UB Receives $1.5 Million to Assess Human Exposures to Pesticides and Associated Adverse Effects

BUFFALO, N.Y. -- Pesticide exposure, particularly in children, is a serious health problem in many parts of the world, including the U.S.

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.

The studies are funded by $1.5 million in new grants from the National Institute of Environmental Health Sciences (NIEHS) and the Environmental Protection Agency (EPA).

The three-year EPA grant focuses on the activation and detoxification of organophosphate pesticides (OPs), the most commonly used pesticides in the U.S. and worldwide. 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."

UB 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.

Olson said it has been difficult to predict the risk of exposure to OP in humans because the relationship of OP doses to neurobehavioral deficits hasn't been well established in humans. In addition, there are no reliable biomarkers to predict deficits, he said, and the potential for genetic variation to modify sensitivity to exposure hasn't been investigated thoroughly.

UB will lead studies assessing human exposure to these pesticides in the study population, carry out pharmacokinetic and pharmacodynamic modeling of pesticide exposure and effect, and investigate the potential of genetic variability of drug-metabolizing enzymes to modify biomarkers of exposure and effect.

"These 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."

Matthew Bonner, Ph.D., from the UB School of Public Health and Health Professions' Department of Social and Preventive Medicine, and James Knaak, Ph.D., from the UB Department of Pharmacology and Toxicology, are co-investigators on the UB portion of both grants.

UB co-investigators on the EPA grant are Aiming Yu, Ph.D., from the School of Pharmacy and Pharmaceutical Sciences; Richard Browne, Ph.D., from the Department of Biotechnology and Clinical Laboratory Sciences, and Paul Kostyniak, Ph.D., from the Department of Pharmacology and Toxicology, both in the UB School of Medicine and Biomedical Sciences.

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system that is its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.