Agency for Toxic Substances and Disease Registry
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Learning Objectives |
Upon completion of this section, you should be able to
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Introduction |
In contrast to ethylene glycol, a potent cause of acute toxicity in humans, propylene glycol is a “generally recognized as safe” (GRAS) additive for foods and medications. Propylene glycol rarely causes toxic effects, and then only under very unusual circumstances. |
Uses |
Propylene glycol is a Generally Recognized as Safe (GRAS) food additive that is widely used in
In certain medicines, cosmetics, and food products, propylene glycol acts as
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Concentrations in Food |
Concentrations in foods range from <0.001% in eggs and soups to about 15% in some seasonings and flavorings. Propylene glycol is an FDA-approved additive for military dietary rations (Agency for Toxic Substances and Disease Registry 1997). |
Use in Textiles |
The largest amounts of propylene glycol are used in the textile industry, where it is an intermediate in polyester fiber production. |
Synonyms |
Synonyms for propylene glycol include
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Special Uses |
Aerosolized propylene glycol can provide dense “smoke” without flames. It is used
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De-Icing |
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Sources of Exposure |
In the general population, propylene glycol exposure occurs primarily through ingestion of food and medications and through dermal contact with cosmetics or topical medications. Propylene glycol is used as a solvent in cosmetics and pharmaceuticals, in various formats
For example, it makes up 40% of intravenous phenytoin (Dilantin) and other injectable medications (Meditext 2004). No adverse health effects are likely to occur from normal use of these products. However, heavy use of injectable medications with propylene glycol (Louis, Kutt et al. 1967; Seay, Graves et al. 1997; Yorgin, Theodorou et al. 1997; Wilson, Reardon et al. 2000), or prolonged and extensive topical application on compromised skin, such as burns (Peleg, Bar-Oz et al. 1998), has caused excess levels of propylene glycol in the body. |
Who is at Risk? |
Propylene glycol toxicity has been reported only rarely and in unusual circumstances. For example, toxicity may result from
Those at special risk include
Increased sensitivity (Reprotext 2004) may be seen in people with pre-existing
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Biological Fate |
Absorption of propylene glycol from the gastrointestinal tract is rapid: maximal plasma concentrations in humans occur within 1 hour after ingestion. MetabolitesPropylene glycol is metabolized in the liver by alcohol dehydrogenase to
Both of these metabolites are normal constituents of the citric acid cycle and are further metabolized to
About 45% of an absorbed propylene glycol dose is excreted by the kidneys unchanged or as the glucuronide conjugate. Half-LifeThe elimination half-life of propylene glycol is about 4 hours. |
Physiological Effects |
Topical application to injured skin (as a component of burn creams) or intravenous administration (as an excipient in certain anticonvulsant, antianginal, antibiotic, or other medications) has sometimes been associated with
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Central Nervous System Effects |
CNS depression is the primary manifestation of acute propylene glycol poisoning. |
Metabolic Effects |
Metabolic acidosisMetabolic conversion of propylene glycol to lactic and pyruvic acids can contribute to metabolic acidosis and an abnormal anion gap. HyperosmolalityUnchanged propylene glycol circulating in the body causes hyperosmolality. |
Examples of Propylene Glycol Poisoning |
Although propylene glycol is nontoxic under normal conditions, it can cause poisoning in rare and unusual circumstances. In one case, an 8-month-old infant with large surface area second-degree and third-degree burns was treated for many days with topical silver sulfadiazine containing a large amount of propylene glycol. The infant developed acute metabolic acidosis and cardiorespiratory arrest. The daily dose of propylene glycol was 9,000 mg/kg. Serum propylene glycol levels were highest on day 14 (1,059 mg/dL) when the osmolal gap was 75 mOsm/L (normal: <10 mOsm/L) (Fligner, Jack et al. 1985). |
Phenytoin and Propylene Glycol |
Propylene glycol is a common diluent for injectable medications. It constitutes 40% of the intravenous form of phenytoin. This high concentration is necessary to
In some patients given intravenous phenytoin, propylene glycol was reported to cause
Fatal cardiac and respiratory arrests have also been reported, but these effects may have been due to the cardioactive phenytoin. (Donovan and Cline 1991). |
Lack of Renal Effects |
Propylene glycol has not been associated with nephrotoxicity caused by calcium oxalate in humans. Unlike ethylene glycol, propylene glycol is not metabolized to oxalic acid, so calcium oxalate is not deposited in the kidneys (Agency for Toxic Substances and Disease Registry 1997). |
Contact Dermatitis |
Propylene glycol can be a skin sensitizer, resulting in allergic contact dermatitis in some individuals (Reprotext 2004). |
Comparison with Ethylene Glycol |
In comparing the toxicity of ethylene glycol with that of propylene glycol, LaKind et al. (1999) stated that “From the standpoint of lethality, acute effects, and reproductive, developmental, and kidney toxicity, the toxicity of ethylene glycol exceeds that of propylene glycol (LaKind, McKenna et al. 1999). Further, localized dermal effects from ethylene glycol and propylene glycol are both mild, with data suggesting that propylene glycol may have a skin contact sensitization potential. Finally, propylene glycol exposure in laboratory animals has been associated with reversible hematological changes; no data were located for ethylene glycol from which to draw a toxicological comparison.” |
Clinical Presentation |
Although the toxicity of propylene glycol is low, if excessively large amounts are absorbed, the following health effects may be seen
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Treatment |
Metabolic acidosis caused by large amounts of propylene glycol in injected medications should be treated with sodium bicarbonate. In severe cases, hemodialysis is effective in correcting hyperosmolality by removing propylene glycol from the blood (Demey, Daelemans et al. 1988; Parker, Fraser et al. 2002). Ethanol therapy, as described for ethylene glycol-poisoned patients, is unnecessary for patients having propylene glycol poisoning. |
Standards and Regulations |
There is no workplace or environmental standard for propylene glycol. FDA considers an average daily dietary intake of 23 mg/kg of body weight to be safe for persons 2-65 years of age (Agency for Toxic Substances and Disease Registry 1997). |
Key Points |
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Progress Check |