Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds.
Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.
Department of Psychiatry, University of Iowa Carver College of MedicineIowa City, IA, USA; Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Carver College of MedicineIowa City, IA, USA.
Jaymie R
JR
Voorhees
Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Carver College of MedicineIowa City, IA, USA; Department of Occupational and Environmental Health, University of Iowa College of Public HealthIowa City, IA, USA.
Diane S
DS
Rohlman
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis Davis, CA, USA.
Pamela J
PJ
Lein
Department of Psychiatry, University of Iowa Carver College of MedicineIowa City, IA, USA; Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Carver College of MedicineIowa City, IA, USA; Department of Neurology, University of Iowa Carver College of MedicineIowa City, IA, USA; Department of Free Radical and Radiation Biology Program, University of Iowa Carver College of MedicineIowa City, IA, USA; Department of Radiation Oncology Holden Comprehensive Cancer Center, University of Iowa Carver College of MedicineIowa City, IA, USA; Department of Veteran Affairs, University of Iowa Carver College of MedicineIowa City, IA, USA; Weill Cornell Autism Research Program, Weill Cornell Medical CollegeNew York, NY, USA.
Andrew A
AA
Pieper
neurotoxicity; organophosphate ester pesticides; organophosphate pesticides; organophosphates; organophosphorus compounds