Nav: Home

Dangerous Chemical Combination Presents Possible Scenario For Gulf War Illnesses

April 29, 1996

WASHINGTON -- Animal experiments at Duke University Medical Center show that harmless doses of three chemicals used to protect Gulf War soldiers from insect-borne diseases and nerve-gas poisoning are highly toxic when used in combination, researchers reported Wednesday. They said the findings may explain the wide array of symptoms reported by an estimated 30,000 Gulf War veterans.

In studies using chickens, the researchers specifically found that two pesticides, DEET and permethrin, and the anti-nerve gas agent pyridostigmine bromide (PB) were harmless when used alone, even at three times the doses soldiers likely received. But when used in combination, the chemicals caused neurological deficits in the test animals similar to those reported by some Gulf War veterans, according to Duke pharmacologist Mohamed Abou-Donia and Tom Kurt, a toxicologist at The University of Texas Southwestern Medical Center in Dallas.

Chickens were selected over rodents as test animals because their susceptibility to neurotoxic chemicals more closely resembles that of humans, the scientists said.

The findings were prepared for presentation Wednesday at the annual meeting of the Federation of American Societies for Experimental Biology and will be published in the May issue of the Journal of Toxicology and Environmental Health.

The researchers said their findings are similar to those reported in Scotland last month and by an Israeli team last year.

Adding to those findings, the Duke and UT Southwestern scientists have developed a theory to explain why the chemical mix is dangerous. They said their results indicate the anti-nerve gas agent reduces the body's normal ability to inactivate the two pesticides, which can then travel to and damage the brain and nervous system. Such a mechanism could explain the wide array of symptoms reported by some Gulf War veterans, including memory loss, headache, fatigue, muscle and joint pain, weakness, shortness of breath and tremors, the researchers said.

"The decision to use these chemicals was made to protect soldiers from indigenous diseases in the gulf, such as malaria and leishmaniasis," said Abou-Donia, lead investigator of the study. "Without protection, there may have been thousands of deaths. But it appears that, for some veterans, the precautions prevented one set of problems and created another. Now, our task is to analyze the veterans' symptoms by investigating all the potential causes, not only for their sakes but for the welfare of future soldiers."

The Duke study is one of a three-part investigation on Gulf War illnesses organized by UT Southwestern. Co-authors of the Duke study include former Duke researcher Kenneth R. Wilmarth, now at ENVIRON Corp. in Arlington, Va.; Kurt; Karl F. Jensen of the Environmental Protection Agency at Research Triangle Park, N.C.; and Frederick W. Oehme of Kansas State University.

"Together, the three phases of our investigation may solve the mystery of some Gulf War veterans' illnesses," Kurt said. "The animal studies are an important component because they test the biological plausibility of our theory that combinations of certain chemicals can cause symptoms that are not caused by individual chemicals alone."

In the Duke study, researchers exposed healthy chickens to each of the three chemicals -- DEET, permethrin and PB -- individually and then in various combinations.

Doses of each chemical were selected prior to the study by determining the maximum amount a chicken could withstand without showing clinical signs -- a dose representing at least three times the amount soldiers likely received. DEET and permethrin were administered subcutaneously and PB was given orally.

"Even if a person was exposed to one chemical alone at three times the recommended dose, he or she would have remained healthy," Abou-Donia said. "Our first task was to demonstrate the safety of each chemical when used individually."

The chickens exposed to individual chemicals showed no outward signs of illness or debilitation, the researchers said. But chickens exposed to any two chemical combinations exhibited varying degrees of weight loss, diarrhea, shortness of breath, decreased activity, stumbling, leg weakness and a reluctance to walk, impaired flying or tremors. The combination of all three chemicals produced the most severe signs, resulting in total paralysis or death in some chickens.

A laboratory analysis of tissues in the central and peripheral nervous systems showed that multiple chemical exposure caused enlarged axons and axonal degeneration, a sign of widespread nervous system damage.

Tests also suggested that the severity of clinical signs depends on how active a particular blood enzyme is in removing the foreign chemicals from the body, the researchers said. This "scavenger" enzyme, called plasma butyrylcholinesterase (BuChE), inactivates foreign chemicals such as DEET and permethrin.

However, the scientists said there is a finite and limited amount of BuChE in the bloodstream, enough to neutralize DEET alone or permethrin alone. When multiple chemicals are present, the enzyme is unable to neutralize them all, resulting in a toxic accumulation of chemicals in the bloodstream and thus in the brain and nervous system.

Moreover, the anti-nerve gas agent PB further inhibits the action of this scavenger enzyme, BuChE. While PB's intended purpose is to temporarily shield and protect another similar enzyme, acetylcholine esterase (AChE), from nerve gas damage, it cannot distinguish between AChE and BuChE and therefore binds to both, the researchers said. So, even less BuChE is available to combat and neutralize DEET and permethrin.

"Pyridostigmine bromide actually pumps more of the other chemicals to the brain," said Abou-Donia. "While PB itself cannot cross the blood-brain barrier, it magnifies the effects of the other two chemicals by tying up the available BuChE."

Abou-Donia said an additional genetic risk factor arises in some individuals who have a faulty form of BuChE, resulting in low enzymatic activity and thus a diminished ability to inactivate drugs or pesticides. This risk factor, which affects only 3 to 4 percent of the population, may boost the toxicity of these chemicals.

"Individuals with genetic types of decreased plasma BuChe activity should be considered potentially at higher risk when exposed to PB and related compounds, and this may account for some of the more severe symptoms seen in up to 4 percent of the Gulf War veterans," said Abou-Donia. An estimated 700,000 military personnel served in the Gulf War.

In addition, soldiers who took higher-than-recommended doses of PB as an added precaution against nerve gas attacks may have caused nerve-cell overstimulation, contributing to tremors, muscle spasms and other symptoms of increased nerve-cell activity.

The research team is conducting a follow-up study analyzing blood samples from veterans with and without symptoms to determine if low enzymatic activity is associated with signs of illness.


###




Duke University

Related Nervous System Articles:

Fewer scars in the central nervous system
Researchers have discovered the influence of the coagulation factor fibrinogen on the damaged brain.
Polymerized estrogen shown to protect nervous system cells
In research published today in Nature Communications, an interdisciplinary team from Rensselaer Polytechnic Institute demonstrated how estrogen -- a natural hormone produced in the body -- can be polymerized into a slow-releasing biomaterial and applied to nervous system cells to protect those cells and even promote regeneration.
Discovery concerning the nervous system overturns a previous theory
It appears that when our nervous system is developing, only the most viable neurons survive, while immature neurons are weeded out and die.
Autonomic nervous system appears to function well regardless of mode of childbirth
'In a low-risk group of babies born full-term, the autonomic nervous system and cortical systems appear to function well regardless of whether infants were exposed to labor prior to birth,' says Sarah B.
First step to induce self-repair in the central nervous system
Injured axons instruct Schwann cells to build specialized actin spheres to break down and remove axon fragments, thereby starting the regeneration process.
First complete wiring diagram of an animal's nervous system
In a study published online today in Nature, researchers at Albert Einstein College of Medicine describe the first complete wiring diagram of the nervous system of an animal, the roundworm Caenorhabditis elegans, used by scientists worldwide as a model organism.
Scientists unlock new role for nervous system in regeneration
Biologists have developed a computational model of flatworm regeneration to answer an important question in regeneration research - what are the signals that determine the rebuilding of specific anatomical structures?
Research gives new insight into the evolution of the nervous system
Pioneering research has given a fascinating fresh insight into how animal nervous systems evolved from simple structures to become the complex network transmitting signals between different parts of the body.
Researchers solve mystery of how ALL enters the central nervous system
A research team led by Duke Cancer Institute scientists has found that this blood cancer infiltrates the central nervous system not by breaching the blood-brain barrier, but by evading the barrier altogether.
The VIPs of the nervous system
Biologists at Washington University in St Louis unlocked a cure for jet lag in mice by activating a small subset of the neurons involved in setting daily rhythms.
More Nervous System News and Nervous System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.