title: Experimental strategy for translational studies of organophosphorus pesticide neurotoxicity based on real-world occupational exposures to chlorpyrifos.
abstract: Translational research is needed to understand and predict the neurotoxic consequences associated with repeated occupational exposures to organophosphorus pesticides (OPs). In this report, we describe a research strategy for identifying biomarkers of OP neurotoxicity, and we characterize pesticide application workers in Egypt's Menoufia Governorate who serve as our anchor human population for developing a parallel animal model with similar exposures and behavioral deficits and for examining the influence of human polymorphisms in cytochrome P450 (CYP) and paraoxonase 1 (PON1) enzymes on OP metabolism and toxicity. This population has previously been shown to have high occupational exposures and to exhibit a broad range of neurobehavioral deficits. In addition to observational studies of work practices in the field, questionnaires on demographics, lifestyle and work practices were administered to 146 Egyptian pesticide application workers applying pesticides to the cotton crop. Survey results indicated that the application workforce uses standard operating procedures and standardized equipment provided by Egypt's Ministry of Agriculture, which provides a workforce with a stable work history. We also found that few workers report using personal protective equipment (PPE), which likely contributes to the relatively high exposures reported in these application workers. In summary, this population provides a unique opportunity for identifying biomarkers of OP-induced neurotoxicity associated with occupational exposure.
authors.affiliation: Department of Molecular Biosciences, UC Davis School of Veterinary Medicine, Davis, CA 95618, USA. pjlein@ucdavis.edu
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Bonner
authors.forename: Fayssal M
authors.initials: FM
authors.lastname: Farahat
authors.forename: James R
authors.initials: JR
authors.lastname: Olson
authors.forename: Diane S
authors.initials: DS
authors.lastname: Rohlman
authors.forename: Richard A
authors.initials: RA
authors.lastname: Fenske
authors.forename: K Matthew
authors.initials: KM
authors.lastname: Lattal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lasarev
authors.forename: Kit
authors.initials: K
authors.lastname: Galvin
authors.forename: Taghreed M
authors.initials: TM
authors.lastname: Farahat
authors.forename: W Kent
authors.initials: WK
authors.lastname: Anger
mesh_terms: D000293:Adolescent; D000328:Adult; D000382:Agricultural Workers' Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control; D000383:Agriculture; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D004390:Chlorpyrifos / Q000009:adverse effects* / Q000378:metabolism; D004534:Egypt; D006801:Humans; D007306:Insecticides / Q000009:adverse effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D009483:Neuropsychological Tests; D009488:Neurosciences / Q000379:methods*; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D016273:Occupational Exposure / Q000009:adverse effects* / Q000517:prevention & control; D062025:Organophosphate Poisoning / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D011482:Protective Devices; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014116:Toxicology / Q000379:methods*; D057170:Translational Research, Biomedical; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007306:Insecticides; D004390:Chlorpyrifos