimethyl sulfoxide/ 233; DMF /dimethyl formamid/ 39; at 50 °C: water 512; ethanol 0.88; at 75 °C: water 917 /Lactitol monohydrate/

Lactitol is stable under humid conditions. It is stable to heat and does not take part in the Maillard reaction.

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Food labeling. Health claims: dietary noncariogenic carbohydrate sweeteners and dental caries. ... Eligible noncariogenic carbohydrate sweeteners are the sugar alcohols xylitol, sorbitol, mannitol, maltitol, isomalt, lactitol, hydrogenated starch hydrolysates, hydrogenated glucose syrups, and erythritol, or a combination of these.

Engineering controls such as exhaust ventilation are recommended.|When working with small quantities in a well-ventilated area, respiratory protection may not be required. The use of an approved dust mask is recommended.

Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.|This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.|As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|/Wear/ chemically compatible gloves, /and/ safety glasses or goggles. Protect exposed skin.

Lactitol was among the many drugs tested for to establish the nature and amount of pharmacologically active substances which come into German landfills as a result of throwing away old drugs(1).

The LD50 is 23 g/kg in mice and >30 g/kg in rats. Experience with acute overdosage is limited, but is likely to involve significant gastrointestinal upset and diarrhea consistent with the pharmacologic profile of lactitol. Overdosage should be managed with symptomatic and supportive measures, where necessary.

LD50 Rat dermal >4,500 mg/kg bw|LD50 Rat oral > 10,000 mg/kg bw|LD50 Rat oral 30 g/kg|LD50 Mouse oral >23 g/kg

As it undergoes little-to-no systemic absorption, lactitol is unlikely to be subject to protein binding.

Lactitol does not occur in nature(1).

Lactitol's production and use as a sweetener in food(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 66(SRC), determined from a structure estimation method(2), indicates that lactitol is expected to have high mobility in soil(SRC). Volatilization of lactitol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.4X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Lactitol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.5X10-16 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Lactitol exhibits high stability towards microbial degradation(5).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 66(SRC), determined from a structure estimation method(2), indicates that lactitol 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 8.4X10-22 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of -5.53(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Lactitol exhibits high stability towards microbial degradation(8).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), lactitol, which has an estimated vapor pressure of 6.5X10-16 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 lactitol may be removed from the air by wet or dry deposition(SRC). Lactitol 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).

Lactitol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Lactitol 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 3 was calculated in fish for lactitol(SRC), using an estimated log Kow of -5.53(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 lactitol can be estimated to be 66(SRC). According to a classification scheme(2), this estimated Koc value suggests that lactitol is expected to have high mobility in soil.

The Henry's Law constant for lactitol is estimated as 8.4X10-22 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that lactitol is expected to be essentially nonvolatile from water and soil surfaces(2). Lactitol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.5X10-16 mm Hg(SRC), determined from a fragment constant method(3).

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

Lactitol is indicated for the treatment of chronic idiopathic constipation in adults.|FDA Label

Sugar Alcohols; Cathartics; Sweetening Agents|Lactitol (beta-galactosido-sorbitol) has been recently compared with lactulose for the treatment of chronic hepatic encephalopathy in a few studies, each comprising a small number of patients. The results are controversial. We studied the efficiency and tolerance of both compounds by using a meta-analysis on the basis of published controlled trials. /This/ study only included controlled or randomized trials comprising cirrhotic patients with chronic hepatic encephalopathy. Analyzed parameters were the portosystemic encephalopathy index of Conn after treatment, the percentage of improved patients and the percentage of patients who had ill effects related to the treatment (flatulence, diarrhea). Bibliographical screening revealed five studies comparing the effects of lactitol and lactulose in chronic hepatic encephalopathy. Four crossover studies were done that included 48 patients and one parallel study that included 29 patients. The duration of the treatment ranged from 3 to 6 mo. All studies found a similar efficiency with both drugs. However, they exhibited some discrepancies in the relative frequency of adverse reactions (flatulence). Meta-analysis showed no statistical differences in the portosystemic encephalopathy index after lactitol or lactulose treatment. The percentage of improved patients after lactitol or lactulose was similar. In contrast, the analysis revealed a higher frequency (p less than 0.01) of flatulence in patients treated with lactulose compared with those treated with lactitol. In conclusion, this meta-analysis shows no statistical difference between therapeutic effects of lactitol and lactulose, but it does show a higher frequency of flatulence with lactulose. This suggests that lactitol should be preferred to lactulose for the treatment of chronic hepatic encephalopathy.|Preliminary data suggest that lactitol (beta-galactoside-sorbitol), a new synthetic non-absorbable disaccharide, has beneficial effects on chronic portal systemic encephalopathy. To compare the efficacy of lactitol vs. lactulose in the treatment of acute portal systemic encephalopathy (PSE), 40 cirrhotic patients with an acute episode of PSE were randomly allocated to one of two groups: group A (20 patients) received lactulose (30 mL/6 hr) and group B (20 patients) lactitol (12 g/6 hr). These doses were adjusted daily to obtain two bowel movements per day. The duration of treatment was 5 days. Age, sex, hepatic and renal function, precipitating factors and level of PSE measured by clinical examination, EEG and number connection test were similar in the two groups. A complete clinical resolution of PSE occurred in 11 patients in each group. In 5 patients of the lactulose group and in 6 of the lactitol group there was a moderate improvement of PSE during the study. Finally, 4 patients in the lactulose group and 3 in the lactitol group did not respond to treatment. No side effects attributable to therapy were observed in either group. These results indicate that lactitol is as effective as lactulose in the management of patients with cirrhosis and acute PSE.

Lactitol helps to facilitate bowel movements by drawing water into the gastrointestinal tract. The oral administration of lactitol may reduce the absorption of concomitant medications - other oral medications should be administered at least 2 hours before or 2 hours after lactitol.

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.)|Agents that are used to stimulate evacuation of the bowels. (See all compounds classified as Cathartics.)

In healthy subjects under fed conditions, oral administration of 20 grams of lactitol resulted in a mean T_max of 3.6 ± 1.2 hours, C_max of 776 ± 253 ng/mL, and a mean AUC of 6,019 ± 1,771 ng*hr/mL.|Lactitol is not absorbed in the gastrointestinal tract to any significant extent. The vast majority of an ingested dose is likely degraded into organic acids in the colon and eliminated in the feces.|Data regarding the volume of distribution of lactitol are unavailable.|Data regarding the clearance of lactitol are unavailable.|Three male rats (150-200 g; six to eight weeks of age; one not pretreated and two habituated to a diet containing 7% lactitol) were orally intubated with about 2 mg D-(sorbitol-1-(14)C) lactitol. In the studies with the rats habituated to lactitol, 9-15% of the radioactivity was recovered from the air exhaled in the period 0-5 hours and 48% from the air exhaled in the period 0-24 hours. The urine and the feces contained a minor proportion of the administered radioactivity (urine, 2.3% after five hours and 6.8% after 24 hours; feces, 11.7% after 24 hours). The gastrointestinal tract contained 33% of the radioactivity after five hours and 5% after 24 hours; the remainder of the body contained 20% after five hours and 9% after 24 hours. It was concluded that lactitol is extensively degraded in the rat after oral administration presumably mainly by the intestinal microflora and that habituation of the rats to unlabelled lactitol did not essentially affect the rate and extent of degradation.|In studies designed to investigate the metabolism of erythritol in vivo in healthy volunteers and to compare the fermentation of erythritol by human fecal flora in vitro with that of glucose and lactitol, four male and two female volunteers aged 21-25 undertook an overnight fast and were then chosen at random to receive a single dose of 25 g (13)C-erythritol, (13)C-glucose, and (13)C-lactitol in 250 mL of water with at least three days between each treatment. Breath samples were taken for analysis of (13)C-carbon dioxide and hydrogen gas before treatment and at 30 min intervals up to 6 hr after treatment. The ratio of (13)C: (12)C-carbon dioxide was measured by isotope-ratio mass spectrometry. Urine samples were collected over 0-6 and 6-24 hr after treatment, and the erythritol and lactitol concentrations in urine were measured by HPLC. ... During the first 6 and 24 hr after dosing, 52 and 84%, respectively, of the administered erythritol was recovered in the urine. No increase in expired (13)C-carbon dioxide or hydrogen gas was observed, indicating that no fermentation had occurred in the gut. In contrast, there was a rapid increase in expired (13)C-carbon dioxide after consumption of glucose and a more gradual rise after ingestion of lactitol. Excretion of hydrogen gas in expired air was also increased after treatment with lactitol. Neither lactitol nor glucose was detected in significant amounts in the urine. ...|The gastrointestinal absorption of lactitol has been studied in 6 healthy volunteers and 8 patients with cirrhosis. Following administration of lactitol 0.5 g/kg, no lactitol was found in serum. The urinary excretion of lactitol over 24 hr ranged from 0.1 to 1.4% of the administered dose (0.46% in cirrhotics and 0.35% in healthy volunteers). Blood D- and L-lactate and plasma glucose did not increase following lactitol. The data indicate that lactitol was poorly absorbed from the gastrointestinal tract in healthy volunteers and patients with cirrhosis, and that the disaccharide did not disturb glucose or lactate homeostasis.|The fate of orally ingested lactitol, a non-absorbed sugar, was measured in six healthy human subjects by following the three routes of disposal of universally (14)C-labelled sugar. Lactitol was given as a 20 g daily dose to six healthy volunteers for 14 days and on the seventh day, 10 muCi of L-[U-(14)C]-lactitol was given with the unlabelled sugar and excretion of the (14)C in breath, urine and faeces was followed. The peak of (14)CO2 excretion occurred at six hours and total (14)CO2 accounted for 62.9 (5.0)% of isotope given, whilst 6.5 (3.6)% and 2.0 (0.3)% of the label were recovered from faeces and urine respectively. These data suggest that lactitol is extensively metabolised in the human colon and that a significant proportion of the bacterial metabolites are available for colonic absorption. Calculation revealed that 54.5% of the theoretical energy content of this compound was utilised by the subjects. ...

As it undergoes little-to-no systemic absorption, lactitol is unlikely to undergo any significant degree of metabolism.|In studies designed to investigate the metabolism of erythritol in vivo in healthy volunteers and to compare the fermentation of erythritol by human fecal flora in vitro with that of glucose and lactitol, four male and two female volunteers aged 21-25 undertook an overnight fast and were then chosen at random to receive a single dose of 25 g (13)C-erythritol, (13)C-glucose, and (13)C-lactitol in 250 mL of water with at least three days between each treatment. Breath samples were taken for analysis of (13)C-carbon dioxide and hydrogen gas before treatment and at 30 min intervals up to 6 hrs after treatment. The ratio of (13)C: (12)C-carbon dioxide was measured by isotope-ratio mass spectrometry. ... In order to maintain a constant metabolic rate, the subjects remained at rest during the study. For the assay of fermentation in vitro, fecal samples were collected from six healthy volunteers (sex and age not specified) who ate a normal western diet. None of the subjects complained of gastrointestinal symptomsand none had used antibiotics in the past six months. The samples were incubated under anaerobic conditions for 6 hr, and then the hydrogen gas concentration was measured in the head-space of the incubation vials. ... After a 6 hr incubation with erythritol, the amount of hydrogen gas formed by the fecal flora was comparable to that in control vials, but significantly (p < 0.001) more hydrogen gas was produced in the glucose and lactitol vials than in either control or erythritol.

The average half-life of orally administered lactitol is 2.4 hours.

Lactitol is an osmotic laxative - it exerts its pharmacologic effect by creating a hyperosmotic environment within the small intestine. The osmotic effect generated by lactitol draws water into the small intestine, which loosens stools and ultimately facilitates bowel movements.|Lactitol, an unabsorbed sugar with defined laxative threshold and superior taste properties has been suggested as an alternative to lactulose in the treatment of hepatic encephalopathy. In the present study /investigators/ compared the colonic metabolism of the two sugars using an in vitro fecal incubation system. Both sugars were readily metabolized by fecal bacteria producing volatile fatty acids and the metabolism was inhibited by neomycin. The effect of lactitol and lactulose on terminal ileal and colonic pH was monitored in six normal subjects using a radiotelemetry technique. Both sugars significantly lowered right colonic pH (basal -6.51 +/- 0.48 vs lactitol -5.63 +/- 0.50; lactulose -5.18 +/- 0.82, p less than 0.05). The pH of rest of the colon and terminal ileum was unaffected. Neomycin given concurrently with lactulose abolished acidification of right colon. As lactitol and lactulose have similar effects within the colon, lactitol would appear to have a role in the treatment of hepatic encephalopathy. As neomycin antagonizes the effect of lactulose in the colon, its concurrent use may be less effective in the treatment of hepatic encephalopathy.|... Reports from authoritative bodies and reviews indicates that the decrease in pH in plaque as a consequence of metabolic acid production by saccharolytic bacteria when exposed to fermentable carbohydrates (i.e. sugars and starches) may promote demineralization and prevent remineralization of the hydroxyapatite crystals. Tooth hydroxyapatite crystals are very resistant to dissolution at neutral pH, but their solubility drastically increases as pH drops. Typically, the critical pH for dental enamel is around 5.5. ... Demineralization of tooth tissues can also occur as a result of consumption of dietary acids in foods or beverages, and that frequent consumption can lead to dental erosion. Xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt, erythritol, D-tagatose, isomaltulose, sucralose and polydextrose are slowly metabolized by bacteria in the mouth. The rate and amount of acid production from these food constituents is significantly less than that from sucrose. ... Xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt, erythritol, D-tagatose, isomaltulose, sucralose and polydextrose do not promote dental caries because they do not lower plaque pH to the level associated with enamel demineralization. ... A cause and effect relationship has been established between the consumption of sugar-containing foods/drinks at an exposure frequency of four times daily or more and an increased tooth demineralization, and that the consumption of foods/drinks containing xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt, erythritol, D-tagatose, isomaltulose, sucralose or polydextrose, instead of sugar in sugar-containing foods/drinks, may maintain tooth mineralization by decreasing tooth demineralization compared with sugar-containing foods, provided that such foods/drinks do not lead to dental erosion.|The food constituents xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt, erythritol, D-tagatose, isomaltulose, sucralose or polydextrose resulted in reduced post-prandial blood glucose (or insulinemic) responses compared with sugars on a weight by weight basis owing to their reduced/delayed digestion/absorption and/or to a decrease in the amount of available carbohydrates, and that the consumption of foods/drinks in which xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt, erythritol, D-tagatose, isomaltulose, sucralose or polydextrose replaced sugars induced lower post-prandial glycemic and insulinemic responses than sugar-containing foods/drinks. ... A cause and effect relationship has been established between the consumption of foods/drinks containing xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt, erythritol, D-tagatose, isomaltulose, sucralose or polydextrose instead of sugar and reduction in post-prandial blood glucose responses (without disproportionally increasing post-prandial insulinemic responses) as compared to sugar-containing foods/drinks.

/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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Higher alcohols (>3 carbons) and related compounds/|/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 necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Monitor for pulmonary edema 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. Administer activated charcoal ... . /Higher alcohols (>3 carbons) and related compounds/|/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 ... . 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 (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Monitor for signs of hypoglycemia (decreased LOC, tachycardia, pallor, dilated pupils, diaphoresis, and/or dextrose strip or glucometer readings below 50 mg) and administer 50% dextrose if necessary ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Higher alcohols (>3 carbons) and related compounds/

/HUMAN EXPOSURE STUDIES/ Loading tests with equal amounts of sucrose, lactose, lactitol, and lactitol and sucrose have been carried out on eight healthy adults. The average maximal increases in blood glucose concentration after the different loadings were 63, 43, 6 and 40 mg% respectively. All subjects experienced diarrhea after lactitol (50 g) as well as lactitol and sucrose ingestion.|/HUMAN EXPOSURE STUDIES/ The chronic use of lactitol as a food additive or laxative might adversely affect calcium homeostasis. Its effect on calcium metabolism has been examined in an open cross-over study in 12 volunteers given 20-40 g lactitol per day for one month. Compared to a control period without lactitol, the disaccharide did not alter the urinary excretion of calcium, inorganic phosphate or hydroxyproline, nor did it alter the circulating levels of calcium, phosphate, alkaline phosphatase, parathormone and osteocalcin. Chronic treatment with lactitol in laxative doses had no measurable effect on calcium metabolism in man.|/HUMAN EXPOSURE STUDIES/ Lactitol, 24 g/day orally, was well tolerated by healthy or diabetic persons and it did not influence blood glucose and blood insulin levels. It did not induce diarrhea in diabetic patients.|/SIGNS AND SYMPTOMS/ If excessive amounts of bulk sweeteners (polyols) are consumed, laxative effects may occur.|For more Human Toxicity Excerpts (Complete) data for Lactitol (6 total), please visit the HSDB record page.

4-O-beta-D-galactopyranosyl-D-glucitol

Table of percent relative sweetness and caloric values: [Table#7906]|The sweetness of lactitol is 30-40% of that of sucrose.

Analysis of lactitol: method, HPLC.

Food additives|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Cosmetics -> Humectant; Skin conditioning

Food Additives -> SWEETENER; TEXTURIZER; THICKENER;