POSTED 12 JULY 2007
Diethylene glycol: Not the same as glycerin!
Think a high price makes a lesson more memorable? Then consider the dark and dreary tale of diethylene glycol (DEG), the antifreeze ingredient that has recently shown up in toothpaste -- and in cough syrup that killed scores or more likely hundreds of Panamanians within the past year.
Normally, these products contain a sweet-tasting -- and safe -- solvent called glycerin. But if you mis-label the sweet-tasting DEG as glycerin, you can wind up with a tale of deadly duplicity. On June 1, when the FDA warned about DEG-contaminated Chinese toothpaste, the agency was revisiting a deadly chemical that made headlines 70 years ago.
Headline:The New York Times.
In 1937, sulfa compounds were considered "miracle drugs" because they killed a wide range of harmful bacteria. Then a careless manufacturer dissolved the antibiotic in DEG, slapped on the label "Elixir of Sulfanilamide," and produced a product that killed patients and bacteria both.
Here's how one physician reacted to the sulfanilamide disaster:
"... to realize that six human beings, all of them my patients, one of them my best friend, are dead because they took medicine that I prescribed for them innocently, and to realize that that medicine which I had used for years in such cases suddenly had become a deadly poison in its newest and most modern form ... has given me such days and nights of mental and spiritual agony as I did not believe a human being could undergo and survive" (here's more on the incident.
How could DEG have turned up in a product destined for the human mouth? We asked Gregory Higby, executive director of the American Institute of the History of Pharmacy, who said "you have some chemist who is in charge of putting together a formulation, looking for something that is somewhat sweet that helps dissolve a material in a water-based formulation, and they use diethylene glycol. They taste it, and it is only really poisonous if you take some quantity, it is not cyanide, so they figure there is no problem. The person who did this was not anyone with pharmaceutical or biological training, did not realize they were making a preparation using antifreeze."
Federal law did not require toxicity tests in 1937, but since the term "elixir" describes a solution in ethyl alcohol, not antifreeze, the manufacturer, S.E. Massengill Co., of Bristol, Tenn., was indicted for false labeling. (Ethyl alcohol, ironically enough, is an antidote to DEG poisoning.)
Massengill's chief chemist felt a bit more responsibility than the corporate muckety-mucks, however. He committed suicide. Headlines about the poisoning helped spur passage of the 1938 Federal Food, Drug, and Cosmetic Act, which tightened U.S. drug regulation.
A lesson forgotten
You might think the needless deaths of 105 Americans would be enough to teach a memorable lesson, but diethylene glycol's good side (able solvent, sweet, cheap) has repeatedly overwhelmed those irksome drawbacks (destroys kidneys, kills patients). In 1996 and 1995, for example, 85 Haitian children were killed by a diethylene glycol solution of the pain-reliever acetaminophen.
In 1998, Alan Woolf, now director of environmental medicine at Children's Hospital Boston, compared those poisonings to the hell described in Dante's classic poem The Inferno: "Such a tragedy alone is heart-rending, but within the context of the pharmaceutical history of previous DEG poisonings, it is even more unbearable" (see #5 in the bibliography).
By history, Woolf was alluding to poisonings in Argentina, Bangladesh, Spain, Nigeria, India and South Africa, as well as the sulfanilamide incident. "For unlike the redoubtable poet, who was required to traverse the rings of hell and the plateaus of purgatory only once, we seem to be returning to this dark wood again and again."
We don't often see Dante footnoted in medical journals, so we had to give Woolf a call. We were a bit surprised to learn that he's not all doomy-gloomy about DEG's recurrent popularity. Woolf does not, for example, think the recent poisonings and food-safety issues signify a return to the filthy and frightening conditions in the U.S. meat industry of a century ago. "I do not think we are going back to The Jungle," he says, alluding now to Upton Sinclair's classic muckraking novel of 1906, which sparked passage of the nation's first meaningful food-safety laws. "I have more faith in the professionalism and vigilance of the responsible testing and regulatory agencies than that. Those are extremely isolated incidents, around the world, and are largely excluded from this country. But there is a genuine interest in the safety of the food supply and pharmaceuticals, and this should be a very high priority for all Americans."
The contaminated toothpaste, unlike the deadly Panamanian cough syrup, may pose little danger, Woolf avers, because few people swallow toothpaste. "If it is present in a very low concentration, the medical risk may be negligible. But still, it's quite striking, the contamination of products with compounds which have no business being there." (If you suspect product contamination, Woolf suggests contacting a toxicology expert at the American Association of Poison Control Centers, or phone (800) 222-1222.)
By the 1990s, there was ample evidence that DEG was toxic, and no scrupulous pharmaceutical manufacturer would knowingly use it. The contaminations in Haiti (1996) and Panama (2006) have both been blamed on DEG that was fraudulently labeled "glycerin" in China, before it was shiped abroad and blended into medicine. When the FDA tried to investigate the DEG used in Haiti, its investigators ran into a stone wall: "The Chinese were of little help. Requests to find the manufacturer were ignored. Business records were withheld or destroyed." (See #6 in the bibliography.)
The Centers for Disease Control framed the history more diplomatically: "Complexities in the distribution of glycerin and other pharmaceutical raw materials that may involve many handlers (importers and exporters) underscore the need for manufacturers to adequately identify raw materials and end products."
In other words, Trust, but verify, as Ronald Reagan once said in a different context...
Questions remain. We have not seen reports of civil or legal action against firms that handled the diethylene glycol that wound up in toothpaste, or even Panama's deadly cough syrup. We have not learned the DEG concentration in the toothpaste sold in North America. Chinese toothpaste sold in Japan contained up to 6.2 percent diethylene glycol (see #7 in the bibliography). (In 1937, the toxic antibiotic that killed 105 people contained 72 percent DEG.)
In describing the Haitian chapter of the long saga of diethylene glycol poisoning, Woolf concluded that there was nothing new to learn. "The Haitian epidemic replays all the past folly involved with DEG contamination. There are no new public health lessons from the Haitian tragedy. Rather we simply must be better students of the old lessons..."
The same is true of toxic toothpaste, and deadly cough syrup as well...
Here's another brainstorm: Melamine is perfect for duping protein tests!
Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive