Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

Details

• Personal Author:
  Busby AL ; Lee, Stephen A. ; Poet TS ; Timchalk C
• Description:
  The routine use of tobacco products may modify key metabolizing systems, which will further impact the metabolism of environmental contaminants. The objective of this study was to quantify the effect of repeated in vivo exposures to nicotine, a major pharmacologically active component of cigarette smoke, on in vitro metabolism of chlorpyrifos (CPF). CPF is an organophosphorus (OP) insecticide that is metabolized by cytochrome P-450 (CYP450) to its major metabolites, chlorpyrifos-oxon (CPF-oxon) and 3,5,6-trichloro-2-pyridinol (TCP). Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg for 1, 7, or 10 d. Rats were sacrificed 4 or 24 h after the last nicotine treatment, and liver microsomes were prepared. The microsomes were incubated with varying concentrations of CPF and the production of the metabolites CPF-oxon and TCP were measured. The metabolism of CPF to the active oxon metabolite did not show significant changes following repeated nicotine treatments, evidenced by the unchanged pseudo first-order clearance rate of V(max)/K(mapp). The V(max) describing the metabolism of CPF to the inactive metabolite, TCP was increased in 24-h postdosing groups, after both single and repeated treatments of nicotine. In contrast, the metabolism to TCP was unchanged in groups evaluated at 4 h (single or repeated) post nicotine dosing. Some basic marker substrate activities were also investigated to ensure that nicotine exerted effects on CYP450 activities. Total P450 reduced spectra were not altered by nicotine treatment, but marker substrate activities for CYP1A and CYP2E1 were increased at 24 h after the single treatment, and marker substrate activity for CYP2B was decreased 4 h after 7 d of treatment. Results of this in vitro study suggest that repeated nicotine exposure may result in altered metabolism of CPF. Future in vivo experiments based on these results need to be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Environmental Exposure Insecticides Laboratories Occupational Health Organophosphates Safety
• Keywords:
  Environmental-exposure In-vitro-studies Laboratory-animals Laboratory-testing Metabolic-study Organo-phosphorus-compounds Organo-phosphorus-pesticides Pesticides Pesticides-and-agricultural-chemicals
• ISSN:
  1528-7394
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  74-82
• Volume:
  72
• Issue:
  2
• NIOSHTIC Number:
  nn:20034970
• Citation:
  J Toxicol Environ Health A 2009 Jan; 72(2):74-82
• Contact Point Address:
  T. S. Poet, Center for Biological Monitoring and Modeling, Pacific Northwest National Laboratory, 902 Battelle Blvd, PO Box 999, MSIN: P7-59, Richland, WA 99352
• Email:
  torka.poet@pnl.gov
• CAS Registry Number:
  Chlorpyrifos (CAS RN 2921-88-2) ; Diazinon (CAS RN 333-41-5) ; Lead (CAS RN 7439-92-1)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods
• 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-512:0a6adfb754d3adab9f35aa718b14ce81bf5b7b39aad56dd120c292969dc18581113d0faec4df1d6d96d5814c1f14f0ab287eb2841b2b9ae9349cb4693acf46c0
• Download URL:
  https://stacks.cdc.gov/view/cdc/186977/cdc_186977_DS1.pdf
• File Type:
  [PDF - 778.97 KB ]