Propylene Glycol
Source
Propylene Glycol (PG) is used in the synthesis of polyester fibers and resins, as a component of automotive antifreeze and coolants, and as a deicing fluid for air crafts. PG is “generally recognized as safe” by the FDA and is a constituent of many cosmetics, processed foods, and tobacco products, and serves as a diluent for oral, dermal, and i.v. drug preparations [1].
Biotransformation
When PG is ingested through food or accidental sources, ~45% of it is metabolized by ADH into lactaldehyde where the other ~55% is excreted by the kidneys unchanged [1].
Toxicokinetics
Regardless of route of exposure, PG readily enters systemic circulation and distributes based on blood flow. The serum half life of PG is 2-4 hours [1]. The toxic effects are a result of lactic acid build up, which normally is transformed and enters the Krebs cycle to produce glucose, as shown in the diagram above [2]. The rate limiting step in PG metabolism is the conversion of PG into lactaldehyde, preventing the accumulation of lactic acid in the system and allowing more PG to be excreted through the kidneys [1].
Carcinogenicity
A chronic feeding study conducted on rats showed no signs of mutagenicity or carciongenicity. An expert panel assembled by the National Toxicology Program in 2004 concluded that, based on animal studies, there was negligible concern for adverse development and reproductive toxicity from PG in humans [1].
Target organ(s)
No organ system has been identified as a target for PG toxicity because of the low amounts of adverse events, especially as PG has been historically used in medicine [3]. One study conducted in 7 day old mice dosed with 8 hour treatment with saline vs PG results are described below, the dark stain indicates cellular apoptosis [4].
Sections from postnatal day 7 (P7) mouse brain following 8-h treatment with saline or propylene glycol (PG) stained immunohistochemically with antibodies to activated caspase-3 (AC-3). Saline brains (a–d) showed a pattern of sparse AC-3-positive neurons (white arrows) that is typical of physiological cell death, whereas PG triggered widespread neuroapoptosis in many brain regions (e–h). In the caudate/putamen (CPu), cells appeared to be in a later stage of the apoptotic process (staining localized to intact condensed cell bodies, white arrowheads). Top images: original magnification ×10. High-powered photomicrographs: original magnification ×20 [4].
Signs and symptoms of toxicity
Symptoms of metabolic acidosis as a result of lactic acid build up are described below:
Genetic susceptibility or heritable traits
According to the CDC, populations with high susceptibility are [3]:
- the elderly with declining organ function
- people with unusual chemical exposure history
- heavy users of alcohol
- the youngest of the population with immature and developing organs
Historical or unique exposures
As described above, exposure to PG is common and found in many everyday items such as makeup and medications. Workers who are involved in the manufacture or use of solutions containing PG are exposed to higher concentrations than the general population. Including those involved in theatrical performances that use smoke/fog machines, which are created using PG [3].
Treatments
Treatment of PG poisoning is aimed at preventing metabolic acidosis effects by administering sodium bicarbonate to buffer acidic environment. Activated charcoal is not recommended [5].
Biomarkers
PG can be identified in the blood only a short time after a large exposure. Once the PG is metabolized and excreted, there are no other biomarkers that indicate toxic exposure [3].
References for Further Information:
- Bruckner J, Anand S, Warren D. Chapter 24: Toxic Effects of Solvents and Vapors. Casaretts and Doull’s Toxicology: The Basic Science of Poisons, 8e.
- Busti A. Medications Containing Propylene Glycol and Risk of Anion Gap Metabolic Acidosis. Evidence-Based Medicine Consult. Aug 2015. Available from: https://www.ebmconsult.com/articles/medications-containing-propylene-glycol-risk-anion-gap-metabolic-acidosis
- Toxicological Profile for Propylene Glycol. U.S. Department of Health and Human Services. Sep 1997. Available from: https://www.atsdr.cdc.gov/ToxProfiles/tp189.pdf
- Lau K, Swiney B, Reeves N, Noguchi K, Farber N. Propylene glycol produces excessive apoptosis in the developing mouse brain, alone and in combination with phenobarbital. Pediatric Research. 15 Dec 2011;71(54-62).
- Environmental Health and Medicine Education. Ethylene Glycol and Propylene Glycol Toxicity How Should Patients Exposed to Ethylene Glycol Be Treated? Agency for Toxic Subsntaces and Disease Registry. 3 Oct 2007. Available from: https://www.atsdr.cdc.gov/csem/csem.asp?csem=12&po=13