Propylene glycol

Structure

The compound is sometimes called (alpha) α-propylene glycol to distinguish it from the isomer propane-1,3-diol, known as (beta) β-propylene glycol. Propylene glycol is chiral. Commercial processes typically use the racemate. The S-isomer is produced by biotechnological routes.

Production

Industrial

Industrially, propylene glycol is mainly produced from propylene oxide (for food-grade use). According to a 2018 source, 2.16 M tonnes are produced annually.

Final products contain 20% propylene glycol, 1.5% of dipropylene glycol, and small amounts of other polypropylene glycols. 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.

Propylene glycol can also be obtained from glycerol, a byproduct from the production of biodiesel. This starting material is usually reserved for industrial use because of the noticeable odor and taste that accompanies the final product.

Laboratory

(S)-Propanediol is synthesized via fermentation methods. Lactic acid and lactaldehyde are common intermediates. Dihydroxyacetone phosphate, one of the two products of breakdown (glycolysis) of fructose 1,6-bisphosphate, is a precursor to methylglyoxal. This conversion is the basis of a potential biotechnological route to the commodity chemical 1,2-propanediol. Three-carbon deoxysugars are also precursor to the 1,2-diol.

A small-scale, nonbiological route from D-mannitol is illustrated in the following scheme:

Applications

Polymers

Forty-five percent of propylene glycol produced is used as a chemical feedstock for the production of unsaturated polyester resins. In this regard, propylene glycol reacts with a mixture of unsaturated maleic anhydride and isophthalic acid to give a copolymer. This partially unsaturated polymer undergoes further crosslinking to yield thermoset plastics. Related to this application, propylene glycol reacts with propylene oxide to give oligomers and polymers that are used to produce polyurethanes. 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.

Food and drug

In regulated amounts, propylene glycol is designated as safe for food manufacturing as an anticaking agent, emulsifier, flavor agent, humectant, texturizer, stabilizer, solvent, antioxidant, antimicrobial agent, and thickener.

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." 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."

The FDA law defined maximum limits for the use of propylene glycol in various food categories under good manufacturing practices:

• 2.0% for general food categories
• 2.5% for frozen dairy products
• 5% for alcoholic beverages
• 5% for nuts and nut products
• 24% for confections and frostings
• 97% for seasonings and flavorings

The European Food Safety Authority authorizes propylene glycol for use in food manufacturing, establishing a safe daily intake of 25 mg per kg of body weight. Specifically for ice cream or ice 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.

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. It is also used in beer to stabilize the foam.

Vaporizers used for delivery of pharmaceuticals or personal-care products often include propylene glycol among the ingredients. Propylene glycol is used as a solvent in many pharmaceuticals, including oral, injectable, and topical formulations. Many pharmaceutical drugs which are insoluble in water utilize propylene glycol as a solvent and carrier; benzodiazepine tablets are one example. Propylene glycol is also used as a solvent and carrier for many pharmaceutical capsule preparations. Additionally, certain formulations of artificial tears use propylene glycol as an ingredient.

Antifreeze

The freezing point of water is depressed when mixed with propylene glycol. It is used as aircraft de-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. Water-propylene glycol mixtures dyed pink to indicate the mixture is relatively nontoxic are sold under the name of RV or marine antifreeze. Propylene glycol is frequently used as a substitute for ethylene glycol in low toxicity, environmentally friendly automotive antifreeze. It is also used to winterize the plumbing systems in vacant structures. The eutectic composition/temperature is 60:40 propylene glycol:water/−60 °C. The −50 °F/−45 °C commercial product is, however, water rich; a typical formulation is 40:60.

Electronic cigarettes liquid

Propylene glycol, vegetable glycerin, or a mixture of both, are the main ingredients in e-liquid used in electronic cigarettes. They are aerosolized to resemble smoke and serve as carriers for substances such as nicotine and flavorants.

Miscellaneous applications

• As a solvent for many substances, both natural and synthetic.
• As a humectant (E1520).
• As a freezing point depressant for slurry ice.
• In veterinary medicine as an oral treatment for hyperketonaemia in ruminants.
• In the cosmetics industry, where propylene glycol is very commonly used as a carrier or base for various types of makeup.
• For trapping and preserving insects (including as a DNA preservative).
• For the creation of theatrical smoke and fog in special effects for film and live entertainment. So-called 'smoke machines' or 'hazers' aerosolize a mixture of propylene glycol and water to create the illusion of smoke. While many of these machines use a propylene-glycol–based fluid, some use oil or triethylene glycol. Those which use propylene glycol do so in a process that is identical to how electronic cigarettes work; utilizing a heating element to produce a dense fog. The fog produced by these machines has the aesthetic look and appeal of smoke, but without exposing performers and stage crew to the harms and odors associated with actual smoke.
• As an additive in polymerase chain reaction (PCR) to reduce the melting temperature of nucleic acids for targeting of GC rich sequences.
• As a surfactant, it is used to prevent water from beading up on objects. It is used in photography for this purpose to reduce the risk of water spots, or deposits of minerals from water used to process film or paper.
• As an ingredient in couplants for ultrasonic testing and medical ultrasound.

Safety in humans

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. The safety of electronic cigarettes—which use propylene glycol-based preparations of nicotine or THC and other cannabinoids—is the subject of much controversy. Vitamin E acetate has also been identified in this controversy.

Oral administration

The acute oral toxicity of propylene glycol is very low, and large quantities are required to cause perceptible health effects in humans; Propylene glycol is metabolized in the human body into pyruvic 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), and propionaldehyde (a potentially hazardous substance). According to the Dow Chemical Company, the LD50 (dose that kills 50% of the test population) for rats is 20 g/kg (oral/rat).

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 large bolus doses. It would be nearly impossible to reach toxic levels by consuming foods or supplements, which contain at most, by mass, one per mille of PG, except for alcoholic beverages in the US, which are allowed five percent by mass.

The potential for long-term oral toxicity is also low. In a National 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. In a two-year study, 12 rats were provided with feed containing as much as 5% propylene glycol, and showed no apparent ill effects.

Skin and eye contact

Propylene glycol may be non-irritating to the skin, see section Allergic reaction below for details on allergic reactions. Undiluted propylene glycol is minimally irritating to the eye, producing slight transient conjunctivitis; the eye recovers after the exposure is removed.

Propylene glycol has not caused sensitization or carcinogenicity in laboratory animal studies, nor has it demonstrated genotoxic potential.

Inhalation

Inhalation of propylene glycol vapors appears to present no significant hazard in ordinary applications. 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 emergency eye wash stations. Recently, propylene glycol (commonly alongside glycerol) has been included as a carrier for nicotine and other additives in e-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.

According to a 2010 study, the concentrations of PGEs (counted as the sum of propylene glycol and glycol ethers) in indoor air, particularly bedroom air, has been linked to increased risk of developing numerous respiratory and immune disorders in children, including asthma, 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 that glycol ethers and not propylene glycol are the likely culprit.

Intravenous administration

Studies with intravenously administered propylene glycol have resulted in LD50 values in rats and rabbits of 7 mL/kg BW. 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 to intravenous administration of drugs that use propylene glycol as an excipient have been seen in a number of people, particularly with large bolus dosages. Responses may include CNS depression, "hypotension, bradycardia, QRS and T abnormalities on the ECG, arrhythmia, cardiac arrhythmias, seizures, agitation, serum hyperosmolality, lactic acidosis, and haemolysis". 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 its glucuronide-form. The speed of renal filtration decreases as dosage increases, which may be due to propylene glycol's mild anesthetic / CNS-depressant properties as an alcohol. In one case, intravenous administration of propylene glycol-suspended nitroglycerin to an elderly man may have induced coma and acidosis. However, no confirmed lethality from propylene glycol was reported.

Animals

Propylene glycol is an approved food additive for dog and sugar glider food under the category of animal feed and is generally recognized as safe for dogs, with an LD50 of 9 mL/kg. The LD50 is higher for most laboratory animals (20 mL/kg). However, it is prohibited for use in food for cats due to links to Heinz body formation and a reduced lifespan of red blood cells. Heinz body formation from MPG has not been observed in dogs, cattle, or humans.

Allergic reaction

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). The North American Contact Dermatitis Group (NACDG) data from 1996 to 2006 showed that the most common site for propylene glycol contact dermatitis was the face (25.9%), followed by a generalized or scattered pattern (23.7%). Investigators believe that the incidence of allergic contact dermatitis to propylene glycol may be greater than 2% in patients with eczema or fungal infections, which are very common in countries with lesser sun exposure and lower-than-normal vitamin D balances. Therefore, propylene glycol allergy is more common in those countries.

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's Allergen of the Year for 2018. 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. 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.

Environmental impacts

Propylene glycol occurs naturally, probably as the result of anaerobic catabolism of sugars in the human gut. It is degraded by vitamin B12-dependent enzymes, which convert it to propionaldehyde.

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, or adsorption to sediment. 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-h LC50 value of 40,613 mg/L in a study with Oncorhynchus mykiss. Similarly, the lethal concentration determined in marine fish is a 96-h LC50 of 10,000 mg/L in Scophthalmus maximus.

Although propylene glycol has low toxicity, it exerts high levels of biochemical 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 of dissolved oxygen (DO) in the water column are consumed when microbial populations decompose propylene glycol.

References

References

1. (1989). "The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals". Merck & Co.
2. "Propylene Glycol_msds".
3. Zaripov, Z.I.. (1982). "Experimental study of the isobaric heat capacity of liquid organic compounds with molecular weights of up to 4000 a.e.m.".
4. GHS: "Kein gefährlicher Stoff nach GHS" [https://gestis.dguv.de/data?name=013620 GESTIS 013620]
5. "Propylene Glycol - Cameo Chemicals". [[NOAA]].
6. Zapka, Maskrey. (2016). "Hawaii Energy and Environmental Technologies (HEET) Initiative".
7. (2018). "Propanediols".
8. (30 August 2024). "Propylene glycol, Subpart B - Listing of Specific Substances Affirmed as GRAS, Sec. 184.1666 (original 25 June 1982)". Title 21, Code of Federal Regulations, US Food and Drug Administration.
9. (1989). "Petrochemical Processes". Editions Technip.
10. "1,2-propanediol: chemical product info at CHEMINDUSTRY.RU".
11. (2020-07-20). "Propylene Glycol USP".
12. Hanessian, Stephen. (1983). "Total Synthesis of Natural Products: The 'Chiron' Approach". Pergamon press.
13. (31 July 2020). "Propylene glycol". Select Committee on GRAS Substances, US Food and Drug Administration.
14. (29 October 2024). "Propylene glycol: Substances added to food". US Food and Drug Administration.
15. EFSA Panel on Food Additives and Nutrient Sources added to Food. (2018). "Re-evaluation of propane-1,2-diol (E 1520)as a food additive". EFSA Journal.
16. (13 February 2013). "Modification to the List of permitted emulsifying, gelling, stabilizing or thickening agents to enable the use of propylene glycol mono fatty acid esters as an emulsifier and stabilizer in ice milk mix". Health Canada, Government of Canada.
17. (18 May 2021). "What Is Propylene Glycol, and What Does It Do in Our Food?". Food Insight.
18. G. Jackson, R. T. Roberts and T. Wainwright. (January 1980). "Mechanism of Beer Foam Stabilization by Propylene Glycol Alginate". Journal of the Institute of Brewing.
19. (August 1991). "Propylene glycol (PIM 443)". IPCS INChem.
20. (2016). "Over the counter (OTC) artificial tear drops for dry eye syndrome". Cochrane Database Syst Rev.
21. (April 2012). "Technical Development Document for the Final Effluent Limitations Guidelines and New Source Performance Standards for the Airport Deicing Category". U.S. Environmental Protection Agency (EPA).
22. (2012-06-11). "5 Ways to Winterize a Vacant Home". wikiHow.
23. "Properties of Some Particular Solutions". Portal del DMT.
24. Salnick, Robert. (2010-08-04). "Windborne in Puget Sound: Why does a holding plate work?". Windborneinpugetsound.blogspot.com.
25. "Material Safety Data Sheet: Winter Care RV Antifreeze". Chemical Specialties.
26. (2021-01-01). "Association between electronic cigarette use and fragility fractures among US adults". American Journal of Medicine Open.
27. Varlet, Vincent. (2015). "Toxicity Assessment of Refill Liquids for Electronic Cigarettes". International Journal of Environmental Research and Public Health.
28. (2015). "Predicting Abraham model solvent coefficients". Chemistry Central Journal.
29. Nielsen, Nicolaj. (2004). "Propylene glycol for dairy cows". Animal Feed Science and Technology.
30. (September 2012). "Safety assessment of propylene glycol, tripropylene glycol, and PPGs as used in cosmetics". International Journal of Toxicology.
31. (2013-03-13). "DNA preservation: a test of commonly used preservatives for insects". Invertebrate Systematics.
32. Nevada Film Office. (February 19, 2019). "Production Notes: Haze Machines".
33. Daniel, Brea. (July 15, 2016). "Atmosphere: Hazers, Fazers, Smoke and Fog 101 by Daniel Brea".
34. "Safety Data Sheet: Martin Effect Fluids, Pg. 3".
35. "What Is a Couplant?".
36. National Toxicology Program NIEHS. (2004). "NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Propylene Glycol".
37. CDC. (March 11, 2019). "Electronic Cigarettes". Centers for Disease Control and Prevention.
38. Havelka, Jacqueline. (April 27, 2017). "Is Vaping Safe?".
39. Peki, Winston. (May 5, 2019). "Are Vaporizers Safe?".
40. (2020). "Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products". [[Centers for Disease Control and Prevention]].
41. Lehman A, Newman H. (1937). "Propylene glycol: Rate of metabolism absorption, and excretion, with a method for estimation in body fluids.". J Pharmacol Exp Ther.
42. Hamilton, D. J.. (1890). "Gastric Dyspepsia". The Lancet.
43. (2010). "Material Safety Data Sheet Propionaldehyde MSDS". ScienceLab.com.
44. Miller DN, Bazzano G. (1965). "Propanediol metabolism and its relation to lactic acid metabolism". Ann NY Acad Sci.
45. Ruddick JA. (1972). "Toxicology, metabolism, and biochemistry of 1,2-propanediol". Toxicol Appl Pharmacol.
46. "Lethal dose table".
47. Alton E. Martin and Frank H. Murphy. "GLYCOLS - PROPYLENE GLYCOLS". Dow Chemical Company.
48. Flanagan RJ; Braithwaite RA; Brown SS; et al. The International Programme on Chemical Safety: Basic Analytical Toxicology. WHO, 1995.
49. (29 September 2015). "Select Committee on GRAS Substances Opinion: Propylene Glycol and Propylene Glycol Monostearate". Select Committee on GRAS Substances, US Food and Drug Administration.
50. (1972). "Long-term toxicity of propylene glycol in rats". [[Food and Cosmetics Toxicology]].
51. (2008). "Addendum to the Toxicological Profile for Propylene Glycol". Agency for Toxic Substances and Disease Registry.
52. (January 23–26, 2001). "1,2-Dihydroxypropane: SIDS Initial Assessment Report for 11th SIAM". UNEP Publications.
53. (1999). "Propylene glycol". Title 21, U.S. Code of Federal Regulations.
54. (September 1947). "Tests for the chronic toxicity of propylene glycol and triethylene glycol on monkeys and rats by vapor inhalation and oral administration". Journal of Pharmacology and Experimental Therapeutics.
55. [http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_091b/0901b8038091b508.pdf?filepath=propyleneglycol/pdfs/noreg/117-01682.pdf A Guide to Glycols], Dow, page 36
56. (29 June 2020). "Vaping vs Smoking: Is the Former Really a Healthier Alternative?".
57. (Oct 19, 2010). "Everyday Substances Increase Risk of Allergies in Children, Swedish Study Reveals". ScienceDaily.
58. "Chemical Compounds Emitted From Common Household Paints and Cleaners Increase Risks of Asthma and Allergies in Children". Harvard.
59. Choi, Hyunok. (2010-10-18). "Common Household Chemicals and the Allergy Risks in Pre-School Age Children". PLOS ONE.
60. Ruddick. (1972). "Toxicology, metabolism, and biochemistry of 1,2-propanediol.". Toxicol Appl Pharmacol.
61. Szajewski, Janusz. "Propylene Glycol (PIM 443)." 1991. 2 June 2010 http://www.inchem.org/documents/pims/chemical/pim443.htm#SectionTitle:9.1%20%20Acute%20poisoning
62. (1987). "Propylene Glycol Pharmacokinetics and Effects after Intravenous Infusion in Humans". Therapeutic Drug Monitoring.
63. (1932). "The general properties, actions, and toxicity of propylene glycol". [[Journal of Pharmacology and Experimental Therapeutics.
64. (1984). "Propylene glycol intoxication due to intravenous nitroglycerin". The Lancet.
65. FDA. "Subchapter E - Animal Drugs, Feeds, and Related Products; § 582.1666. Propylene glycol." ''Code of Federal Regulations,'' {{USCFR. 21. 582. 1666
66. (2006). "Small animal toxicology". Saunders Elsevier.
67. "Propylene glycol and cats".
68. (January 2009). "Positive patch-test reactions to propylene glycol: a retrospective cross-sectional analysis from the North American Contact Dermatitis Group, 1996 to 2006". Dermatitis: Contact, Atopic, Occupational, Drug.
69. (November 2005). "Skin-sensitizing and irritant properties of propylene glycol". Contact Dermatitis.
70. (November 2010). "Results of patch testing to personal care product allergens in a standard series and a supplemental cosmetic series: an analysis of 945 patients from the Mayo Clinic Contact Dermatitis Group, 2000-2007". Journal of the American Academy of Dermatology.
71. (1994). "AMA Drug Evaluations Annual 1994". American Medical Association, Council on Drugs.
72. (January–February 2018). "Propylene Glycol". Dermatitis: Contact, Atopic, Occupational, Drug.
73. "Allergen of the year may be nearer than you think".
74. (2018). "Patch Testing to Propylene Glycol: The Mayo Clinic Experience.". Dermatitis.
75. (2003). "PduP is a coenzyme-a-acylating propionaldehyde dehydrogenase associated with the polyhedral bodies involved in B₁₂ -dependent 1,2-propanediol degradation by ''Salmonella enterica'' serovar Typhimurium LT2". Archives of Microbiology.
76. (April 2012). "Environmental Impact and Benefit Assessment for the Final Effluent Limitation Guidelines and Standards for the Airport Deicing Category". U.S. Environmental Protection Agency (EPA).