Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Propylene glycol: Difference between pages

{{Distinguish|Polypropylene glycol|Ethylene glycol|Polyethylene glycol}}

{{about|1,2-propanediol|other propylene glycols|Propanediol}}

| Watchedfields = changed

| verifiedrevid = 477004593

| Reference = <ref>{{cite book |url= https://archive.org/details/merckindexency00buda |title= The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals |publisher= Merck & Co |isbn= 978-0911910285 |year= 1989 |url-access= registration }}</ref>

| Name =

| ImageFile = Propylene glycol chemical structure.png

| ImageName = Propylene glycol

| ImageFileR1 = PropyleneGlycol-spaceFill.png

| ImageNameR1 = Space-filling model

| ImageFileL1 = PropyleneGlycol-stickAndBall.png

| ImageNameL1 = ball-and-stick model

| PIN = Propane-1,2-diol

| SystematicName =

| OtherNames = {{Unbulleted list|Propylene glycol|α-Propylene glycol|1,2-Propanediol|1,2-Dihydroxypropane|Methyl ethyl glycol|Methylethylene glycol}}

| IUPACName =

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII1_Ref = {{fdacite|correct|FDA}}

| UNII1 = 942194N4TD

| UNII1_Comment = (S-enantiomer)

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo_Comment = racemic

| CASNo2 = 4254-15-3

| CASNo2_Comment = S-enantiomer

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| KEGG = C00583

| EC_number = 200-338-0

| SMILES = CC(O)CO

| RTECS = TY6300000

| C=3 | H=8 | O=2

| Appearance = colourless liquid

| Odor = odorless

| Density = 1.036 g/cm³

| MeltingPtC = -59

| Solubility = [[Miscible]]

| Solubility1 = Miscible

| Solvent1 = ethanol

| Solubility2 = Miscible

| Solvent2 = diethyl ether

| Solubility3 = Miscible

| Solvent3 = acetone

| Solubility4 = Miscible

| Solvent4 = chloroform

| BoilingPtC = 188.2

| ThermalConductivity = 0.34 W/m·K (50% H₂O @ {{convert|90|°C|°F}})

| VaporPressure = 10.66 Pa (20 °C)

| Viscosity = 0.042 Pa·s

| LogP = -1.34<ref name="chemsrc">{{Cite web |url= https://www.chemsrc.com/en/cas/57-55-6_674628.html |title= Propylene Glycol_msds}}</ref>

| Section3 =

| Section4 = {{Chembox Thermochemistry

| DeltaHf =

| DeltaHc =

| Entropy =

| HeatCapacity = 189.9 J/(mol·K) <ref>{{cite book |last=Zaripov |first=Z.I. |author-link= |date=1982 |title=Experimental study of the isobaric heat capacity of liquid organic compounds with molecular weights of up to 4000 a.e.m. |url=https://webbook.nist.gov/cgi/cbook.cgi?ID=C57556&Mask=1883#ref-5 |location= |publisher= |page= |isbn=}}</ref>

}} <!--Chembox Thermochemistry-->

| Section5 =

| Section6 = {{Chembox Pharmacology

| ATCvet = yes

| ATCCode_prefix = A16

| ATCCode_suffix = QA01

}}

| ExternalSDS =

| NFPA-H = 0

| NFPA-F = 1

| NFPA-R = 0

| NFPA-S =

| GHSPictograms =

| GHSSignalWord =

| HPhrases = {{HPhrases|}}

| PPhrases = {{PPhrases|}}

| GHS_ref = <ref>GHS: "Kein gefährlicher Stoff nach GHS" [https://gestis.dguv.de/data?name=013620 GESTIS 013620]</ref>

}}<ref>{{cite web|url=http://cameochemicals.noaa.gov/chemical/9030|title=Propylene Glycol - Cameo Chemicals|website=NOAA Office of Response and Restoration|publisher=[[NOAA]]|access-date=3 October 2018}}</ref>

| OtherFunction_label = [[glycol]]s

| OtherFunction = [[Ethylene glycol]], [[1,3-propanediol]]

'''Propylene glycol''' ([[IUPAC nomenclature|IUPAC name]]: '''propane-1,2-diol''') is a viscous, colorless liquid. It is almost odorless and has a faintly sweet taste. Its [[chemical formula]] is CH₃CH(OH)CH₂OH.

As it contains two [[Alcohol (chemistry)|alcohol]] groups, it is classed as a [[diol]]. An [[aliphatic]] diol may also be called a [[glycol]]. It is [[miscible]] with a broad range of solvents, including [[water]], [[acetone]], and [[chloroform]]. In general, glycols<ref>{{Cite book |last=Zapka |first=Maskrey |title=Hawaii Energy and Environmental Technologies (HEET) Initiative |year=2016}}</ref> are non-irritating and have very low [[Volatility (chemistry)|volatility]].<ref name=Ullmann>{{Ullmann|title=Propanediols|first1=Carl J. |last1=Sullivan|first2=Anja|last2=Kuenz|first3=Klaus-Dieter|last3=Vorlop|year=2018|doi=10.1002/14356007.a22_163.pub2}}</ref>

It is produced on a large scale primarily for the production of [[polymer]]s. In the European Union, it has [[E-number]] E1520 for food applications. For cosmetics and [[pharmacology]], the number is E490. Propylene glycol is also present in [[propylene glycol alginate]], which is known as E405. Propylene glycol is a compound which is [[Generally recognized as safe|GRAS]] (generally recognized as safe) by the US [[Food and Drug Administration]] under 21 CFR x184.1666, and is also approved by the FDA for certain uses as an indirect food additive. Propylene glycol is approved and used as a vehicle for topical, oral, and some intravenous pharmaceutical preparations in the U.S. and in Europe.

==Structure==

The compound is sometimes called (alpha) '''α-propylene glycol''' to distinguish it from the [[isomer]] [[1,3-Propanediol|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.<ref name=Ullmann/> Manufacturers use either non-catalytic high-temperature process at {{convert|200|C|0}} to {{convert|220|C|0}}, or a catalytic method, which proceeds at {{convert|150|C|0}} to {{convert|180|C|0}} in the presence of ion exchange resin or a small amount of sulfuric acid or alkali.<ref name=petro>{{Cite book |author1=Chauvel, Alain |author2=Lefebvre, Gilles | title=Petrochemical Processes | volume = 2: Major Oxygenated, Chlorinated and Nitrated Derivatives | publisher=Editions Technip | isbn= 9782710805632 | page=26|year=1989 }}</ref>

[[File:1,2-Propandiol Synthesis V1.svg|300px|center]]

Final products contain 20% propylene glycol, 1.5% of [[dipropylene glycol]], and small amounts of other [[polypropylene glycol]]s.<ref>{{cite web|url=http://chemindustry.ru/1,2-Propanediol.php|title=1,2-propanediol: chemical product info at CHEMINDUSTRY.RU<!-- Bot generated title -->|access-date=3 October 2018}}</ref> 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.<ref>{{Cite web|date=2020-07-20|title=Propylene Glycol USP|url=https://berrymanchemical.com/blog/propylene-glycol-usp/|access-date=2020-07-28|website=Berryman Chemical|language=en-GB|archive-date=2020-07-28|archive-url=https://web.archive.org/web/20200728212012/https://berrymanchemical.com/blog/propylene-glycol-usp/|url-status=dead}}</ref>

Propylene glycol can also be obtained from [[glycerol]], a byproduct from the production of [[biodiesel]].<ref name=Ullmann/> 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|1,2-propanediol]]. Three-carbon [[deoxysugar]]s are also precursor to the 1,2-diol.<ref name=Ullmann/>

A small-scale, nonbiological route from [[Mannitol|<small>D</small>-mannitol]] is illustrated in the following scheme:<ref>{{cite book|last=Hanessian|first=Stephen|title=Total Synthesis of Natural Products: The 'Chiron' Approach|year=1983|publisher=Pergamon press|isbn=978-0080307152|page=41}}</ref>

[[File:(s)-Propanediol from D-Mannitol.png|480px|center]]

==Applications==

===Polymers===

Forty-five percent of propylene glycol produced is used as a chemical feedstock for the production of unsaturated [[polyester resin]]s. 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 [[cross-link|crosslink]]ing to yield [[thermoset plastic]]s. Related to this application, propylene glycol reacts with propylene oxide to give [[oligomers]] and polymers that are used to produce [[polyurethane]]s.<ref name=Ullmann/> 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===

Propylene glycol is also used in various edible items such as coffee-based drinks, [[Sweeteners|liquid sweeteners]], ice cream, whipped dairy products and soda.<ref>{{cite web | url=https://www.forbes.com/sites/trevorbutterworth/2014/06/16/quackmail-why-you-shouldnt-fall-for-the-internets-newest-fool-the-food-babe/ | title=Quackmail: Why You Shouldn't Fall For The Internet's Newest Fool, The Food Babe. | publisher=Forbes | work=Butterworth, Trevor | date=16 June 2014 | access-date=18 March 2015}}</ref><ref>{{cite journal |title=Mechanism of Beer Foam Stabilization by Propylene Glycol Alginate | author=G. Jackson, R. T. Roberts and T. Wainwright |journal=Journal of the Institute of Brewing |date=January 1980 | volume=86 | issue=1 | pages=34–37 | doi=10.1002/j.2050-0416.1980.tb03953.x}}</ref> [[Vaporizer (inhalation device)|Vaporizer]]s used for delivery of pharmaceuticals or personal-care products often include propylene glycol among the ingredients.<ref name=Ullmann/> In alcohol-based hand sanitizers, it is used as a humectant to prevent the skin from drying.<ref>{{Cite news|url=https://www.livestrong.com/article/164674-ingredients-in-hand-sanitizer/|title=Ingredients in Hand Sanitizer|last=Lohrey|first=Jackie|work=LIVESTRONG.COM|access-date=2018-06-11}}</ref> Propylene glycol is used as a [[solvent]] in many [[pharmaceuticals]], including [[oral administration|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.<ref>{{cite web | url=http://www.inchem.org/documents/pims/chemical/pim443.htm | title=Propylene glycol (PIM 443) | publisher=IPCS INChem | date=August 1991 | access-date=July 2, 2009 | vauthors = ((Janusz Szajewski, MD, Warsaw Poison Control Centre))}}</ref> Propylene glycol is also used as a solvent and carrier for many pharmaceutical [[Capsule (pharmacy)|capsule]] preparations. Additionally, certain formulations of [[artificial tears]] use propylene glycol as an ingredient.<ref>{{cite journal |vauthors=Pucker AD, Ng SM, Nichols JJ |title= Over the counter (OTC) artificial tear drops for dry eye syndrome |journal=Cochrane Database Syst Rev|volume=2016 |pages= CD009729 |date=2016 |issue= 2 |pmid= 26905373 |doi= 10.1002/14651858.CD009729.pub2 |pmc=5045033}}</ref>

[[File:Deicing a 737 (8407234815).jpg|thumb|Propylene glycol is commonly used to [[de-ice]] aircraft.]]

===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.<ref name=Ullmann/><ref>{{cite web |url=http://pubs.acs.org/cen/whatstuff/stuff/7901scit5.html |title=What's That Stuff? Aircraft Deicers |website=Chemical & Engineering News |publisher=American Chemical Society |date=2000-07-10 |access-date=2013-06-21}}</ref> Water-propylene glycol mixtures dyed pink to indicate the mixture is relatively nontoxic are sold under the name of [[Recreational vehicle|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.<ref>{{cite web|url=http://www.wikihow.com/Winterize-a-Vacant-Home |title=5 Ways to Winterize a Vacant Home |publisher=wikiHow |date=2012-06-11 |access-date=2014-02-27}}</ref> The [[eutectic composition]]/temperature is 60:40 propylene glycol:water/−60&nbsp;°C.<ref>{{cite web|url=http://webserver.dmt.upm.es/~isidoro/bk3/c07sol/Solution%20properties.pdf |title=Properties of Some Particular Solutions |publisher=Portal del DMT |access-date=2014-02-27}}</ref><ref>{{cite web|last=Salnick |first=Robert |url=http://windborneinpugetsound.blogspot.com/2010/08/why-does-holding-plate-work.html |title=Windborne in Puget Sound: Why does a holding plate work? |publisher=Windborneinpugetsound.blogspot.com |date=2010-08-04 |access-date=2014-02-27}}</ref> The −50&nbsp;°F/−45&nbsp;°C commercial product is, however, water rich; a typical formulation is 40:60.<ref>{{cite web|url=http://www.chemicalspec.com/Winter_Care_4060_RV_Antifreeze.pdf |title=Material Safety Data Sheet: Winter Care RV Antifreeze |publisher=Chemical Specialties |access-date=2014-02-27}}</ref>

===Electronic cigarettes liquid===

Propylene glycol, vegetable [[glycerin]],<ref>{{Cite journal |last1=Agoons |first1=Dayawa D. |last2=Agoons |first2=Batakeh B. |last3=Emmanuel |first3=Kelechi E. |last4=Matawalle |first4=Firdausi A. |last5=Cunningham |first5=Jessica M. |date=2021-01-01 |title=Association between electronic cigarette use and fragility fractures among US adults |journal=American Journal of Medicine Open |language=en |volume=1-6 |pages=100002 |doi=10.1016/j.ajmo.2021.100002 |s2cid=244502249 |issn=2667-0364|doi-access=free |pmid=39036626 |pmc=11256257 }}</ref> or a mixture of both, are the main ingredients in [[e-liquid]] used in [[electronic cigarettes]]. They are [[Aerosolization|aerosolized]] to resemble smoke and serve as carriers for substances such as [[nicotine]] and [[flavorant]]s.<ref name="Varlet">{{cite journal | last=Varlet | first=Vincent | display-authors=etal | title=Toxicity Assessment of Refill Liquids for Electronic Cigarettes | journal=International Journal of Environmental Research and Public Health | volume=12 | issue=5 | date=2015 | pages=4796–4815 | issn=1660-4601 | doi=10.3390/ijerph120504796 | pmid=25941845 | pmc=4454939 | doi-access=free }}</ref>

==Miscellaneous applications<!--if 2 million tons are produced annually, a lot of minor apps-->==

* As a [[solvent]] for many substances, both natural and synthetic.<ref name="BradleyAbraham2015">{{cite journal|last1=Bradley|first1=Jean-Claude|last2=Abraham|first2=Michael H|last3=Acree|first3=William E|last4=Lang|first4=Andrew|title=Predicting Abraham model solvent coefficients|journal=Chemistry Central Journal|volume=9|issue=1|year=2015|pages=12|issn=1752-153X|doi=10.1186/s13065-015-0085-4|pmid=25798192|pmc=4369285 |doi-access=free }}</ref>

* As a [[humectant]] (E1520).

* As a [[Freezing-point depression|freezing point depressant]] for [[slurry ice]].

* In veterinary medicine as an oral treatment for [[hyperketonaemia]] in [[ruminant]]s.<ref>{{cite journal | url=https://www.researchgate.net/publication/248332819 | title=Propylene glycol for dairy cows | author=Nielsen, Nicolaj | journal=Animal Feed Science and Technology | doi=10.1016/j.anifeedsci.2004.03.008 | volume=115 | issue=3–4 | pages=191–213| year=2004 }}</ref>

* In the cosmetics industry, where propylene glycol is very commonly used as a carrier or base for various types of makeup.<ref>{{Cite journal|last1=Fiume|first1=Monice M.|last2=Bergfeld|first2=Wilma F.|last3=Belsito|first3=Donald V.|last4=Hill|first4=Ronald A.|last5=Klaassen|first5=Curtis D.|last6=Liebler|first6=Daniel|last7=Marks|first7=James G.|last8=Shank|first8=Ronald C.|last9=Slaga|first9=Thomas J.|display-authors=3|date=September 2012|title=Safety assessment of propylene glycol, tripropylene glycol, and PPGs as used in cosmetics|journal=International Journal of Toxicology|volume=31|issue=5 Suppl|pages=245S–60S|doi=10.1177/1091581812461381|issn=1092-874X|pmid=23064775|s2cid=24754435|doi-access=free}}</ref>

* For [[pitfall trap|trapping]] and preserving insects (including as a [[DNA]] preservative).<ref>{{Cite journal|last1=Rubin|first1=Benjamin E. R.|last2=Czekanski-Moir|first2=Jesse E.|last3=Wray|first3=Brian D.|last4=Moreau|first4=Corrie S.|date=2013-03-13|title=DNA preservation: a test of commonly used preservatives for insects|journal=Invertebrate Systematics|language=en|volume=27|issue=1|pages=81–86|doi=10.1071/IS12067|s2cid=4820463|issn=1447-2600}}</ref>

* For the creation of [[theatrical smoke and fog]] in special effects for film and live entertainment. So-called 'smoke machines' or 'hazers' vaporize 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. 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 vapor. The vapor 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.<ref>{{Cite web|url=https://nevadafilm.com/production-notes-haze-machines/|title=Production Notes: Haze Machines|last=Nevada Film Office|date=February 19, 2019|website=nevadafilm.com|access-date=November 1, 2019}}</ref><ref>{{Cite web|url=https://www.provideocoalition.com/atmosphere101|title=Atmosphere: Hazers, Fazers, Smoke and Fog 101 by Daniel Brea|last=Daniel|first=Brea|date=July 15, 2016|website=provideocoalition.com|url-status=dead|archive-url=https://web.archive.org/web/20160719141901/http://www.provideocoalition.com/atmosphere101|archive-date=2016-07-19|access-date=November 1, 2019}}</ref>

* As an additive in [[polymerase chain reaction]] (PCR) to reduce the melting temperature of [[Nucleic acid|nucleic acids]] for targeting of [[GC rich]] sequences.{{Citation needed|date=April 2021}}

* 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.

==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.<ref name="National Toxicology Program NIEHS 2004">{{citation |author= National Toxicology Program NIEHS |year= 2004|title=NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Propylene Glycol | id = NIH Publication No. 04-4482 }}</ref> The [[safety of electronic cigarettes]]—which utilize propylene glycol-based preparations of nicotine or THC and other cannabinoids—is the subject of much controversy.<ref>{{Cite web|url=https://www.cdc.gov/tobacco/basic_information/e-cigarettes/index.htm|title=Electronic Cigarettes|last=CDC|date=March 11, 2019}}</ref><ref>{{Cite web|url=https://www.leafly.com/news/health/vaping-vs-smoking-marijuana-safety|title=Is Vaping Safe?|last=Havelka|first=Jacqueline|date=April 27, 2017|website=leafly.com}}</ref><ref>{{Cite web|url=https://www.herbonaut.com/are-vaporizers-safe/|title=Are Vaporizers Safe?|last=Peki|first=Winston|date=May 5, 2019|website=herbonaut.com}}</ref> [[Tocopheryl acetate|Vitamin E acetate]] has also been identified in this controversy.<ref>{{cite web|url=https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#overview|title=Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products|publisher=[[Centers for Disease Control and Prevention]]|year=2020}}</ref>

===Oral administration===

The acute oral toxicity of propylene glycol is very low, and large quantities are required to cause perceptible health effects in humans; in fact, the toxicity of propylene glycol is one third that of [[ethanol]].<ref>{{cite journal |title=Propylene glycol: Rate of metabolism absorption, and excretion, with a method for estimation in body fluids. |author=Lehman A, Newman H |journal=J Pharmacol Exp Ther |volume=60 |pages=312–322 |year=1937 }}</ref> 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),<ref>{{cite journal |author = Hamilton, D. J. |title = Gastric Dyspepsia |journal = The Lancet |volume =2 |issue = 3493 |year = 1890 |page = 306 |doi=10.1016/S0140-6736(02)17110-8}}</ref> and [[propionaldehyde]] (a potentially hazardous substance).<ref>{{cite web |url = http://www.sciencelab.com/msds.php?msdsId=9924730 |publisher = ScienceLab.com |year = 2010 |title = Material Safety Data Sheet Propionaldehyde MSDS}}</ref><ref>{{cite journal |author = Miller DN, Bazzano G |year = 1965 |title = Propanediol metabolism and its relation to lactic acid metabolism |journal = Ann NY Acad Sci |volume = 119 |pages = 957–973 |bibcode = 1965NYASA.119..957M |last2 = Bazzano |doi = 10.1111/j.1749-6632.1965.tb47455.x |pmid = 4285478 |issue = 3| s2cid = 37769342 }}</ref><ref>{{cite journal |author = Ruddick JA |year = 1972 |title = Toxicology, metabolism, and biochemistry of 1,2-propanediol |journal = Toxicol Appl Pharmacol |volume = 21 |issue = 1 |pages = 102–111 |doi = 10.1016/0041-008X(72)90032-4 |pmid = 4553872 |bibcode = 1972ToxAP..21..102R }}</ref> According to the [[Dow Chemical Company]], the [[Median lethal dose|LD₅₀]] (dose that kills 50% of the test population) for rats is 20 g/kg (oral/rat).<ref>{{cite web | website = rocklinusd.org|title= Lethal dose table |url= http://whs.rocklinusd.org/documents/Science/Lethal_Dose_Table.pdf}}</ref><ref>{{cite web |author= Alton E. Martin and Frank H. Murphy | publisher = Dow Chemical Company |title= GLYCOLS - PROPYLENE GLYCOLS |url= http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_006e/0901b8038006e13c.pdf?filepath=propyleneglycol/pdfs/noreg/117-01785.pdf&fromPage=GetDoc }}</ref>

Toxicity generally occurs at plasma concentrations over 4&nbsp;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 dose|bolus doses]].<ref>Flanagan RJ; Braithwaite RA; Brown SS; et al. The International Programme on Chemical Safety: Basic Analytical Toxicology. WHO, 1995.</ref> It would be nearly impossible to reach toxic levels by consuming foods or supplements, which contain at most 1&nbsp;g/kg of PG, except for alcoholic beverages in the US which are allowed 5 percent = 50&nbsp;g/kg.<ref name="FDA-PG">U.S. Food and Drug Administration (FDA). "Subchapter B - Food for Human Consumption. § 184.1666. Propylene glycol." ''Code of Federal Regulations,'' {{USCFR|21|184|1666}}</ref> Cases of propylene glycol poisoning are usually related to either inappropriate intravenous administration or accidental ingestion of large quantities by children.<ref>National Library of Medicine; Propylene glycol is used in antifreeze. Human Toxicity Excerpts: CAS Registry Number: 57-55-6 (1,2-Propylene Glycol). Selected toxicity information from HSDB. 2005.</ref>

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&nbsp;mg/kg bw/day. No effects on fertility were seen in either the first or second generation of treated mice.<ref name="National Toxicology Program NIEHS 2004"/> In a 2-year study, 12 rats were provided with feed containing as much as 5% propylene glycol, and showed no apparent ill effects.<ref>{{cite journal |last1=Gaunt |first1=I. F. |last2=Carpanini |first2=F. M. B. |last3=Grasso |first3=P. |last4=Lansdown |first4=A. B. G. |title=Long-term toxicity of propylene glycol in rats |journal=[[Food and Cosmetics Toxicology]] |year=1972 |volume=10 |issue=2 |pages=151–162 |doi=10.1016/S0015-6264(72)80193-7 |pmid=5072816 }}</ref> Because of its low chronic oral toxicity, propylene glycol was classified by the U.S. [[Food and Drug Administration]] as "[[generally recognized as safe]]" (GRAS) for use as a direct [[food additive]], including frozen foods such as [[ice cream]] and [[frozen dessert]]s.<ref name="FDA-PG"/><ref>{{cite web |url=http://www.accessdata.fda.gov/scripts/fcn/fcnDetailNavigation.cfm?rpt=scogslisting&id=262 |title=Database of Select Committee on GRAS Substances (SCOGS) Reviews |publisher=FDA |access-date=2016-05-11}}</ref> The GRAS designation is specific to its use in food, and does not apply to other uses.<ref>FDA. "Subchapter B - Food for Human Consumption. § 182.1. Substances that are generally recognized as safe." ''Code of Federal Regulations,'' {{USCFR|21|182|1}}</ref>

===Skin and eye contact===

[[File:E-Cigarette-Electronic Cigarette-E-Cigs-E-Liquid-Vaping-Cloud Chasing (16348040092).jpg|thumb|Propylene glycol is often used in [[electronic cigarettes]].]]

Propylene glycol may be non-irritating to the skin, see section [[#Allergic reaction|Allergic reaction]] below for details on allergic reactions.<ref>{{citation | publisher = Agency for Toxic Substances and Disease Registry |year= 2008|title=Addendum to the Toxicological Profile for Propylene Glycol |page= 7 }}</ref> Undiluted propylene glycol is minimally irritating to the eye, producing slight transient [[conjunctivitis]]; 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&nbsp;mg/m3 and 30 minutes exposures to concentrations of up to 871&nbsp;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.<ref name="Dalton 2018">{{cite journal | title=Lack of respiratory and ocular effects following acute propylene glycol exposure in healthy humans. | author1=Dalton P |author2=Soreth B |author3=Maute C |author4=Novaleski C |author5=Banton M |display-authors=3| journal=Inhal. Toxicol. | volume=30 | issue=3 | pages=124–132| year=2018| doi=10.1080/08958378.2018.1470207 | pmid=29764241 | bibcode=2018InhTx..30..124D | s2cid=21711274 }}</ref>

Propylene glycol has not caused [[sensitization]] or carcinogenicity in laboratory animal studies, nor has it demonstrated [[Genotoxicity|genotoxic]] potential.<ref name="UNEP">1,2-Dihydroxypropane SIDS Initial Assessment Profile <{{cite web |url=http://www.chem.unep.ch/irptc/sids/OECDSIDS/57-55-6.pdf |title=Archived copy |access-date=2008-01-08 |url-status=dead |archive-url=https://web.archive.org/web/20090219045910/http://www.chem.unep.ch/irptc/sids/OECDSIDS/57-55-6.pdf |archive-date=2009-02-19 }}>, UNEP Publications, SIAM 11, U.S.A, January 23–26, 2001, page 21.</ref><ref>Title 21, U.S. Code of Federal Regulations. 1999.</ref>

===Inhalation===

Inhalation of propylene glycol vapors appears to present no significant hazard in ordinary applications.<ref name="Robertson47">{{cite journal | url=http://jpet.aspetjournals.org/content/91/1/52.abstract | title=Tests for the chronic toxicity of propylene glycol and triethylene glycol on monkeys and rats by vapor inhalation and oral administration |author1=Robertson, OH |author2=Loosli, CG |author3=Puck, TT |author4=Wise, H |author5=Lemon, HM |author6=Lester, W |display-authors=3| journal=Journal of Pharmacology and Experimental Therapeutics|date=September 1947 | volume=91 | issue=1 | pages=52–76 | pmid=20265820 | quote=air containing these vapors in amounts up to the saturation point is completely harmless}}</ref> 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.<ref>[http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_091b/0901b8038091b508.pdf?filepath=propyleneglycol/pdfs/noreg/117-01682.pdf A Guide to Glycols], Dow, page 36</ref> 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.<ref>{{Cite web|url=https://vapingcheap.com/vaping-vs-smoking/#tab-con-1|title = Vaping vs Smoking: Is the Former Really a Healthier Alternative?|date = 29 June 2020}}</ref>

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.<ref>{{cite news |url=https://www.sciencedaily.com/releases/2010/10/101019084607.htm |title=Everyday Substances Increase Risk of Allergies in Children, Swedish Study Reveals |work=ScienceDaily |date=Oct 19, 2010 }}</ref><ref>{{cite web|url=http://www.hsph.harvard.edu/news/features/features/paints-cleaners-children-asthma-allergy.html|title=Chemical Compounds Emitted From Common Household Paints and Cleaners Increase Risks of Asthma and Allergies in Children|publisher=Harvard|access-date=3 October 2018|archive-date=17 February 2011|archive-url=https://web.archive.org/web/20110217071525/http://www.hsph.harvard.edu/news/features/features/paints-cleaners-children-asthma-allergy.html|url-status=dead}}</ref><ref>{{Cite journal| volume = 5| issue = 10| pmc = 2956675| pages = e13423| last = Choi| pmid = 20976153| first = Hyunok |author2=Norbert Schmidbauer |author3=[[Jan Sundell]] |author4=Mikael Hasselgren |author5=John Spengler |author6=Carl-Gustaf Bornehag| title = Common Household Chemicals and the Allergy Risks in Pre-School Age Children| journal = PLOS ONE| date = 2010-10-18| editor1-last = Hartl| editor1-first = Dominik| doi = 10.1371/journal.pone.0013423| bibcode = 2010PLoSO...513423C |display-authors=3| doi-access = free}}</ref>

===Intravenous administration===

Studies with intravenously administered propylene glycol have resulted in LD₅₀ values in rats and rabbits of 7&nbsp;mL/kg BW.<ref>{{Cite journal |author=Ruddick |year= 1972 |title=Toxicology, metabolism, and biochemistry of 1,2-propanediol. |journal=Toxicol Appl Pharmacol |volume=21 |issue= 1 |pages=102–111 |doi= 10.1016/0041-008X(72)90032-4 |pmid= 4553872|bibcode= 1972ToxAP..21..102R }}</ref> Ruddick (1972) also summarized intramuscular LD₅₀ data for rat as 13–20 mL/kg BW, and 6&nbsp;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 wave|T]] abnormalities on the ECG, [[Heart arrhythmia|arrhythmia]], cardiac arrhythmias, seizures, agitation, serum [[hyperosmolality]], [[lactic acidosis]], and [[haemolysis]]".<ref>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</ref> 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,<ref>{{Cite journal |last1 = Speth |first1 = P. A. J. |last2 = Vree |first2 = T. B. |last3 = Neilen |first3 = N. F. M. |last4 = De Mulder |first4 = P. H. M. |last5 = Newell |first5 = D. R. | last6 = Gore | first6 = M. E. |last7 = De Pauw |first7 = B. E. |doi = 10.1097/00007691-198709000-00001 |title = Propylene Glycol Pharmacokinetics and Effects after Intravenous Infusion in Humans |journal = Therapeutic Drug Monitoring |volume = 9 |issue = 3 |pages = 255–258 |year = 1987 |pmid = 3672566 |s2cid = 23317790 |display-authors=3 }}</ref> which may be due to propylene glycol's mild anesthetic / [[Cns depressants|CNS-depressant]] properties as an alcohol.<ref>{{cite journal |last1=Seidenfeld |first1=M. A. |last2=Hanzlik |first2=P. J. |year=1932 |title=The general properties, actions, and toxicity of propylene glycol |journal=[[Journal of Pharmacology and Experimental Therapeutics|J Pharmacol Exp Ther]] |volume=44 |pages=109–121 }}</ref> In one case, intravenous administration of propylene glycol-suspended [[Nitroglycerin (drug)|nitroglycerin]] to an elderly man may have induced coma and [[acidosis]].<ref name="DemeyDaelemans1984">{{cite journal |last1=Demey |first1=H. |last2=Daelemans |first2=R. |last3=De Broe |first3=M.E. |last4=Bossaert |first4=L. |title=Propylene glycol intoxication due to intravenous nitroglycerin |journal=The Lancet |volume=323 |issue=8390 |year=1984 |pages=1360 |issn=0140-6736 |doi=10.1016/S0140-6736(84)91860-9 |pmid=6145062 |s2cid=36606490}}</ref> 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,<ref>FDA. "Subchapter E - Animal Drugs, Feeds, and Related Products; § 582.1666. Propylene glycol." ''Code of Federal Regulations,'' {{USCFR|21|582|1666}}</ref> with an LD₅₀ of 9&nbsp;mL/kg. The LD₅₀ is higher for most laboratory animals (20&nbsp;mL/kg).<ref>{{Cite book |author1=Peterson, Michael |author2=Talcott, Patricia A. |title=Small animal toxicology |year=2006 |publisher=Saunders Elsevier |location=St. Louis |isbn=978-0-7216-0639-2 |page=997}}</ref> 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.<ref>{{cite web |url=http://www.lyondellbasell.com/techlit/techlit/2275.pdf |title= Propylene glycol and cats |archive-url= https://web.archive.org/web/20150227043018/http://www.lyondellbasell.com/techlit/techlit/2275.pdf |access-date=2013-06-21 |archive-date= 2015-02-27 }}</ref> Heinz body formation from MPG has not been observed in dogs, cattle, or humans.

PG has been used in the [[dairy industry]] since the 1950s for cows showing signs of [[ketosis]]. The negative energy balance during the early stages of lactation can cause the animal's body to have lower glucose levels, inducing the liver to make up for this by the conversion of body fat, leading to several health conditions, e.g. [[displaced abomasum]].<ref name=dairy>[https://contraceptivestudies.imedpub.com/using-and-sideeffects-of-propylene-glycol-in-animals.php?aid=22428 Using and Side-effects of Propylene Glycol in Animals], Bulent Elitok, Journal of Reproductive Health and Contraception, April 23, 2018.</ref> PG "reduces the [[propionate]] ratio of [[acetate]] to [[acetaminophen]], while increasing conversion of ruminal PG to propionate, and aid[s] in the closure of energy deficit in cattle."<ref name=dairy />

===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).<ref name=":1">{{Cite journal|last1=Warshaw|first1=Erin M.|last2=Botto|first2=Nina C.|last3=Maibach|first3=Howard I.|last4=Fowler|first4=Joseph F.|last5=Rietschel|first5=Robert L.|last6=Zug|first6=Kathryn A.|last7=Belsito|first7=Donald V.|last8=Taylor|first8=James S.|last9=DeLeo|first9=Vincent A.|date=January 2009|title=Positive patch-test reactions to propylene glycol: a retrospective cross-sectional analysis from the North American Contact Dermatitis Group, 1996 to 2006|journal=Dermatitis: Contact, Atopic, Occupational, Drug|volume=20|issue=1|pages=14–20|issn=2162-5220|pmid=19321115|doi=10.2310/6620.2008.08039|s2cid=959002 |display-authors=3}}</ref><ref>{{Cite journal|last1=Lessmann|first1=Holger|last2=Schnuch|first2=Axel|last3=Geier|first3=Johannes|last4=Uter|first4=Wolfgang|date=November 2005|title=Skin-sensitizing and irritant properties of propylene glycol|journal=Contact Dermatitis|volume=53|issue=5|pages=247–259|doi=10.1111/j.0105-1873.2005.00693.x|issn=0105-1873|pmid=16283903|s2cid=13006333|doi-access=free}}</ref><ref>{{Cite journal|last1=Wetter|first1=David A.|last2=Yiannias|first2=James A.|last3=Prakash|first3=Amy V.|last4=Davis|first4=Mark D. P.|last5=Farmer|first5=Sara A.|last6=el-Azhary|first6=Rokea A.|display-authors=3|date=November 2010|title=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=Journal of the American Academy of Dermatology|volume=63|issue=5|pages=789–798|doi=10.1016/j.jaad.2009.11.033|issn=1097-6787|pmid=20643495}}</ref> 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%).<ref name=":1" /> Investigators believe that the incidence of allergic contact dermatitis to propylene glycol may be greater than 2% in patients with [[Dermatitis|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.<ref name="AMA-DEA1994">{{citation | publisher = American Medical Association, Council on Drugs|year=1994| title = AMA Drug Evaluations Annual 1994|page=1224}}</ref>

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.<ref name=":0">{{Cite journal|last1=Jacob|first1=Sharon E.|last2=Scheman|first2=Andrew|last3=McGowan|first3=Maria A.|date=January–February 2018|title=Propylene Glycol|journal=Dermatitis: Contact, Atopic, Occupational, Drug|volume=29|issue=1|pages=3–5|doi=10.1097/DER.0000000000000315|issn=2162-5220|pmid=29059092|s2cid=24598433}}</ref><ref>{{Cite web|url=https://www.mdedge.com/clinicianreviews/article/176541/contact-dermatitis/allergen-year-may-be-nearer-you-think|title=Allergen of the year may be nearer than you think|website=www.mdedge.com|language=en|access-date=2019-04-08}}</ref> 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.<ref>{{Cite journal|author1=Lalla SC |author2=Nguyen H |author3=Chaudhry H |author4=Killian JM |author5=Drage LA |author6=Davis MDP |author7=Yiannias JA |author8=Hall MR. |display-authors=3 |year= 2018|title=Patch Testing to Propylene Glycol: The Mayo Clinic Experience. |journal=Dermatitis |volume=29 |issue=4 |pages= 200–205|doi=10.1097/DER.0000000000000393 |pmid= 29923851|s2cid= 49311147}}</ref> 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|vitamin B₁₂]]-dependent enzymes, which convert it to [[propionaldehyde]].<ref name=biodeg>{{cite journal |doi=10.1007/s00203-003-0601-0 |title=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 |year=2003 |last1=Leal |first1=Nicole A. |last2=Havemann |first2=Gregory D. |last3=Bobik |first3=Thomas A. |journal=Archives of Microbiology |volume=180 |issue=5 |pages=353–361 |pmid=14504694 |bibcode=2003ArMic.180..353L |s2cid=44010353}}</ref>

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.<ref name="UNEP"/>, UNEP Publications, SIAM 11, U.S.A, January 23–26, 2001, page 21.</ref> 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&nbsp;mg/L in a study with ''[[rainbow trout|Oncorhynchus mykiss]]''. Similarly, the lethal concentration determined in marine fish is a 96-h LC50 of >10,000&nbsp;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 [[Microorganism|microbial populations]] decompose propylene glycol.<ref>{{Cite report |date=April 2012 |title=Environmental Impact and Benefit Assessment for the Final Effluent Limitation Guidelines and Standards for the Airport Deicing Category |url=https://www.epa.gov/eg/airport-deicing-effluent-guidelines-documents |publisher=U.S. Environmental Protection Agency (EPA) |location=Washington, D.C. |id=EPA 821-R-12-003}}</ref>{{rp|2–23}}

==References==

{{Reflist|30em}}

==External links==

{{commons category|Propane-1,2-diol}}

* [https://www.atsdr.cdc.gov/phs/phs.asp?id=1120&tid=240 Agency for Toxic Substances and Disease Registry]

* [http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_006e/0901b8038006e13c.pdf?filepath=propyleneglycol/pdfs/noreg/117-01785.pdf%26fromPage=GetDoc Alton E. Martin - Frank H. Murphy, DOW CHEMICAL COMPANY]

* [https://www.propylene-glycol.com/ Propylene glycol] website

* [http://webbook.nist.gov/cgi/cbook.cgi?ID=C57556 WebBook page for C3H8O2]

* [https://www.atsdr.cdc.gov/csem/csem.html ATSDR - Case Studies in Environmental Medicine: Ethylene Glycol and Propylene Glycol Toxicity] U.S. [[Department of Health and Human Services]] (public domain)

* [http://chemindustry.ru/1,2-Propanediol.php Propylene Glycol - chemical product info: properties, production, applications.]

* [http://chemsub.online.fr/name/propylene_glycol.html ChemSub Online: Propylene glycol]

*[https://vetmeds.org/pet-poison-control-list/propylene-glycol/ Propylene Glycol Toxicity in Pets]

[[Category:Household chemicals]]

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[[Category:Cosmetics chemicals]]

[[Category:Food additives]]

[[Category:Excipients]]

[[Category:Alkanediols]]

[[Category:Commodity chemicals]]

[[Category:Vicinal diols]]

[[Category:E-number additives]]