title: A multianalyte profile of serum proteins to screen for toxicological effects of anticholinesterase insecticides in the rat.
abstract: The development of high throughput biochemical screens could be useful to assess the broad spectrum of physiological effects of environmental toxicants. To explore the prospect of using a screen in an in vivo exposure scenario, we applied a commercially available multianalyte profile (MAP) of 58 serum biomarkers to rats exposed acutely to two anticholinesterase insecticides, chlorpyrifos (CHP) and carbaryl (CAR). Male, Long-Evans rats were dosed orally with 30 mg/kg CHP, 75 mg/kg CAR or the corn oil vehicle. Doses were selected based on their equivalent physiological effects (hypothermia and reduced motor activity). The animals were terminated 24h or 7 days after dosing. Serum was collected and analyzed for 58 biomarkers consisting primarily of cytokines, chemokines, and a few hormones. There were changes in six analytes (four up, two down) following CHP and eight analytes (five up, three down) following CAR at 24h. There were significant changes in only two biomarkers when measured 7 days after dosing with CHP. Overall, the MAP detected a broad spectrum of unique effects for CHP and CAR. It is concluded that the MAP is a useful tool to screen for in vivo effects of environmental toxicants and its use could lead to the discovery of novel mechanisms of action.
authors.affiliation: Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, MD B105-04, 109 TW Alexander Drive, Research Triangle Park, NC 27711, United States. gordon.christopher@epa.gov
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gordon
authors.forename: William O
authors.initials: WO
authors.lastname: Ward
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis* / Q000187:drug effects*; D012721:Carbaryl / Q000633:toxicity*; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D004390:Chlorpyrifos; D012721:Carbaryl