New Studies to Assess Human Exposures to Pesticides

Pesticide exposure, particularly in children, is a serious health problem in many parts of the world, including the United States.

James Olson, Ph.D., professor of pharmacology and toxicology in the School of Medicine and Biomedical Sciences at the University at Buffalo, is leading research studies on exposure to pesticides, the potential for adverse effects associated with exposures in certain populations and genetic susceptibility to the pesticides. These studies are funded by $1.5 million in new grants from the National Institute of Environmental Health Sciences (NIEHS) and the U.S. Environmental Protection Agency (EPA).

The three-year EPA grant focuses on the activation and detoxification of organophosphate pesticides (OPs), the most commonly used pesticides. OPs can stop the action of acetylcholinesterase, an enzyme essential to nerve function in humans and in other animals and insects.

"One objective of this study is to use experimental data on the rates of activation and detoxification by specific human enzymes and assess the potential for genetic variability in these processes," said Olson. "Levels of pesticide metabolites reported in human urine will be used along with these data to better estimate exposures and the resulting effects of OPs."

The researchers will use an approach called "back-modeling" to better estimate what type of daily human exposure would result in the levels reported in the urine.

"Our mathematical models will help us to estimate doses of the pesticide in specific tissues and the resulting inhibition of acetylcholinesterase, a key enzyme that inactivates neurotransmitters," said Olson.

"Together, these results will provide better estimates of what levels of exposure to a pesticide may be 'safe' and what would be harmful."

The University at Buffalo is collaborating with Oregon Health and Sciences University, the University of Washington, and Egypt's Menoufia University on the four-year NIEHS grant. The researchers will assess exposures to OP pesticides in 255 Egyptian cotton field workers and determine if there are neurotoxic effects.

They hypothesize that neurobehavioral deficits induced by OP exposure are dose-related, and that oxidative stress and inflammation are better measures of deficits than inhibition of acetylcholinesterase.

"These [University at Buffalo] studies will provide data necessary to develop biomarkers of OP exposure, biologic response, and genetic susceptibility," said Olson. "Having markers will help identify people at risk and make it easier to test the usefulness of interventions and treatments.

"This information is important because OPs are used widely throughout the world, and they are potential chemical agents of terrorism."

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