Propylene glycol what is it?
Propylene Glycol, or propane-2, 2-diol, is a synthetic diol alcohol that absorbs water. Its chemical formula is C3H8O2. It has an atomic weight of 76.095 g-mol-1 and a density of 1.036 g/cm3.
Typically propylene glycol is a colorless and clear liquid at atmospheric temperatures. It has a melting point of -74 F and a boiling point of 370.8 F. (1)
In industrial settings, propylene glycol is produced through the hydration of propylene oxide and the addition of sulfuric acid or alkali which produces a solution with 20% propylene glycol and 1.5% propylene glycol.(2)
In the laboratory, S-propanediol glycol is produced through the following reaction:
Propylene glycol is typically used in the production of resins and polyester fibers. It also is used as antifreeze, waterbased acrylic paints, coolants, humectant solvent, pharmaceuticals and food additive. (3)
As a solvent, propylene glycol is used in drugs such as:
Biotransformation studies have been performed to understand why ethylene glycol causes toxic effects.
There are two proposed mechanisms of propylene glycol metabolism:
The first is as follows:
Ethylene glycol is transformed in the liver by alcohol dehydrogenase to glyceraldehyde. Aldehyde dehydrogenase causes glyceraldhyde to become glycolic acid. The glycolic acid then be comes glyoxylic acid. At this stage there are several different byproducts which are produced. With thiamine and magnesium interacts, alpha-hydroxy-beta-ketoadipic acid is produced. With pyridoxine, glycine is produced. Additionally, oxalic acid, formic acid and gamma-hydroxy-alpha-ketoglutaric acid is produced. (4)
This pathway is described below in the following photo:
The second proposed metabolism is as follows:
Propane-2, 2-diol is transformed in the liver by alcohol dehydrogenase to DL-lactaldehyde. DL-lactaldehyde binds to the enzyme alcohol dehydrogenase, which causes methylglyoxal to be formed. Then the methylglyoxal is reduced by glutathione to D-lactate. DL-lactaldehyde can also be transformed by the enzyme alcohol dehydrogenase, into DL-Lactate which is transformed in the liver and used in gluconeogenesis to make glucose. (5)
The pathway is also described by the following photo:
Toxicokinetics of Propylene Glycol:
Propylene Glycol typically is inhaled, ingested or absorbed through the skin.
Propylene Glycol is actually considered very safe and there have been no human deaths from exposure. Propylene glycol is actually cleared by the body within 48 hours of exposure.
Since propylene glycol is not considered hazardous its toxicokinetics is has not been thoroughly investigated.
That being said, when ingested it is absorbed quickly through the gastrointestinal tract. It reaches Tmax within an hour of ingestion. With constant small dosing through food or other sources it can build up to toxic levels in the blood.
If propylene glycol is on skin, say when giving dermal therapeutics, it can be seen in the blood and in the urine at low levels. In one burn victim study, as long as blood concentrations were below 1.3 mg/mL the patients survived. In general, propylene glycol is not readily absorbed through the skin unless it also is mixed with another acid.
Mechanism of Action of Propylene Glycol- toxicity:
The mechanism of action of propylene glycol is due to the effects of glycolic acid and oxalic acid.
Glycolic acid will build up as propylene glycol is broken down and will cause a metabolic acidosis in the patient.
For an explanation of metabolic acidosis check out this youtube video:
Normally, oxalic acid cause the binding of calcium throughout the body, which can cause crystal formation in the body. Normally this can cause kidney issues. Fortunately, propylene glycol does not cause crystal formation but rather just a hypocalcaemia in the patient.(5)
More information about oxalic acid poisoning can be read in this really interesting article!
Dassanayake, Uditha, and Christeine Ariaranee Gnanathasan. “Acute Renal Failure Following Oxalic Acid Poisoning: a Case Report.” Journal of Occupational Medicine and Toxicology (London, England), BioMed Central, 14 Sept. 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC3527234/.
Carcinogenicity and Teratogenicity of Propylene Glycol:
Propylene Glycol is actually one of the safer solvents which we have studied in regards to carcinogenicity and teratogenicity. There is no evidence that propylene glycol is a teratogen, genotoxic or carcinogenic. This has been shown in rays, cell lines and mice. (5)
Target Organs of Propylene Plycol:
Propylene glycol is considered safe so it actually doesn’t cause many issues but if a person is immunocompromised, typically the renal and hepatic system is damaged.
If inhaled an acute respiratory acidosis can occur.
If inhalation is severe enough, cardiac and pulmonary failure could occur. This has not been documented.
Skin irritation can also occur.(5)
Signs and Symptoms of Propylene Glycol:
Signs of propylene glycol tend to be nonspecific but can present as follows.
Initial inebriation leads to the neurologic effects of: stupor, convolusions, and neurotoxicity. (8)
Treatment for Propylene Glycol?
*****Below is adapted from my last Benzimidazole post:(9)****
As with any toxicity case which presents 6 steps are traditionally taken for management:(8)
- Stabilizing the patient to ensure open airways, breathing and proficient circulation.
- Evaluating how stabile the patient is through complete blood counts, blood gas and other assays.
- Prevention of further contamination through removing clothing which has been exposed.
- Enhancement of elimination through the use of activated charchoal. This has been found to be especially useful with selenium toxicity.
- There is no antidote to selenium poisioning.
- Supportive care to the patient through bronchodilators or mechanical ventilation.
Management is typically supportive but if severe, hemodialysis can be performed.
Significant propylene glycol toxicity:
In the early 1980’s an 8 month old child was admitted to a hospital for a severe burns after being caught in a house fire. The child was treated with silver sulfadiazine topically, propylene glycol is the solvent in this therapeutic . The child went into cardiorespiratory arrest after administration but it was not determined whether this was due to the fire, smoke or the drug itself. This is incredibly sad story was the only death which could even remotely be linked to propylene glycol. (10)
(1) The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. Merck & Co. 1989. ISBN 978-0911910285.
(2) “1,2-propanediol: chemical product info at CHEMINDUSTRY.RU”. Retrieved 3 October2018.
(3): Bradley, Jean-Claude; Abraham, Michael H; Acree, William E; Lang, Andrew (2015). “Predicting Abraham model solvent coefficients”. Chemistry Central Journal. 9 (1): 12. doi:10.1186/s13065-015-0085-4. ISSN 1752-153X. PMC 4369285. PMID 25798192.
(4) “Environmental Health and Medicine Education.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.atsdr.cdc.gov/csem/csem.asp?csem=12&po=8.
(5) “Use of Race and Ethnicity in Public Health Surveillance: Summary of the CDC/ATSDR Workshop.” PsycEXTRA Dataset, 1993, doi:10.1037/e546762006-001.
(6) “Renal Function Markers – Kidney Disease.” ARUPConsult, arupconsult.com/content/renal-function-markers.
(7) “Elevated Liver Enzymes.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 11 Jan. 2018, www.mayoclinic.org/symptoms/elevated-liver-enzymes/basics/definition/sym-20050830.
(8) Plahovinsak, J. “PHRM7588: Toxic Substances.” Carmen.com, 2019.
(9) Palillo, M. 2019. Benzimidazoles- Fungi and Helminths Beware! https://u.osu.edu/palillo.1/