In vitro metabolism study of carbofuran and its metabolic interaction with testosterone.

Details

• Personal Author:
  Hodgson E ; Rose RL ; Usmani KA
• Description:
  Carbofuran is a widely used carbamate pesticide in agricultural practice throughout the world. Its effect as a pesticide is due to its ability to inhibit acetylcholinesterase activity. This study was designed to investigate the in vitro human and rodent metabolism of carbofuran, human cytochrome P450 (CYP) isoforms, and possible interactions with testosterone. Carbofuran is metabolized by CYPs leading to the production of a major ring oxidation metabolite, 3-hydroxycarbofuran, and two minor metabolites. Pooled HLM have a significantly higher Km value (1950 µM) than RLM Km (210 microM) and MLM Km (550 microM) and intrinsic clearance rate calculations indicate that HLM metabolize carbofuran to 3-hydroxycarbofuran almost 14-folds lower than RLM and MLM. Differences between rat and human are due to rat CYP2Cs. Among 16 human cDNA-expressed CYP enzymes examined, CYP3A4 was the major isoform responsible for carbofuran metabolism to 3-hydroxycarbofuran. Use of phenotyped HLM demonstrated that the variation in carbofuran metabolism among 17 single-donor HLM samples is over 5-fold and the best correlation between CYP isoform activity and carbofuran metabolism was observed with CYP3A4. The interaction of carbofuran with an endogenous CYP3A4 substrate, testosterone (TST), was investigated. TST metabolism was activated by carbofuran in HLM and CYP3A4, however, less activation was observed for carbofuran metabolism by TST in HLM and CYP3A4. [Description provided by NIOSH]
• Subjects:
  Agriculture Energy Metabolism Insecticides Occupational Health Safety
• Keywords:
  Pesticides; Pesticides-and-agricultural-chemicals; Pesticide-residues; Agricultural-chemicals; Agricultural-industry; Agriculture; In-vitro-study; Metabolic-study; Insecticides
• ISSN:
  0360-2532
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Abstract or Summary
• 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:
  36
• NIOSHTIC Number:
  nn:20026148
• Citation:
  Drug Metab Rev 2004 Sep; 36(Suppl 1):534
• Contact Point Address:
  Department of Environmental and Molecular Toxicology, Box 7633, North Carolina State University, Raleigh, NC 27695
• CAS Registry Number:
  Carbofuran (CAS RN 1563-66-2)
• Federal Fiscal Year:
  2004
• Performing Organization:
  East Carolina University
• Peer Reviewed:
  False
• Start Date:
  20010930
• Source Full Name:
  Drug Metabolism Reviews
• Supplement:
  1
• End Date:
  20080929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/247976/cdc_247976_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]