Polyoxyethylene sorbitan monolaurate

346.459991455078

604.418640

500-018-3

DTXSID3031949

Lemon- to amber-colored liquid

34021300

133.14000

5.37

Amber viscous liquid

1.1±0.1 g/cm3

98.9 °C (decomp)

100 °C

>230 °F

1.502

100 g/L

0-6°C

<1.4 hPa (20 °C)

LD50 orally in Rabbit: 38900 mg/kg

Characteristic odor

Bitter

NONH for all modes of transport

1

22-36/37/38-37/38-41

24/25-36/37/39-36-26

TR7400000

Xi

Stable. Incompatible with strong oxidizing agents.

P261, P264, P272, P280, P302+P352, P305+P351+P338, P321, P333+P313, P337+P313, P363, P501

H317

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.

Aqueous solutions of Polysorbate 20 undergo autoxidation on storage at room temperature, with changes in the peroxide number, pH, surface tension, and cloud point. Autoxidation is accelerated by light, elevated temperature, and copper sulfate. Hydrolysis of Polysorbate 20 also occurs at room temperature, whereas the oxyethylene moieties undergo chain shortening at temperatures above 40 °C.|Discoloration and/or precipitation occur with various substances, especially phenols, tannins, tars, and tarlike materials. The antimicrobial activity of paraben preservatives is reduced in the presence of polysorbates.

Polysorbate 20 is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and 2) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.|Polysorbate 20 is an indirect food additive for use only as a component of adhesives.|The substances listed in paragraph (c) of this section may be safely used as emulsifiers and/or surface-active agents in the manufacture of articles or components of articles intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food, subject to the provisions of this section. Polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate) meeting the following specifications: Saponification number 40-50, acid number 0-2, hydroxyl number 60-108, oxyethylene content 70-74 percent is included on this list.

Not Classified

Eye protection and gloves are recommended.

Human skin irritant.

Nonionic surfactants are commonly used as excipients in pharmaceutical formulation, but recent studies demonstrate that the ingredients affect the pharmacokinetics of the active drugs. However, the mechanisms are largely unknown. Here, ... the effects of four common nonionic surfactants polysorbate 20, polyoxyl 35 castor oil, polyoxyl 40 stearate and poloxamer 188, on cytochrome P450 3A /were examined/ in vitro and in vivo using midazolam as a probe. ... The effects of these surfactants on the 1'-hydroxylation of midazolam /were examined/ in isolated rat liver and intestinal microsomes. All the surfactants tested inhibited midazolam 1'-hydroxylation in a concentration-dependent manner and presented a mixed competitive inhibitory model with decreased V(max) and increased K(m) values in vitro. Among the tested nonionic surfactants, polysorbate 20 was the most potent inhibitor of midazolam 1'-hydroxylation with an IC(50) of 2.06 and 0.39mg/mL in the liver and intestinal microsomes, respectively. These surfactants were also tested in vivo ... on the pharmacokinetics of midazolam in rats. These four surfactants displayed different inhibitory patterns in terms of the AUC of midazolam and 1'-hydroxymidazolam. Polysorbate 20 significantly increased both AUC(0-4 hr) and AUC(0-infinity) of midazolam and decreased the AUC(0-4 hr) of 1'-hydroxymidazolam to about 40% (p<0.05) in both single- and multiple-treated rats, along with a significant decrease of the metabolic ratio of 1'-hydroxymidazolam/midazolam to 25%. Polyoxyl 35 castor oil, polyoxyl 40 stearate and poloxamer 188 displayed complicated inhibition on the 1'-hydroxylation of midazolam dependent on the administration formula. These results confirmed that effects of these surfactants would have potential inhibitory effects on cytochrome P450 3A and altered midazolam bioavailability. Therefore, caution is needed when selecting nonionic surfactants in drug formulation.

LD50 Rat oral 37,000 mg/kg|LD50 Rat ip 3850 mg/kg|LD50 Rat iv 770 mg/kg|LD50 Mouse oral >25 g/kg|For more Non-Human Toxicity Values (Complete) data for Polysorbate 20 (8 total), please visit the HSDB record page.

According to the 2006 TSCA Inventory Update Report, the number of persons reasonably likely to be exposed in industrial manufacturing, processing, and use of polysorbate 20 is 1 to 99; the data may be greatly underestimated(1).|NIOSH (NOES Survey 1981-1983) has statistically estimated that 161,625 workers (125,776 of these were female) were potentially exposed to polysorbate 20 in the US(1).

The polysorbates are used in pharmaceuticals for various reasons, including the modification of an active ingredient's absorption. ... Polysorbates 20 and 80 are listed as welling or clarifying agents in ophthalmic products and as cleaning, wetting, or solvent agents for contact lenses in concentrations not to exceed 1.0 percent. Polysorbate 20 is classified as an "inactive ingredient or pharmaceutical necessity" in topical analgesic, antirheumatic, otic, burn, and sunburn treatment/prevention products.|Polysorbates 20 and 80 (Tween 20 and Tween 80) are used in the formulation of biotherapeutic products for both preventing surface adsorption and as stabilizers against protein aggregation. The polysorbates are amphipathic, nonionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan being polyoxyethylene sorbitan monolaurate for polysorbate 20 and polyoxyethylene sorbitan monooleate for polysorbate 80. The polysorbates used in the formulation of biopharmaceuticals are mixtures of different fatty acid esters with the monolaurate fraction of polysorbate 20 making up only 40-60% of the mixture and the monooleate fraction of polysorbate 80 making up >58% of the mixture. The polysorbates undergo autooxidation, cleavage at the ethylene oxide subunits and hydrolysis of the fatty acid ester bond. Autooxidation results in hydroperoxide formation, side-chain cleavage and eventually formation of short chain acids such as formic acid all of which could influence the stability of a biopharmaceutical product...|The synthesis, the physicochemical characterization and the biological evaluation of three novel pH-sensitive systems prepared derivatizing polysorbate 20 (Tween 20) with glycine, N-methyl-glycine and N,N-dimethyl-glycine (TW20-GLY, TW20-MMG and TW20-DMG) /is described/. These derivatives form pH-sensitive vesicles and translocate small molecules into cells. The reported systems are efficient drug delivery systems for human hepatoblastoma cells.|/Experimental Therapy/ /Investigators/ studied the effects of Polysorbates 20 and 80 in 13 patients with bile salt-deficient steatorrhea, 8 of whom received Polysorbate 80 and 5 Polysorbate 20. When 2 g were administered three times a day, the Polysorbates increased micellization of ingested fat and improved fat absorption. Therapy reduced steatorrhea in 10 of the 13 patients.

Polysorbates have ... been associated with serious adverse effects, including some deaths, in low-birthweight infants intravenously administered a vitamin E preparation containing a mixture of Polysorbates 20 and 80.

Agents that modify interfacial tension of water; usually substances that have one lipophilic and one hydrophilic group in the molecule; includes soaps, detergents, emulsifiers, dispersing and wetting agents, and several groups of antiseptics. (See all compounds classified as Surface-Active Agents.)|Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form. These include binders, matrix, base or diluent in pills, tablets, creams, salves, etc. (See all compounds classified as Excipients.)

/Investigators/ found that the labeled lauric acid moiety of Polysorbate 20 was rapidly absorbed and oxidized by rats. After 24 hours, some 75 percent of the lauric acid was oxidized and expired as CO2. 4 percent was not absorbed from the alimentary tract.|The polyoxyethylene sorbitan moiety left after hydrolysis of the ester is poorly absorbed from the rat's gastrointestinal tract. In one study with a radioactive carbon label in the polyoxyethylene portion of Polysorbate 20, 90 percent was excreted in the feces and 8 percent in the urine. No radioactivity was found in the liver, carcass, or expired C02.|After intravenous injection of Polysorbate 20 into rats, the distribution of the labeled lauric acid moiety was: expired CO2, 68 percent; carcass, 22 percent; urine, 5 percent; feces and gastrointestinal contents, 2.5 percent; and liver 0.7 percent. The distribution of the labeled polyoxyethylene moiety was: urine, 83 percent; feces, 11 percent; carcass, 2 percent; liver, 0.15 percent; and expired CO2 nil.|/Investigators/ fed Polysorbate 20 to rats and followed the distribution of labeled lauric acid to various tissues. The approximate distribution of radioactivity 24 hours after oral administration was: expired C02, 80 percent; carcass, 12 percent; unabsorbed from the gastrointestinal tract, 4 percent; urine, 2.5 percent; and liver, 1.2 percent.|For more Absorption, Distribution and Excretion (Complete) data for Polysorbate 20 (7 total), please visit the HSDB record page.

The metabolism of Polysorbates in rats has been studied in detail with 14C-label tracer techniques. When administered orally, the ester link of the Polysorbate molecule is hydrolyzed by pancreatic lipase, and the fatty acid moiety is released to be absorbed and metabolized as any other dietary fatty acid.|After intravenous injection into rats, the ester bond is hydrolyzed by blood lipases. When Polysorbate 20 was injected into rats, the labeled lauric acid moiety was metabolized and appeared mostly as expired CO2. The polyoxyethylene moiety was not catabolized, since no radioactivity was recovered as CO2 when this portion of the molecule was labeled. Most of the labeled polyoxyethylene appeared in the urine, but some was present in the feces, indicating biliary excretion.

The intravenous infusion of 5 mL of Polysorbate 20 at a rate of 0.2 mL/15 sec into 14 intact and 8 splenectomized dogs evoked anaphylactic-like symptoms that may have been mediated by endogenous histamine release. Histamine release was indicated by skin changes, tachyphylaxis, and protection by antihistamines. Other changes included decreased arterial pressure, heart rate, and plasma volume and increased respiratory rate, lymph flow, and hematocrit. The polysorbates have been shown to be nonspecific histamine releasers, and their hemodynamic effects are entirely compatible with histamine release. The later response of decreased output, hypotension, and tachycardia is almost indistinguishable from that found in endotoxic or hemorrhagic shock.|... The hemolytic action of Polysorbates 20, 40, 60, and 80 on human erythrocytes was measured and correlated with the physical properties of the surfactants. The hemolytic power depended on the mutual effect of the hydrophobic and hydrophilic fragments of the polysorbate molecule and did not depend on the hydrophile-lipophile balance as such. It was suggested that the role of the polyoxyethylene moiety in the action of the polysorbates on membranes lies with its effect on the relative lipophilicity of the compound. The polyoxyethylene fragment may have also interacted with surface components when the molecule was adsorbed onto the membrane. It was concluded that the lysis of erythrocytes by the polysorbates was caused not by the destruction of the membrane but by some rearrangement of the membrane structure accompanying adsorption of the surfactant.|The effects of the polysorbates on mitochondrial respiration seem to reflect a direct action on the ferrocytochrome C step in the electron transport chain of oxidative phosphorylation. The addition of Polysorbate 80 to suspensions of liver mitochondria from normal and tumor-bearing rats led to an increase in the activity of succinate-cytochrome C reductase in one study and an increase in the activity of cytochrome C oxidase in another. The activation of cytochrome C oxidase by the polysorbates is well documented. They have been shown to reversibly convert cytochrome oxidase from an inactive to an active coupling state by providing a suitable environment for the most active conformational state. This effect was pH independent when demonstrated with purified cytochrome oxidase.

Since the fatty acids used in the production of cosmetic ingredients frequently contain fatty acids other than the principal acid named, each of the Polysorbates may contain a complex fatty acid moiety. In a study on Polysorbates 20, 40, 60, and 80, 15 different fatty acids were detected.

/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/ The Draize-Shelanski tests included UV exposure after induction patches 1, 4, 7, and 10 and after the challenge patch. With products containing Polysorbates 20 and 60, there were few instances of irritation and no reactions indicative of photosensitization.|/HUMAN EXPOSURE STUDIES/ The UV light exposure was to a Hanovia Tanette Mark 1 quartz lamp at a distance of 12 inches for 1 minute. This lamp has a wavelength coverage of 240 to 370 nM with a peak at 265 nM. One of the 103 subjects in the Schwartz-Peck test on a product containing Polysorbate 20 showed a weak, nonvesicular reaction after a single UV exposure; the significance of this reaction was not interpreted.|/HUMAN EXPOSURE STUDIES/ Several product formulations containing the polysorbates have been tested for human skin sensitization on a total of 3481 subjects using a variety of testing methods. These studies included: four Schwartz-Peck prophetic patch tests on product formulations containing 0.3 to 2.4 percent Polysorbates 20, 60, or 80; four controlled-use tests on product formulations containing Polysorbate 85 at 1.0 percent or Polysorbates 60 and 80 at 2.5 percent each; 15 Draize-Shelanski repeated insult patch tests on product formulations containing 0.084 to 6.0 percent Polysorbates 20, 40, 60, or 80; and one Kligman maximization test on a product formulation containing 6.0 percent Polysorbate 20. Of the 3481 subjects reported, there were no reactions indicative of sensitization to any of the polysorbates.|/HUMAN EXPOSURE STUDIES/ The effect of Polysorbate 20 on corneal permeability to fluorescein was investigated in human subjects in an effort to find safe and effective agents that increase permeability to drugs. Subjects were normal volunteers of both sexes, aged 20 to 46 years. Single drops of Polysorbate 20 at various concentrations in saline were administered to one eye; the other eye served as a control. Polysorbate 20 caused no adverse effects on the eye at concentrations up to 40 percent.|For more Human Toxicity Excerpts (Complete) data for Polysorbate 20 (13 total), please visit the HSDB record page.

20s, Polysorbate

Armotan PML 20 /Formulation name/|Capmul POE-L /Formulation name/|Capmul POE-L Low PV /Formulation name/|Crillet 1 /Formulation name/|For more Formulations/Preparations (Complete) data for Polysorbate 20 (24 total), please visit the HSDB record page.

Sorbitan, monododecanoate, poly(oxy-1,2-ethanediyl) derivs.: ACTIVE|XU - indicates a substance exempt from reporting under the Chemical Data Reporting Rule, (40 CFR 711).

EPA Safer Chemical Functional Use Classes -> Surfactants|Safer Chemical Classes -> Green circle - The chemical has been verified to be of low concern|Food additives|Food Additives -> EMULSIFIER; -> JECFA Functional Classes|Cosmetics -> Emulsifying; Surfactant

Food Additives -> EMULSIFIER;