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A number of studies, dating back to 1980, suggest that propylene glycol may be damaging to the kidneys. In 1994, scientists at the Louisiana State University Medical Center reported that propylene glycol in concentrations as low as 0.5 percent can be toxic to cultured kidney cells and that its use as a drug solvent could accelerate the damage. Like the British in 1987, the LSU researchers recommended that manufacturers exercise caution in using propylene glycol as a drug-delivery device.
Likewise, a team of German scientists recommended that propylene glycol be replaced as a solvent in drugs after finding that concentrations of the substance in the bloodstream actually increase over time. They recommend diluting propylene glycol in saline "to minimize the undesirable effects of this solvent."
To put these studies, which evaluate the effects of relatively low levels of propylene glycol, into the proper context, consider a 1993 report from the University of Missouri-Kansas City. Researchers there administered over-the-counter Dramamine --which is 50 percent propylene glycol -- to female rabbits, and found that the solvent significantly reduced the rabbits' ability to metabolize, or process and eliminate, the active ingredient.
Wayne Snodgrass says the FDA and drug manufacturers need to examine more closely the kinetics of propylene glycol -- in other words, how it is handled by the human body. Snodgrass says that alcohol has "zero-order kinetics," which means that each subsequent dose may increase the concentration in the bloodstream three, four or even five times.
"At some point, any substance will build up, but the question of propylene glycol is, when does it happen?" Snodgrass says. "What is the dose that generates that effect in the general population? If you're a public-health official, you have to ask, 'What is the safety factor so the general population can have some dose, but not any more?'
"Well, there are no controlled, random studies in humans, so to do that, you have to go on what you know from animal studies."
The most significant animal study on propylene glycol actually led the FDA to ban the substance in cat foods in 1996. Once again, the federal agency was well behind the scientific curve. In 1976, 20 years earlier, researchers in Europe reported that propylene glycol increased the presence of Heinz bodies in cat hemoglobin, an indication of red blood cell damage. Those results led to the formation of a group of pet-food researchers in the U.S., who found that, in addition to the damage propylene glycol causes to red blood cells, the substance accumulates in the liver and causes heart and kidney lesions in cats.
After the U.S. research was published in 1994, the FDA took only two years to pull propylene glycol's status as a substance "generally regarded as safe," or GRAS, and ban it from cat food. Compare that to the ten- or 12-year lag in how the FDA reacted to the documented dangers of ethanol, and it's little wonder that, as time goes by, Mark Wilson is increasingly worried about propylene glycol's continued use in children's medications.
"I think the FDA ought to consider its own history," he says. "The original incident that strengthened the Food and Drug Act happened in 1938 --about a hundred people died after they were poisoned by ethanol that had been used as a solvent in cough and cold medicine. Now here we are, 60 years later...."
After almost eight years of inaction by the federal agency, Wilson took his crusade to Capitol Hill. In a long, pointed letter to U.S. Senator Phil Gramm of Texas, he expressed frustration at the FDA's lack of response, not only to Wilson's repeated inquiries about propylene glycol, but to the troubling scientific data on the substance. He asked Gramm to contact the FDA to see if a U.S. senator could get an answer.
It took two letters from Gramm's office over a six-month period to finally get a response from the agency in late February. The four-page letter from an FDA legislative liaison is interesting because it's really the first defense the agency has offered for the use of propylene glycol, to Wilson or anyone else.
According to the FDA, the substance has been in use in drugs for more than 50 years and in foods since at least 1920. Its GRAS status dates back to 1959. The FDA also notes that propylene glycol, in addition to its ability to dissolve active ingredients, is effective as a solvent and "plasticizing agent" in food.
But, as to why propylene glycol is not classified as an alcohol, the FDA's explanation is less than compelling: "Although propylene glycol is, as a matter of scientific nomenclature, a member of the class of hydroxyl compounds identified as alcohols, propylene glycol is not alcohol as the word is commonly understood. As commonly understood, 'alcohol' means ethyl alcohol, i.e., the type found in alcoholic beverages."
Presumably, the job of a watchdog organization like the FDA is to help distinguish what is "commonly understood" from what people don't know, but probably should. Just as questionable is the FDA's assertion that it has "considered the available body of evidence, and concluded that, in the amounts that propylene glycol is commonly used in drug products, the chemical poses no unacceptable risks."