Cytochrome P450-Dependent Metabolism of Trichloroethylene: Interindividual Differences in Humans

Details

• Personal Author:
  Garrett CM ; Lipscomb JC ; Snawder, John E.
• Description:
  Interindividual differences in cytochrome-P450 dependent metabolism of trichloroethylene (79016) (TRI), an industrial solvent and common groundwater contaminant, were assessed in humans. The degree to which the step whereby TRI is metabolized through chloral-hydrate (302170) to compounds such as trichloroacetic-acid (76039) and dichloroacetic-acid (79436) varies between individuals was evaluated in a sample set of 23 human hepatic microsomal fractions. Significant variability in TRI metabolism between samples was observed. TRI metabolism was dependent on cytochrome-P450 2E1 (CYP2E1). Microsomal chloral-hydrate formation was correlated with the activity toward routine CYP2E1 substrates and with immunologically detectable CYP2E1 protein. CYP2E1 appeared to be the predominant form of cytochrome-P450 responsible for TRI metabolism in humans; it catalyzed more than 60% of total microsomal TRI metabolism. The involvement of other CYP forms was also assessed; CYP1A and CYP3A formed chloral-hydrate at much lower rates than CYP2E1. The authors conclude that humans are not uniform in their capacity for cytochrome-P450 dependent metabolism of TRI; increased CYP2E1 activity may increase susceptibility to TRI induced toxicity. [Description provided by NIOSH]
• Subjects:
  Chlorine Compounds Enzymes Liver Manufacturing And Industrial Facilities Occupational Health Oxidants Risk Assessment Safety Solvents Toxicology
• Keywords:
  Chlorinated-ethylenes Enzyme-activity Hepatotoxicity Industrial-hazards Liver-microsomal-metabolism Oxidative-metabolism Risk-analysis
• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DBBS - Division of Biomedical and Behavioral Sciences
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  311-318
• Volume:
  142
• Issue:
  2
• NIOSHTIC Number:
  nn:00238403
• Citation:
  Toxicol Appl Pharmacol 1997 Feb; 142(2):311-318
• CAS Registry Number:
  Chloral hydrate (CAS RN 302-17-0) ; Dichloroacetic acid (CAS RN 79-43-6) ; Trichloroacetic acid (CAS RN 76-03-9) ; Trichloroethylene (CAS RN 79-01-6)
• Federal Fiscal Year:
  1997
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e8ac61ddbc4be2551e697b5be6e59085756ca81fe7965d7505b071d8d80704794edd5ccfca6d5586c9a7a84e79c656f7e14f0f71daf1c4afda0fc0582abd75da
• Download URL:
  https://stacks.cdc.gov/view/cdc/197920/cdc_197920_DS1.pdf
• File Type:
  [PDF - 104.08 KB ]