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Research Magazine > ARCHIVE > Spring 92 > Article

Predicting the Effects of Toxic Chemicals
by Sheila Roberson

Chemicals may be taking us to the cleaners.

Dry cleaning solvents, for instance, often show up in our air and water, a result of widespread leaks of chemical wastes. Even their fumes evaporate from dry-cleaned clothing and seep into the air we breathe.

And they cost us more than mere money. They spoil the environment and pose potential danger to our health.

That's why Dr. Cham Dallas is using the main agent employed in dry cleaning solvents in his study on the risks people face from exposure to chemicals.

Dallas, a toxicologist in the UGA College of Pharmacy, is working with two of the most widespread pollutants in the world to develop computer models of how chemicals interact with the body.

If successful, his computer simulations will help scientists predict the effects of chemical exposure and accurately diagnose the amount of exposure a person has received. They may even reduce the number of laboratory animals used in future experiments to determine the consequences of chemical contamination.

"Specifically, we're looking at chemicals that evaporate easily into the air around us," Dallas said. "If they escape from tanks or pipes at an industrial site, they can contaminate the air we breathe or seep into the ground and pollute our drinking water."

To determine the risk to humans, Dallas first studies the effects of these chemicals on animals. He then uses these results to verify his computer simulations.

"We use computer simulation models designed to predict the chemicals' effects on the animals. We then check the accuracy of the models by comparing the predictions with what actually happens in the animals' tissues when the chemicals are given," he said. "Eventually we hope to use the computer simulation models to predict how these and other chemicals might affect man."

The chemicals Dallas and his research team work with are among the most prevalent contaminants in the environment. Dry cleaning fluid is known as perchloroethylene among chemists and dry cleaners; tetrachloroethane is a chemical intermediate in the manufacture of many industrial chemicals.

"Like the flour used in baking, these chemicals are the building blocks for many other chemical compounds. They can be found in everything from plastic cups to carpet and office furniture," Dallas said.

They were also selected for the research because there are wide differences in their physicochemical properties.

"We chose these chemicals because we wanted a good test for our computer models," he said. "If the computer models make accurate predictions for kinetics and toxicity for both agents, we know the models are very robust. If not, then we will have greater confidence that the weakness in the model could be due to an inability to predict a certain physiochemical property. We can then evaluate additional chemicals on that basis."

European studies conducted in the 1970s in humans showed that perchloroethylene affects judgment, coordination, thinking and reasoning. It also can cause headaches, dizziness and even unconsciousness, Dallas said.

Perchloroethylene and terrachloroethane both depress activity of the central nervous system, which relays messages to and from the brain to all other parts of the body. Symptoms range from mild to serious, depending on the level of exposure. Perchloroethylene also is implicated as a carcinogen in some studies.

Using the results of these early tests as a base line, Dallas conducted a four-year study, funded by the Air Force, to determine the effects of several volatile chemicals in animal models. He assessed chemical concentration and elimination over time in the brain, lung, liver, kidney, fat, blood, muscle, heart and exhaled breath. With the help of Dr. James Gallo in the College's department of pharmaceutics, he compared the data with computer simulation models.

"The primary consideration of the first study was to develop a model that could accurately predict chemical levels in animal models. If the animal studies failed to validate our existing computer model, we had to see where our model was wrong," he said. "For example, if the computer model inaccurately predicted the levels of chemical in the liver, the problem may have been due to an incorrect prediction of metabolism in the liver. I have published several papers demonstrating a high degree of accuracy in the ability of the models to predict correctly the levels of halocarbon chemicals in animals."

The second phase of the study, funded by a three-year grant from the Department of Defense, includes determining toxicity at different levels of exposure. Doctoral student Alan Warren tests the animals to see how their behavior is affected by certain levels of chemicals in the brain.

In these tests, a computer sets a task for the animal to perform and gives food as a reward. As toxicity increases, the animal's performance is either depressed or excited, depending on the chemical.

"By knowing the level of chemical that the animal is exposed to and by using the computer simulation model to correctly predict the level of the chemical that will appear in the brain, we can define what toxicity will result from that exposure level," Dallas said.

"The computer model could also be used in reverse. We could look at the symptoms and/or the brain concentration levels and predict what exposure level was needed to create those results," he said.

If Dallas' computer simulation models correctly predict the physiological effects of these chemicals between lab animals and man, then toxicologists will have more confidence that similar models will be useful in extrapolating the effects of other chemicals from animal species to man.

"The government wants to be able to set limitations on chemical exposure in order to protect public health and the environment," he said. "At some point in the future, this may mean that computer simulation models could reduce the need for animal studies."

Dallas has received grants as Principal Investigator totalling $847,000 from agencies within the U.S. Department of Defense to fund continuous the toxicity studies for over a seven year period.

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