Chronic inhalation toxicity study of 1,2-dichloroethane in rats treated with disulfiram or ethanol. Part II: disposition, metabolism and binding studies.

Details

• Personal Author:
  Alm P ; Christianson K ; Czarnecki D ; El-hawari M ; Long J ; Murrill E ; Pallas F ; Stoltz M
• Description:
  Possible mechanisms of action were sought to explain the synergistic effects of simultaneously administered 1,2-dichloroethane (107062) (EDC) and disulfiram (97778) in the production of cancer in rats. In animals receiving only EDC, blood samples revealed the presence of EDC at 15 minutes and at 2 hours following the termination of the EDC exposure. Simultaneous exposure to ethanol (64175) revealed the same concentrations of EDC in the blood. In rats simultaneously exposed to EDC and disulfiram, these EDC levels were five times higher. Expired air from rats treated with EDC contained 28 to 30 percent of the unmetabolized EDC; urine contained 47 to 55 percent of the administered dose, and fecal elimination amounted to 1 to 2 percent. In rats also treated with disulfiram, expired air contained 58 percent of the administered dose. Urinary metabolic profiles for rats treated with EDC plus disulfiram were similar to those treated with EDC alone. Binding of EDC to hepatic DNA was not changed by additional exposure to disulfiram. The authors conclude that the reduced EDC elimination as a result of the simultaneous exposure to disulfiram may have been responsible for the increased incidence of hepatic, testicular, and mammary tumors found in these rats, as opposed to changes in biotransformation and binding of the offending carcinogen. [Description provided by NIOSH]
• Subjects:
  Chlorine Compounds Energy Metabolism Inhalation Exposure Laboratories Liver Neoplasms Occupational Health Safety Solvents
• Keywords:
  Cancer-rates Chlorinated-ethanes Contract-200-82-2508 Inhalants Laboratory-animals Liver-disorders Metabolic-study NIOSH-Contract
• Document Type:
  Text
• Funding:
  Contract
• Genre:
  Final Contract Report
• Place as Subject:
  Missouri ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-52
• NIOSHTIC Number:
  nn:00165812
• NTIS Accession Number:
  PB87-165064
• Citation:
  Midwest Research Institute, Kansas City, Missouri 1986 Jul; :1-52
• CAS Registry Number:
  1,2-Dichloroethane (CAS RN 107-06-2) ; Ethanol (CAS RN 64-17-5) ; Tetraethylthiuram disulfide (CAS RN 97-77-8)
• Federal Fiscal Year:
  1986
• Performing Organization:
  Midwest Research Institute, Kansas City, Missouri
• Peer Reviewed:
  False
• Source Full Name:
  Midwest Research Institute, Kansas City, Missouri
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4bcd5a57a93466b4926d177f97b7c723a7604aecb0b68c7cf74083d2610f5af348903a44cdc372aa146dc94600574839f686be49462d9269a85c2dd6273ee296
• Download URL:
  https://stacks.cdc.gov/view/cdc/185077/cdc_185077_DS1.pdf
• File Type:
  [PDF - 2.27 MB ]