Impact of repeated nicotine and alcohol coexposure on in vitro and in vivo chlorpyrifos dosimetry and cholinesterase inhibition

Details

• Personal Author:
  Gunawan R ; Hjerpe AL ; Lee, Stephen A. ; Poet TS ; Smith JN ; Timchalk C
• Description:
  Chlorpyrifos (CPF) is an organophosphorus insecticide, and neurotoxicity results from inhibition of acetylcholinesterase (AChE) by its metabolite, chlorpyrifos-oxon. Routine consumption of alcohol and tobacco modifies metabolic and physiological processes impacting the metabolism and pharmacokinetics of other xenobiotics, including pesticides. This study evaluated the influence of repeated ethanol and nicotine coexposure on in vivo CPF dosimetry and cholinesterase (ChE) response (ChE- includes AChE and/or butyrylcholinesterase (BuChE)). Hepatic microsomes were prepared from groups of naive, ethanol-only (1 g/kg/d, 7 d, po), and ethanol + nicotine (1 mg/kg/d 7 d, sc)-treated rats, and the in vitro metabolism of CPF was evaluated. For in vivo studies, rats were treated with saline or ethanol (1 g/kg/d, po) + nicotine (1 mg/kg/d, sc) in addition to CPF (1 or 5 mg/kg/d, po) for 7 d. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), in blood and urine and the plasma ChE and brain acetylcholinesterase (AChE) activities were measured in rats. There were differences in pharmacokinetics, with higher TCPy peak concentrations and increased blood TCPy AUC in ethanol + nicotine groups compared to CPF only (approximately 1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain AChE activities after ethanol + nicotine treatments showed significantly less inhibition following repeated 5 mg CPF/kg dosing compared to CPF only (96 +/- 13 and 66 +/- 7% of naive at 4 h post last CPF dosing, respectively). Although brain AChE activity was minimal inhibited for the 1-mg CPF/kg/d groups, the ethanol + nicotine pretreatment resulted in a similar trend (i.e., slightly less inhibition). No marked differences were observed in plasma ChE activities due to the alcohol + nicotine treatments. In vitro, CPF metabolism was not markedly affected by repeated ethanol or both ethanol + nicotine exposures. Compared with a previous study of nicotine and CPF exposure, there were no apparent additional exacerbating effects due to ethanol coexposure. [Description provided by NIOSH]
• Subjects:
  Animals Cholinesterase Inhibitors Energy Metabolism Environmental Monitoring Ethanol Insecticides Laboratories Nervous System Occupational Health Organophosphates Safety

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• Keywords:
  Acetylcholinesterase Animal-studies Brain-function Cholinesterase-inhibitors Dose-response Ethanols Exposure-assessment In-vitro-studies In-vivo-studies Laboratory-animals Laboratory-testing Metabolites Neurotoxic-effects Neurotoxins Organo-phosphorus-compounds Organo-phosphorus-pesticides Pharmacodynamics

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• ISSN:
  1528-7394
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; OSHA Region 10 ; OSHA Region 4 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  74
• Issue:
  20
• NIOSHTIC Number:
  nn:20039860
• Citation:
  J Toxicol Environ Health A 2011 Oct; 74(20):1334-1350
• Contact Point Address:
  C. Timchalk, Biological Monitoring and Modeling, Pacific Northwest National Laboratory, 902 Battelle Blvd, PO Box 999, MSIN: P7-59, Richland, WA 99352, USA
• Email:
  Charles.timchalk@pnl.gov
• CAS Registry Number:
  (-)-Nicotine (CAS RN 54-11-5) ; 3,5,6-Trichloro-2-pyridinol (CAS RN 6515-38-4) ; Chlorpyrifos (CAS RN 2921-88-2) ; Chlorpyrifos oxon (CAS RN 5598-15-2) ; Ethanol (CAS RN 64-17-5)
• Federal Fiscal Year:
  2012
• Performing Organization:
  Battelle Memorial Institute, Richland, Washington
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Journal of Toxicology and Environmental Health, Part A: Current Issues
• End Date:
  20050929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7ac6881a0df7e9d8c0b846506b9291f37e5da0e0eed0c826099e7d226db21cb86952e1405ca39885addc8a21d295351a36093cfbfd7740bc6c1e42071e158b9c
• Download URL:
  https://stacks.cdc.gov/view/cdc/192926/cdc_192926_DS1.pdf
• File Type:
  [PDF - 1000.15 KB ]