In vitro interactions between organophosporous pesticides and consequences of pre-treatment with nicotine and alcohol on in vitro pesticide metabolism in rats.

Details

• Personal Author:
  Kousba A ; Poet TS ; Timchalk C ; Zangar RC
• Description:
  Chlorpyrifos (CPF) and diazinon (DZN) are structurally and mechanistically similar pesticides, having different rates of metabolism. Their toxicity is mediated through CYP450 metabolism to CPF-oxon and DZN-oxon. Detoxification is also mediated by CYP450s, forming a pyridinol (TCP) and a pyrimidine (IMHP), respectively. Since exposures to pesticides may be complicated by exposure to multiple pesticides and other xenobiotics, the effect of co-incubation of CPF and DZN on the in vitro metabolism of each pesticide was assessed, as was the effect of pre-treating rats with nicotine or ethanol for 5 days. Western blot analysis of several CYP450 proteins indicated no induction as a result of nicotine treatment and a slight induction due to ethanol pre-treatment. Interestingly, co-incubation with two pesticides or pre-treatment with nicotine or ethanol had different effects on bioactivation and detoxification pathways. There was little effect on TCP formation following either pre-treatment, but a potential slight induction of oxon following nicotine pre-treatment. Detoxification of the parent pesticides was inhibited in a competitive manner by co-incubation, whereas bioactivation to the oxons indicated a non-competitive mechanism. Inhibitory rate constants were approximately 5-fold higher for the bioactivation pathways than the detoxification pathways. Metabolic interactions between pesticides and as a result of nicotine or alcohol exposures are potentially very important to the ratio of bioactivation/detoxification of these compounds in vivo. [Description provided by NIOSH]
• Subjects:
  Agriculture Energy Metabolism Insecticides Occupational Health Safety
• Keywords:
  Pesticides; Pesticides-and-agricultural-chemicals; Pesticide-residues; Pest-control; Insecticides; Insecticide-poisoning; Metabolic-study; Metabolism; Metabolites; Agricultural-chemicals; Agricultural-industry; Agriculture
• ISSN:
  0360-2532
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Proceedings ; Abstract
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  36
• NIOSHTIC Number:
  nn:20026149
• Citation:
  Drug Metab Rev 2004 Sep; 36(Suppl 1):536
• Contact Point Address:
  Battelle, Pacific Northwest Division, 999 Battelle Blvd., Richland WA
• CAS Registry Number:
  Chlorpyrifos (CAS RN 2921-88-2) ; Diazinon (CAS RN 333-41-5)
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods
• Performing Organization:
  Battelle Memorial Institute, Richland, Washington
• Peer Reviewed:
  False
• Start Date:
  20010930
• Source Full Name:
  Drug Metabolism Reviews
• Supplement:
  1
• End Date:
  20050929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/247977/cdc_247977_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]