Propylene Glycol

Propylene glycol is a commonly used ingredient that conditions and moisturizes the skin. It is also added to cosmetic formulations as a stabilizer, fragrance ingredient, solvent and viscosity-decreasing agent.

Effects


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments

C

Dermatitis treatment

Strong

Seems to improves seborrheic dermatitis of the scalp by clearing M. furfur. Also effective in relieving the symptoms of atopic dermatitis.

D

Increased skin hydration

Moderate

Functions as both a humectant and occlusive, drawing water to the stratum corneum and preventing it from being lost through evaporation.

D

Photoprotection

Mild

Increased the protective efficacy of a mixture of chemical sunscreens against UVB radiation in one study.

Looking to buy skin care products containing Propylene Glycol?

Buy from Amazon.com.

Scientific Research


Caution: Please read wisderm.com's medical disclaimer.

Table of contents:

1. Sources

1.1 In cosmetics

Propylene glycol or 1,2-propane diol is an alcohol that functions as a skin conditioner, viscosity-decreasing agent, solvent and fragrance ingredient in cosmetics. Its frequency and concentration of use has increased over the years. According to information submitted to the FDA, in 1994 propylene glycol was used in 5,676 products at concentrations up to 50%, but this had risen to 9,747 products at concentrations of up to 73% by 2009. In bath oils, tablets or salts it is used in even higher concentrations of up to 99%.[1]

Overall, propylene glycol was reported to be used in 26% of all cosmetic formulations and 54% of all deodorants.[1] It is also quite frequently used in moisturizers, as discovered by an analysis of 276 moisturizers that detected it in 20% of the products.[2]

1.2 In food

Propylene glycol is generally recognized as safe (GRAS) by the US FDA as a direct food additive. It is permitted at maximum levels of 5% for alcoholic beverages, 24% for confections and frostings, 2.5% for frozen dairy products, 97% for seasonings and flavourings, 5% for nuts and nut products, and 2% for all other food categories.[3] According to the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the acceptable daily intake (ADI) of propylene glycol is 25 mg/kg/bw/day.[4]

1.3 In pharmaceuticals

Propylene glycol is used as an active ingredient in a number of FDA-approved drug products. It has been approved at concentrations up to 98.09% for topical drugs, 94.925% in auricular solutions and 92% in oral solutions.[5]

2. Bioavailability

The cumulative penetration of propylene glycol into excised hairless mouse skin from a ternary cosolvent containing 84% propylene glycol, 10% oleic acid and 6% dimethyl isosorbide was 57% of the applied dose, over a 24-hour period. The propylene glycol did not seem to reach the dermis.[6]

A smaller percentage (23% of the applied dose) has been estimated for human skin, based on the measured absorption of propylene glycol across excised human abdominal skin.[7] Another experiment observed that propylene glycol failed to cross the stratum corneum even after 2 hours, supporting the notion that propylene glycol is poorly absorbed by the skin.[8]

In an in vivo study, propylene glycol applied to the fingertip of a human subject reached a depth of 6 µm after 32 minutes. The highest concentration at this depth was only 0.2%. After more than 2.5 hours, the maximum concentration of propylene glycol was found at a depth of 3-4 µm Hence, it was suggested that propylene glycol diffuses only to a depth of 6-7 µm in human skin. Because the thickness of the stratum corneum of the human fingertip is >10 µm, propylene glycol therefore does not reach the dermis.[9]

Oleic acid enhances the penetration of propylene glycol.[10][11]

3. Effects on the skin

3.1 Moisturizing effect

Propylene glycol is a humectant.[8] It dries on the skin to a hygroscopic film that retains moisture by forming a barrier against the evaporation of water, and is also thought to function by an osmotic mechanism that attracts water to the stratum corneum,[12][13] which accounts for the observation that it leads to a transient swelling of the stratum corneum.[14] It also helped enhance the occlusive properties of nanostructured lipid carrier (NLC) formulations by reducing transepidermal water loss (TEWL) from the skin.[15]

Propylene glycol does not hydrate the skin as well as glycerin, probably because glycerin's superior hygroscopic character enables it to better modulate water fluxes in the stratum corneum and preserve the skin barrier more effectively.[16][17]

However, one study found that propylene glycol had no significant hydrating effect, at least when applied as an oil-in-water emulsion.[17] Another noted that propylene glycol dehydrates rather than hydrates the skin, as shown by a decrease in bound water content, due to alterations in the protein domains of the stratum corneum.[18]

3.2 Antimicrobial effect

Propylene glycol is both an antibacterial and antifungal agent. At high concentrations, it is effective against the bacteria S. aureus, S. epidermidis, S. pyogenes, S. mitis and E. coli, as well as the yeasts C. albicans and M. furfur.[19][20] As a result, it is effective at treating skin conditions caused by these pathogens, including Tinea versicolor, Malassezia folliculitis and seborrheic dermatitis.[21][22][23][24][25]

3.3 Treatment of dermatitis

Propylene glycol has proven to be an effective treatment for seborrheic dermatitis of the scalp,[23][25] which often presents as dandruff in adolescents and adults.[26]

In a double-blind, controlled study of 39 patients, 16 out of 18 (89%) patients treated with a solution containing 15% propylene glycol, 50% ethanol and 35% water showed healing, compared to 6 out of 19 (32%) patients treated with 50% ethanol and 50% water. The number of M. furfur organisms was reduced significantly after treatment with the solution containing propylene glycol, but not with the other solution, indicating that propylene glycol's antifungal effect was responsible for the healing.[27] 2 other double-blind and placebo-controlled studies likewise found that topical solutions of urea, lactic acid and propylene glycol led to clinically meaningful improvements in seborrheic dermatitis endpoints.[28]

Propylene glycol's moisturizing properties also make it useful in improving atopic dermatitis, which is characterized by dry skin. Propyless, a commercially available lotion based on propylene glycol, was at least as effective as Fenuril, a commercial cream based on urea and sodium chloride, in alleviating the cutaneous symptoms of atopic dermatitis in 55 patients enrolled in a randomized, single-blind comparative study.[12]

3.4 Treatment of ichthyosis

Mixtures of propylene glycol and water are very effective in treating ichthyosis when applied under occlusive dressings,[29][30] and is even more effective at removing its keratolytic scales with the addition of salicylic acid to the formulation.[31] The commercial cream Locobase Repair, which contains 20% propylene glycol + 5% lactic acid, was superior to 3 other cream formulations in improving lamellar ichthyosis in 20 patients. It reduced xerosis, scaling and skin roughness, and improved skin hydration. It also produced the most rapid effect, with a response rate of 63% after 4 weeks.[32]

3.5 Other effects and uses

One study has suggested that the addition of propylene glycol can increase the capacity of chemical sunscreening agents to protect against UVB irradiation in both non-photosensitive subjects and patients suffering from a variety of photodermatoses.[33]

Another study revealed that propylene glycol inhibited the activity of stratum corneum aspartic proteinases, which may serve as a marker for skin aging or for certain skin disorders.[34]

Propylene glycol is also used to stabilize formulations. It helps prevent the aggregation of titanium dioxide nanoparticles, maintaining them in a monodispersed state,[35] enhances the physical stability of nanostructured lipid carriers (NLC) formulations,[15][36] and inhibited the decomposition of deoxyarbutin when used together with glycerin as the inner hydrophilic phase of anhydrous emulsions.[37]

4. Safety

Propylene glycol and polypropylene glycols, the polymers of propylene glycol were originally reviewed by the Cosmetic Ingredient Review Expert Panel in 1994 and found to be safe for use in cosmetic products at concentrations up to 50%.[38] In 2012, a re-review determined that concentrations up to 73% are safe and do not present a sensitization risk.[1]

4.1 Cytotoxicity

Propylene glycol is moderately cytotoxic to human fibroblasts and keratinocytes. Its IC₅₀ value for proliferation inhibition was 280 mM for fibroblasts and 85 mM for keratinocytes. It also inhibited collagen contraction by fibroblasts with an IC₅₀ of 180 mM, caused keratinocytes and fibroblasts to undergo changes in cell shape, and induced irreversible cell damage in both cultures at a concentration of 660 mM.[39]

4.2 Adverse skin reactions

Propylene glycol is capable of producing both primary irritant skin reactions and allergic sensitization when applied topically,[40][41][42][43] though it appears to be only slightly irritating and the risk of sensitization is very low for uncompromised skin.[44] Some researchers have proposed classifying skin reactions to propylene glycol into 4 groups: irritant contact dermatitis, allergic contact dermatitis, non-immunologic contact urticaria, and subjective or sensory irritation.[45] Propylene glycol does not seem to be a photoallergen however, as it did not produce any photoallergic responses in a provocative photopatch test on 82 subjects with photoallergic contact dermatitis.[46]

Prospective studies and retrospective analyses of patch test data have found widely varying positive reaction rates, ranging from 0% to as high as 12.5%.[47][48] In North America, the positive reaction rate seems to have hovered around 3.5%,[49][50][51][52][53] though patch testing results from Mount Sinai Medical Center identified propylene glycol as an allergen in 7.8% of cases, making it one of the most frequent contact allergens.[54] In Europe, positive reactions rates to propylene glycol was 1% in Austria,[55] 0.4% in the Czech Republic,[56] 0.8% in Denmark[57] and 0% in Turkey.[47] Propylene glycol was also one of the top allergens in German children and adolescents.[58] At least part of the observed variance is probably due to differences in test protocols and concentrations.

There are numerous case reports of adverse skin reactions to propylene glycol.[59][60][61][62][63][64][65] Personal care products are known to be a common source of propylene glycol exposure leading to allergic or irritant contact dermatitis,[50] but contact allergy and contact dermatitis to propylene glycol can also arise due to its inclusion in topical medicines[66][67][68][69][70][71][72][73][74][75] ultrasonic gels[76][77] and ECG electrode gels.[78][79] There have also been isolated reports of contact sensitivity to propylene glycol in a lubricant jelly[80] and in an antiperspirant.[81] Avoidance of propylgene glycol-containing products can lead to improvement of contact dermatitis.[82][83]

Further, the addition of propylene glycol to an isopropanol vehicle enhanced the irritant reaction of benzoic acid in a non-occlusive test of 15 human subjects.[84] In rare cases, overdoses on propylene glycol can cause intoxication in young children, leading to central nervous system depression and metabolic acidosis.[85][86]

4.3 Enhanced penetration

Propylene glycol acts as a permeation enhancer, possibly by altering the barrier function of the skin or by increasing the solution capacity within the stratum corneum.[6][87][88] It has been demonstrated to increase the skin penetration of the model substance pyrene butyric acid,[10] the flavonoid hesperetin,[89] the sunscreen oxybenzone[90][91] as well as many drugs[92][93][94][95][96] including topical glucocorticoids such as hydrocortisone.[97][98][99]

4.4 Little evidence of genotoxicity

Propylene glycol was not mutagenic in Ames tests with or without metabolic activation, up to a concentration of 10,000 µg/plate. It was also not mutagenic not in mitotic recombination or base pair substitution assays, in a micronucleus test or in a hamster embryo cell transformation assay. Sister chromatid exchange assays using Chinese hamster cell lines showed inconsistent results, but propylene glycol did not induce chromosomal aberrations in separate studies on human cultured fibroblasts and human embryonic cells.[38]

4.5 No evidence of carcinogenicity

Propylene glycol has not been found to be carcinogenic whether the method of administration is oral, dermal, or via subcutaneous injection. For instance, dermal application of undiluted propylene glycol to Swiss mice in a lifetime study produced no significant carcinogenic effects.[38]

4.6 Reproductive and developmental effects

The National Toxicology Program has evaluated the potential human reproductive and developmental effects of propylene glycol and concluded that there is no cause for concern. High oral doses of propylene glycol did not affect fertility in mice or produce developmental toxicity in their offspring, and the pharmacokinetics of propylene glycol indicates that the lack of adverse effects observed in these laboratory animals is relevant to humans.[100][101]

Scientific References


  1. Fiume MM, et. al. Safety assessment of propylene glycol, tripropylene glycol, and PPGs as used in cosmetics. Int J Toxicol. (2012)
  2. Zirwas MJ, Stechschulte SA. Moisturizer allergy: diagnosis and management. J Clin Aesthet Dermatol. (2008)
  3. US Food and Drug Administration. CFR - Code of Federal Regulations Title 21, Part 184, Subpart B, Section 184.1666. Code of Federal Regulations. (2013)
  4. Joint FAO/WHO Expert Committee on Food Additives. Toxicological evaluation of certain food additives with a review of general principles and of specifications. World Health Organization Technical Report Series. (1973)
  5. US Food and Drug Administration. Inactive Ingredient Search for Approved Drug Products. US FDA. (2014)
  6. Squillante E, et. al. Codiffusion of propylene glycol and dimethyl isosorbide in hairless mouse skin. Eur J Pharm Biopharm. (1998)
  7. Fasano WJ, et. al. Dermal penetration of propylene glycols: measured absorption across human abdominal skin in vitro and comparison with a QSAR model. Toxicol In Vitro. (2011)
  8. Vyumvuhore R, et. al. Vibrational spectroscopy coupled to classical least square analysis, a new approach for determination of skin moisturizing agents' mechanisms. Skin Res Technol. (2014)
  9. Notingher I, Imhof RE. Mid-infrared in vivo depth-profiling of topical chemicals on skin. Skin Res Technol. (2004)
  10. Schneider I-M, et. al. Evaluation of drug penetration into human skin ex vivo using branched fatty acids and propylene glycol. Int J Pharm. (1996)
  11. Tanojo H, Junginger HE, Boddé HE. In vivo human skin permeability enhancement by oleic acid: transepidermal water loss and fourier-transform infrared spectroscopy studies. J Control Release. (1997)
  12. Faergemann J, Olsson P, Svensson A. A randomized, single-blind comparison of the efficacy, tolerability and cosmetic acceptance of Propyless or Fenuril treatment of patients with dry skin. Acta Derm Venereol. (2009)
  13. Gloor M. How do dermatological vehicles influence the horny layer? Skin Pharmacol Physiol. (2004)
  14. Corcuff P, et. al. In vivo confocal microscopy of human skin: a new design for cosmetology and dermatology. Scanning. (1996)
  15. Loo Ch, et. al. Effect of compositions in nanostructured lipid carriers (NLC) on skin hydration and occlusion. Int J Nanomedicine. (2013)
  16. Ghosh S, et. al. Ranking of aqueous surfactant-humectant systems based on an analysis of in vitro and in vivo skin barrier perturbation measurements. J Cosmet Sci. (2007)
  17. Bettinger J, et. al. Comparison of different non-invasive test methods with respect to the effect of different moisturizers on skin. Skin Res Technol. (2007)
  18. Shah DK, Khandavilli S, Panchagnula R. Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers. Methods Find Exp Clin Pharmacol. (2008)
  19. Kinnunen T, Koskela M. Antibacterial and antifungal properties of propylene glycol, hexylene glycol, and 1,3-butylene glycol in vitro. Acta Derm Venereol. (1991)
  20. Bäurle G, et. al. The suitability of propylene glycol (1,2-propanediol) as an active antimicrobial adjuvant in ointments. Z Hautkr. (1985)
  21. Faergemann J, Fredriksson T. Propylene glycol in the treatment of tinea versicolor. Acta Derm Venereol. (1980)
  22. Faergemann J. Current treatment of cutaneous Pityrosporum and Candida-infections. Acta Derm Venereol Suppl (Stockh). (1986)
  23. Faergemann J. Short-term treatment of dandruff with a combination of propylene glycol solution and shampoo. Cutis. (1988)
  24. Faergemann J. Pityriasis versicolor. Semin Dermatol. (1993)
  25. Faergemann J. Management of seborrheic dermatitis and pityriasis versicolor. Am J Clin Dermatol. (2000)
  26. Schwartz RA, Janusz CA, Janniger CK. Seborrheic dermatitis: an overview. Am Fam Physician. (2006)
  27. Faergemann J. Propylene glycol in the treatment of seborrheic dermatitis of the scalp: a double-blind study. Cutis. (1988)
  28. Emtestam L, Svensson Å, Rensfeldt K. Treatment of seborrhoeic dermatitis of the scalp with a topical solution of urea, lactic acid, and propylene glycol (K301): results of two double-blind, randomised, placebo-controlled studies. Mycoses. (2012)
  29. Goldsmith LA, Baden HP. Propylene glycol with occlusion for treatment of ichthyosis. JAMA. (1972)
  30. Audebert C. A simple treatment for ichthyosis: occlusive propylen glycol dressings. Ann Dermatol Venereol. (1977)
  31. Baden HP, Alper JC. A keratolytic gel containing salicylic acid in propylene glycol. J Invest Dermatol. (1973)
  32. Gånemo A, Virtanen M, Vahlquist A. Improved topical treatment of lamellar ichthyosis: a double-blind study of four different cream formulations. Br J Dermatol. (1999)
  33. Macleod TM, Frain-Bell W. A study of chemical light screening agents. Br J Dermatol. (1975)
  34. Wormser U, et. al. Noninvasive procedure for in situ determination of skin surface aspartic proteinase activity in animals; implications for human skin. Arch Dermatol Res. (1997)
  35. Gurbani D, et. al. Stable metal oxide nanoparticle formulation for toxicity studies. J Biomed Nanotechnol. (2011)
  36. Hommoss A. Preservative system development for argan oil-loaded nanostructured lipid carriers. Pharmazie. (2011)
  37. Lin CC, et. al. Study on the stability of deoxyArbutin in an anhydrous emulsion system. Int J Mol Sci. (2011)
  38. Cosmetic Ingredient Review Expert Panel. Final Report on the Safety Assessment of Propylene Glycol and Polypropylene Glycols. Int J Toxicol. (1994)
  39. Ponec M, et. al. Use of human keratinocyte and fibroblast cultures for toxicity studies of topically applied compounds. J Pharm Sci. (1990)
  40. Catanzaro JM, Smith JG Jr. Propylene glycol dermatitis. J Am Acad Dermatol. (1991)
  41. Trancik RJ, Maibach HI. Propylene glycol: irritation or sensitization? Contact Dermatitis. (1982)
  42. Primavera G, Berardesca E. Sensitive skin: mechanisms and diagnosis. Int J Cosmet Sci. (2005)
  43. Nater JP, Baar AJ, Hoedemaeker PJ. Histological aspects of skin reactions to propylene glycol. Contact Dermatitis. (1977)
  44. Lessmann H, et. al. Skin-sensitizing and irritant properties of propylene glycol. Contact Dermatitis. (2005)
  45. Funk JO, Maibach HI. Propylene glycol dermatitis: re-evaluation of an old problem. Contact Dermatitis. (1994)
  46. Rodríguez E, et. al. Causal agents of photoallergic contact dermatitis diagnosed in the national institute of dermatology of Colombia. Photodermatol Photoimmunol Photomed. (2006)
  47. Boyvat A, Akyol A, Gürgey E. Contact sensitivity to preservatives in Turkey. Contact Dermatitis. (2005)
  48. Hannuksela M, Pirilä V, Salo OP. Skin reactions to propylene glycol. Contact Dermatitis. (1975)
  49. Eiermann HJ, et. al. Prospective study of cosmetic reactions: 1977-1980. North American Contact Dermatitis Group. J Am Acad Dermatol. (1982)
  50. Warshaw EM, et. al. Positive patch-test reactions to propylene glycol: a retrospective cross-sectional analysis from the North American Contact Dermatitis Group, 1996 to 2006. Dermatitis. (2009)
  51. Zug KA, et. al. The value of patch testing patients with a scattered generalized distribution of dermatitis: retrospective cross-sectional analyses of North American Contact Dermatitis Group data, 2001 to 2004. J Am Acad Dermatol. (2008)
  52. Fransway AF, et. al. North American Contact Dermatitis Group patch test results for 2007-2008. Dermatitis. (2013)
  53. Warshaw EM, et. al. North American Contact Dermatitis Group patch test results: 2009 to 2010. Dermatitis. (2013)
  54. Yoo JY, et. al. Allergic contact dermatitis: patch testing results at Mount Sinai Medical Center. Skinmed. (2010)
  55. Wöhrl S, et. al. Patch testing in children, adults, and the elderly: influence of age and sex on sensitization patterns. Pediatr Dermatol. (2003)
  56. Dastychová E, et. al. Contact sensitization to pharmaceutic aids in dermatologic cosmetic and external use preparations. Ceska Slov Farm. (2004)
  57. Andersen KE, Storrs FJ. Skin irritation caused by propylene glycols. Hautarzt. (1982)
  58. Heine G, et. al. Frequency of contact allergy in German children and adolescents patch tested between 1995 and 2002: results from the Information Network of Departments of Dermatology and the German Contact Dermatitis Research Group. Contact Dermatitis. (2004)
  59. Gonzalo MA, et. al. Allergic contact dermatitis to propylene glycol. Allergy. (1999)
  60. Kuznetsov AV, Erlenkeuser-Uebelhoer I, Thomas P. Contact allergy to propylene glycol and dodecyl gallate mimicking seborrheic dermatitis. Contact Dermatitis. (2006)
  61. Fisher AA. Reactions to popular cosmetic humectants. Part III. Glycerin, propylene glycol, and butylene glycol. Cutis. (1980)
  62. Pevny I, Uhlich M. Allergy against components of medical and cosmetic external preparations. Polyethylene glycol, propylene glycol, hexantriole Hautarzt. (1975)
  63. Andersen KE. Skin reactions caused by propylene glycol. Ugeskr Laeger. (1980)
  64. Morán M, Martin-Pascual A, Armijo Moreno M. Contact eczema caused by propylene glycol. Actas Dermosifiliogr. (1979)
  65. Fisher AA. Letter: Contact dermatitis from stearyl alcohol and propylene glycol. Arch Dermatol. (1974)
  66. el Sayed F, et. al. Contact dermatitis from propylene glycol in Rifocine. Contact Dermatitis. (1995)
  67. Shore RN, Shelley WB. Contact dermatitis from stearyl alcohol and propylene glycol in fluocinonide cream. Arch Dermatol. (1974)
  68. Oleffe JA, Blondeel A, de Coninck A. Allergy to chlorocresol and propylene glycol in a steroid cream. Contact Dermatitis. (1979)
  69. Eun HC, Kim YC. Propylene glycol allergy from ketoconazole cream. Contact Dermatitis. (1989)
  70. Coloe J, Zirwas MJ. Allergens in corticosteroid vehicles. Dermatitis. (2008)
  71. Kim YJ, Kim JH. Allergic contact dermatitis from propylene glycol in Zovirax cream. Contact Dermatitis. (1994)
  72. Aljasser MI, Al-Omair IA. Propylene glycol allergic contact dermatitis. A quick reference guide for propylene glycol-free topical corticosteroids in Saudi Arabia. Saudi Med J. (2013)
  73. Al Jasser M, Mebuke N, de Gannes GC. Propylene glycol: an often unrecognized cause of allergic contact dermatitis in patients using topical corticosteroids. Skin Therapy Lett. (2011)
  74. Farrar CW, Bell HK, King CM. Allergic contact dermatitis from propylene glycol in Efudix cream. Contact Dermatitis. (2003)
  75. Fisher DA. Allergic contact dermatitis to propylene glycol in calcipotriene ointment. Cutis. (1997)
  76. Horiguchi Y, et. al. A case of allergic contact dermatitis from propylene glycol in an ultrasonic gel, sensitized at a leakage skin injury due to transcatheter arterial chemoembolization for hepatocellular carcinoma. Int J Dermatol. (2005)
  77. Eguino P, et. al. Allergic contact dermatitis due to propylene glycol and parabens in an ultrasonic gel. Contact Dermatitis. (2003)
  78. Uter W, Schwanitz HJ. Contact dermatitis from propylene glycol in ECG electrode gel. Contact Dermatitis. (1996)
  79. Connolly M, Buckley DA. Contact dermatitis from propylene glycol in ECG electrodes, complicated by medicament allergy. Contact Dermatitis. (2004)
  80. Fisher AA, Brancaccio RR. Allergic contact sensitivity to propylene glycol in a lubricant jelly. Arch Dermatol. (1979)
  81. Agren-Jonsson S, Magnusson B. Sensitization to propantheline bromide, trichlorocarbanilide and propylene glycol in an antiperspirant. Contact Dermatitis. (1976)
  82. Lu R, Katta R. Iatrogenic contact dermatitis due to propylene glycol. J Drugs Dermatol. (2005)
  83. Lowther A, McCormick T, Nedorost S. Systemic contact dermatitis from propylene glycol. Dermatitis. (2008)
  84. Lahti A, Noponen SL. Propylene glycol in an isopropanol vehicle enhances immediate irritant reactions to benzoic acid. Contact Dermatitis. (1998)
  85. Glover ML, Reed MD. Propylene glycol: the safe diluent that continues to cause harm. Pharmacotherapy. (1996)
  86. Guillot M, et. al. Home environment and acute propylene glycol intoxication in a two-year old. An unusual case report. Arch Pediatr. (2002)
  87. Mohammed D, et. al. Influence of skin penetration enhancers on skin barrier function and skin protease activity. Eur J Pharm Sci. (2014)
  88. Savic S, et. al. Topical vehicles based on natural surfactant/fatty alcohols mixed emulsifier: The influence of two polyols on the colloidal structure and in vitro/in vivo skin performance. J Pharm Sci. (2009)
  89. Tsai YH, et. al. In vitro permeation and in vivo whitening effect of topical hesperetin microemulsion delivery system. Int J Pharm. (2010)
  90. Mbah CJ. The effect of glycerol, propylene glycol and polyethylene glycol 400 on the partition coefficient of benzophenone-3 (oxybenzone). Pharmazie. (2007)
  91. Fernandez C, et. al. LC analysis of benzophenone-3: II application to determination of 'in vitro' and 'in vivo' skin penetration from solvents, coarse and submicron emulsions. J Pharm Biomed Anal. (2000)
  92. Arellano A, et. al. Influence of propylene glycol and isopropyl myristate on the in vitro percutaneous penetration of diclofenac sodium from carbopol gels. Eur J Pharm Sci. (1999)
  93. Levang AK, Zhao K, Singh J. Effect of ethanol/propylene glycol on the in vitro percutaneous absorption of aspirin, biophysical changes and macroscopic barrier properties of the skin. Int J Pharm. (1999)
  94. Niazy EM, Molokhia AM, El-Gorashi AS. Effect of vehicle and drug concentration on transdermal delivery of dihydroergotamine using excised animal skin. Drug Dev Ind Pharm. (1990)
  95. Shahzad Y, et. al. Applying response surface methodology to optimize nimesulide permeation from topical formulation. Pharm Dev Technol. (2013)
  96. Watkinson RM, et. al. Optimisation of cosolvent concentration for topical drug delivery - II: influence of propylene glycol on ibuprofen permeation. Skin Pharmacol Physiol. (2009)
  97. Basse LH, Groen D, Bouwstra JA. Permeability and lipid organization of a novel psoriasis stratum corneum substitute. Int J Pharm. (2013)
  98. Bendas B, Schmalfuβ U, Neubert R. Influence of propylene glycol as cosolvent on mechanisms of drug transport from hydrogels. Int J Pharm. (1995)
  99. Faergemann J, et. al. Pentane-1,5-diol as a percutaneous absorption enhancer. Arch Dermatol Res. (2005)
  100. National Toxicology Program. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Propylene Glycol (PG). NTP CERHR MON. (2004)
  101. Fowles JR, Banton MI, Pottenger LH. A toxicological review of the propylene glycols. Crit Rev Toxicol. (2013)