Metabolic Interactions of Agrochemicals in Humans

Details

• Personal Author:
  Hodgson E ; Rose RL
• Description:
  Agrochemicals and other xenobiotics are metabolized by xenobiotic-metabolizing enzymes (XMEs) to products that may be more or less toxic than the parent chemical. In this regard, phase-I XMEs such as cytochrome P450s (CYPs) are of primary importance. Interactions at the level of metabolism may take place via either inhibition or induction of XMEs. Such interactions have often been investigated, in vitro, in experimental animals, using subcellular fractions such as liver microsomes, but seldom in humans or at the level of individual XME isoforms. The authors have been investigating the metabolism of a number of agrochemicals by human liver microsomes and recombinant CYP isoforms and have recently embarked on studies of the induction of XMEs in human hepatocytes. The insecticides chlorpyrifos, carbaryl, carbofuran and fipronil, as well as the repellant DEET, are all extensively metabolized by human liver microsomes and, although a number of CYP isoforms may be involved, CYP2B6 and CYP3A4 are usually the most important. Permethrin is hydrolyzed by esterase(s) present in both human liver microsomes and cytosol. A number of metabolic interactions have been observed. Chlorpyrifos and other phosphorothioates are potent inhibitors of the CYP-dependent metabolism of both endogenous substrates, such as testosterone and estradiol, and exogenous substrates, such as carbaryl, presumably as a result of the interaction of highly reactive sulfur, released during the oxidative desulfuration reaction, with the heme iron of CYP. The hydrolysis of permethrin in human liver can be inhibited by chlorpyrifos oxon and by carbaryl. Fipronil can inhibit testosterone metabolism by CYP3A4 and is an effective inducer of CYP isoforms in human hepatocytes. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Insecticides Occupational Health Safety
• Keywords:
  Author Keywords: Cytochrome P450 Environmental Chemicals Hepatocytes Human Metabolism Humans Liver Cells Metabolic Effects Metabolism Organophosphorus Chemicals Organophosphorus Compounds Pesticides And Agricultural Chemicals Risk Assessment Xenobiotics

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• ISSN:
  1526-498X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  64
• Issue:
  6
• NIOSHTIC Number:
  nn:20062093
• Citation:
  Pest Manag Sci 2008 Jun; 64(6):617-621
• Contact Point Address:
  Ernest Hodgson, Department of Environmental and Molecular Toxicology, Campus Box 7633, North Carolina State University, Raleigh, NC 27695-7633, USA
• Email:
  ernest_hodgson@ncsu.edu
• CAS Registry Number:
  Carbaryl (CAS RN 63-25-2) ; Carbofuran (CAS RN 1563-66-2) ; Chlorpyrifos (CAS RN 2921-88-2) ; Fipronil (CAS RN 120068-37-3) ; N,N-Diethyl-m-toluamide (CAS RN 134-62-3)
• Federal Fiscal Year:
  2008
• Performing Organization:
  East Carolina University
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Pest Management Science
• End Date:
  20080929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2dfa526de731871a1e33dd7aeecdfcbf007f76ac926cd6e0b9c0fd8eea91cf6d2677251e46a83e5feff4171d3e7080b468c7142443faf3418179c353255fa8f2
• Download URL:
  https://stacks.cdc.gov/view/cdc/225406/cdc_225406_DS1.pdf
• File Type:
  [PDF - 90.36 KB ]