 | |||
| |||
| Names | |||
|---|---|---|---|
| Preferred IUPAC name Propane-1,2-diol | |||
Other names
| |||
| Identifiers | |||
3D model (JSmol) | |||
| ChEBI | |||
| ChEMBL | |||
| ChemSpider |
| ||
| ECHA InfoCard | 100.000.307 | ||
| EC Number |
| ||
| E number | E1520(additional chemicals) | ||
| KEGG | |||
| RTECS number |
| ||
| UNII |
| ||
| |||
| |||
| Properties | |||
| C3H8O2 | |||
| Molar mass | 76.095 g·mol−1 | ||
| Appearance | colourless liquid | ||
| Odor | odorless | ||
| Density | 1.036 g/cm3 | ||
| Melting point | −59 °C (−74 °F; 214 K) | ||
| Boiling point | 188.2 °C (370.8 °F; 461.3 K) | ||
| Miscible | |||
| Solubility inethanol | Miscible | ||
| Solubility indiethyl ether | Miscible | ||
| Solubility inacetone | Miscible | ||
| Solubility inchloroform | Miscible | ||
| logP | −1.34[2] | ||
| Vapor pressure | 10.66 Pa (20 °C) | ||
| Thermal conductivity | 0.34 W/m·K (50% H2O @ 90 °C (194 °F)) | ||
| Viscosity | 0.042 Pa·s | ||
| Thermochemistry | |||
| 189.9 J/(mol·K)[3] | |||
| Pharmacology | |||
| QA16QA01 (WHO) | |||
| Hazards | |||
| NFPA 704 (fire diamond) | |||
| Related compounds | |||
Relatedglycols | Ethylene glycol,1,3-propanediol | ||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Propylene glycol (IUPAC name:propane-1,2-diol) is aviscous, colorless liquid. It is almost odorless and has a faintly sweet taste. Itschemical formula is CH3CH(OH)CH2OH. As it contains twoalcohol groups, it is classified as adiol. Analiphatic diol may also be called aglycol. It ismiscible with a broad range of solvents, includingwater,acetone, andchloroform. In general, glycols[6] are non-irritating and have very lowvolatility.[7]
For certain uses as afood additive, propylene glycol is considered asGRAS by the USFood and Drug Administration, and is approved for food manufacturing.[8] In the European Union, it hasE-number E1520 for food applications. For cosmetics andpharmacology, the number is E490. Propylene glycol is also present inpropylene glycol alginate, which is known as E405.
Propylene glycol is approved and used as a vehicle for topical, oral, and some intravenous pharmaceutical preparations in the US and Europe.
The compound is sometimes called (alpha)α-propylene glycol to distinguish it from theisomerpropane-1,3-diol, known as (beta) β-propylene glycol. Propylene glycol is chiral. Commercial processes typically use theracemate. The S-isomer is produced by biotechnological routes.
Industrially, propylene glycol is mainly produced frompropylene oxide (for food-grade use). According to a 2018 source, 2.16 M tonnes are produced annually.[7] Manufacturers use either non-catalytic high-temperature process at 200 °C (392 °F) to 220 °C (428 °F), or a catalytic method, which proceeds at 150 °C (302 °F) to 180 °C (356 °F) in the presence ofion exchange resin or a small amount of sulfuric acid or alkali.[9]
Final products contain 20% propylene glycol, 1.5% ofdipropylene glycol, and small amounts of otherpolypropylene glycols.[10] Further purification produces finished industrial grade or USP/JP/EP/BP grade propylene glycol that is typically 99.5% or greater. Use of USP (US Pharmacopoeia) propylene glycol can reduce the risk of Abbreviated New Drug Application (ANDA) rejection.[11]
Propylene glycol can also be obtained fromglycerol, a byproduct from the production ofbiodiesel.[7] This starting material is usually reserved for industrial use because of the noticeable odor and taste that accompanies the final product.
(S)-Propanediol is synthesized via fermentation methods.Lactic acid andlactaldehyde are common intermediates.Dihydroxyacetone phosphate, one of the two products of breakdown (glycolysis) offructose 1,6-bisphosphate, is a precursor tomethylglyoxal. This conversion is the basis of a potential biotechnological route to the commodity chemical1,2-propanediol. Three-carbondeoxysugars are also precursor to the 1,2-diol.[7]
A small-scale, nonbiological route fromD-mannitol is illustrated in the following scheme:[12]
-Propanediol_from_D-Mannitol.png)
Forty-five percent of propylene glycol produced is used as a chemical feedstock for the production of unsaturatedpolyester resins. In this regard, propylene glycol reacts with a mixture of unsaturatedmaleic anhydride andisophthalic acid to give acopolymer. This partially unsaturated polymer undergoes furthercrosslinking to yieldthermoset plastics. Related to this application, propylene glycol reacts with propylene oxide to giveoligomers and polymers that are used to producepolyurethanes.[7] Propylene glycol is used in water-based acrylic architectural paints to extend dry time which it accomplishes by preventing the surface from drying due to its slower evaporation rate compared to water.
In regulated amounts, propylene glycol is designated as safe for food manufacturing as ananticaking agent,emulsifier, flavor agent,humectant, texturizer,stabilizer,solvent,antioxidant,antimicrobial agent, andthickener.[8][13][14]
As regulated by the US FDA for substances deemed as GRAS, propylene glycol is "not subject to premarket review and approval by FDA because it is generally recognized, by qualified experts, to be safe under the intended conditions of use."[13] The scientific panel evaluating propylene glycol for food manufacturing defined its conclusion as: "There is no evidence in the available information on [propylene glycol] that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future."[13]
The FDA law defined maximum limits for the use of propylene glycol in various food categories undergood manufacturing practices:[8]
TheEuropean Food Safety Authority authorizes propylene glycol for use in food manufacturing, establishing a safe daily intake of 25 mg per kg of body weight.[15] Specifically for ice cream orice milk products,Health Canada permits use of propylene glycol mono fatty acid esters as an emulsifier and stabilizer at a maximum level of use of 0.35% of the ice cream made from the ingredients mix.[16]
Propylene glycol is used in a variety of other edible items, such as baked goods, desserts, prepared meals, flavoring mixes, candy, popcorn, whipped dairy products, and soda.[17] It is also used in beer to stabilize the foam.[18]
Vaporizers used for delivery of pharmaceuticals or personal-care products often include propylene glycol among the ingredients.[7] In alcohol-based hand sanitizers, it is used as a humectant to prevent the skin from drying.[19] Propylene glycol is used as asolvent in manypharmaceuticals, includingoral,injectable, andtopical formulations. Many pharmaceutical drugs which areinsoluble in water utilize propylene glycol as a solvent and carrier;benzodiazepine tablets are one example.[20] Propylene glycol is also used as a solvent and carrier for many pharmaceuticalcapsule preparations. Additionally, certain formulations ofartificial tears use propylene glycol as an ingredient.[21]
.jpg)
Thefreezing point of water is depressed when mixed with propylene glycol. It is used as aircraftde-icing and anti-icing fluid. A 50% water-diluted and heated solution is used for removal of icing accretions from the fuselages of commercial aircraft on the ground (de-icing), and 100% undiluted cold solution is used only on wings and tail surfaces of an aircraft in order to prevent ice accretion from forming during a specific period of time before takeoff (anti-icing). Normally, such time-frame is limited to 15–90 minutes, depending on the severity of snowfall and outside air temperature.[7][22] Water-propylene glycol mixtures dyed pink to indicate the mixture is relatively nontoxic are sold under the name ofRV or marine antifreeze. Propylene glycol is frequently used as a substitute forethylene glycol in low toxicity, environmentally friendly automotiveantifreeze. It is also used to winterize the plumbing systems in vacant structures.[23] Theeutectic composition/temperature is 60:40 propylene glycol:water/−60 °C.[24][25] The −50 °F/−45 °C commercial product is, however, water rich; a typical formulation is 40:60.[26]
Propylene glycol, vegetableglycerin,[27] or a mixture of both, are the main ingredients ine-liquid used inelectronic cigarettes. They areaerosolized to resemble smoke and serve as carriers for substances such asnicotine andflavorants.[28]
When used in average quantities, propylene glycol has no measurable effect on development and/or reproduction on animals and probably does not adversely affect human development or reproduction without active use.[37] Thesafety of electronic cigarettes—which utilize propylene glycol-based preparations of nicotine or THC and other cannabinoids—is the subject of much controversy.[38][39][40]Vitamin E acetate has also been identified in this controversy.[41]
The acute oral toxicity of propylene glycol is very low, and large quantities are required to cause perceptible health effects in humans;[13] in fact, the toxicity of propylene glycol is one third that ofethanol.[42] Propylene glycol is metabolized in the human body intopyruvic acid (a normal part of the glucose-metabolism process, readily converted to energy),acetic acid (handled by ethanol-metabolism),lactic acid (a normal acid generally abundant during digestion),[43] andpropionaldehyde (a potentially hazardous substance).[44][45][46] According to theDow Chemical Company, theLD50 (dose that kills 50% of the test population) for rats is 20 g/kg (oral/rat).[47][48]
Toxicity generally occurs at plasma concentrations over 4 g/L, which requires extremely high intake over a relatively short period of time, or when used as a vehicle for drugs or vitamins given intravenously or orally in largebolus doses.[49] It would be nearly impossible to reach toxic levels by consuming foods or supplements, which contain at most 1 g/kg of PG, except for alcoholic beverages in the US which are allowed 5 percent = 50 g/kg.[8][13] Cases of propylene glycol poisoning are usually related to either inappropriate intravenous administration or accidental ingestion of large quantities by children.[50]
The potential for long-term oral toxicity is also low.[51] In aNational Toxicology Program continuous breeding study, no effects on fertility were observed in male or female mice that received propylene glycol in drinking water at doses up to 10100 mg/kg bw/day. No effects on fertility were seen in either the first or second generation of treated mice.[37] In a 2-year study, 12 rats were provided with feed containing as much as 5% propylene glycol, and showed no apparent ill effects.[52]
.jpg)
Propylene glycol may be non-irritating to the skin, see sectionAllergic reaction below for details on allergic reactions.[53] Undiluted propylene glycol is minimally irritating to the eye, producing slight transientconjunctivitis; the eye recovers after the exposure is removed.
A 2018 human volunteer study found that 10 male and female subjects undergoing 4 hours exposures to concentrations of up to 442 mg/m3 and 30 minutes exposures to concentrations of up to 871 mg/m3 in combination with moderate exercise did not show pulmonary function deficits, or signs of ocular irritation, with only slight symptoms of respiratory irritation reported.[54]
Propylene glycol has not causedsensitization or carcinogenicity in laboratory animal studies, nor has it demonstratedgenotoxic potential.[55][56]
Inhalation of propylene glycol vapors appears to present no significant hazard in ordinary applications.[57] Due to the lack of chronic inhalation data, it is recommended that propylene glycol not be used in inhalation applications such as theatrical productions, or antifreeze solutions for emergencyeye wash stations.[58] Recently, propylene glycol (commonly alongsideglycerol) has been included as a carrier for nicotine and other additives ine-cigarette liquids, the use of which presents a novel form of exposure. The potential hazards of chronic inhalation of propylene glycol or the latter substance as a whole are as-yet unknown.[59]
According to a 2010 study, the concentrations of PGEs (counted as the sum of propylene glycol andglycol ethers) in indoor air, particularly bedroom air, has been linked to increased risk of developing numerous respiratory and immune disorders in children, includingasthma,hay fever,eczema, and allergies, with increased risk ranging from 50% to 180%. This concentration has been linked to use of water-based paints and water-based system cleansers. However, the study authors write thatglycol ethers and not propylene glycol are the likely culprit.[60][61][62]
Studies with intravenously administered propylene glycol have resulted in LD50 values in rats and rabbits of 7 mL/kg BW.[63] Ruddick (1972) also summarized intramuscular LD50 data for rat as 13–20 mL/kg BW, and 6 mL/kg BW for the rabbit. Adverse effects tointravenous administration of drugs that use propylene glycol as anexcipient have been seen in a number of people, particularly with large bolus dosages. Responses may include CNS depression, "hypotension,bradycardia,QRS andT abnormalities on the ECG,arrhythmia, cardiac arrhythmias, seizures, agitation, serumhyperosmolality,lactic acidosis, andhaemolysis".[64] A high percentage (12–42%) of directly-injected propylene glycol is eliminated or secreted in urine unaltered depending on dosage, with the remainder appearing in itsglucuronide-form. The speed ofrenal filtration decreases as dosage increases,[65] which may be due to propylene glycol's mild anesthetic /CNS-depressant properties as an alcohol.[66] In one case, intravenous administration of propylene glycol-suspendednitroglycerin to an elderly man may have induced coma andacidosis.[67] However, no confirmed lethality from propylene glycol was reported.
Propylene glycol is an approved food additive for dog andsugar glider food under the category of animal feed and isgenerally recognized as safe for dogs,[68] with an LD50 of 9 mL/kg. The LD50 is higher for most laboratory animals (20 mL/kg).[69] However, it is prohibited for use in food for cats due to links toHeinz body formation and a reduced lifespan of red blood cells.[70] Heinz body formation from MPG has not been observed in dogs, cattle, or humans.
Estimates on the prevalence of propylene glycol allergy range from 0.8% (10% propylene glycol in aqueous solution) to 3.5% (30% propylene glycol in aqueous solution).[71][72][73] The North American Contact Dermatitis Group (NACDG) data from 1996 to 2006 showed that the most common site for propylene glycolcontact dermatitis was the face (25.9%), followed by a generalized or scattered pattern (23.7%).[71] Investigators believe that the incidence of allergic contact dermatitis to propylene glycol may be greater than 2% in patients witheczema or fungal infections, which are very common in countries with lesser sun exposure and lower-than-normalvitamin D balances. Therefore, propylene glycol allergy is more common in those countries.[74][improper synthesis?]
Because of its potential for allergic reactions and frequent use across a variety of topical and systemic products, propylene glycol was named the American Contact Dermatitis Society'sAllergen of the Year for 2018.[75][76] Recent publication from The Mayo Clinic reported 0.85% incidence of positive patch tests to propylene glycol (100/11,738 patients) with an overall irritant rate of 0.35% (41/11,738 patients) during a 20-year period of 1997–2016.[77] 87% of the reactions were classified as weak and 9% as strong. The positive reaction rates were 0%, 0.26%, and 1.86% for 5%, 10%, and 20% propylene glycol respectively, increasing with each concentration increase. The irritant reaction rates were 0.95%, 0.24%, and 0.5% for 5%, 10%, and 20% propylene glycol, respectively. Propylene glycol skin sensitization occurred in patients sensitive to a number of other concomitant positive allergens, most common of which were: Myroxylon pereirae resin, benzalkonium chloride, carba mix, potassium dichromate, neomycin sulfate; for positive propylene glycol reactions, the overall median of 5 and mean of 5.6 concomitant positive allergens was reported.
Propylene glycol occurs naturally, probably as the result of anaerobic catabolism of sugars in the human gut. It is degraded byvitamin B12-dependent enzymes, which convert it topropionaldehyde.[78]
Propylene glycol is expected to degrade rapidly in water from biological processes, but is not expected to be significantly influenced by hydrolysis, oxidation,volatilization,bioconcentration, oradsorption to sediment.[55] Propylene glycol is readily biodegradable under aerobic conditions in freshwater, in seawater and in soil. Therefore, propylene glycol is considered as not persistent in the environment.
Propylene glycol exhibits a low degree of toxicity toward aquatic organisms. Several guideline studies available for freshwater fish with the lowest observed lethal concentration of 96-hLC50 value of 40,613 mg/L in a study withOncorhynchus mykiss. Similarly, the lethal concentration determined in marine fish is a 96-h LC50 of >10,000 mg/L inScophthalmus maximus.
Although propylene glycol has low toxicity, it exerts high levels ofbiochemical oxygen demand (BOD) during degradation in surface waters. This process can adversely affect aquatic life by consuming oxygen needed by aquatic organisms for survival. Large quantities ofdissolved oxygen (DO) in thewater column are consumed whenmicrobial populations decompose propylene glycol.[79]: 2–23
air containing these vapors in amounts up to the saturation point is completely harmless
