Dose-Response Relationships in Ketone-Induced Potentiation of Chloroform Hepato- and Nephrotoxicity

Details

• Personal Author:
  Brown EM ; Hewitt WR
• Description:
  Chloroform (CHCl3)-induced hepato- and nephrotoxicity was evaluated in male, Fischer 344 rats pretreated with various dosages (1.0 to 15.0 mmol/kg, po) of acetone (Ac), 2-butanone (Bu), 2-pentanone (Pn), 2-hexanone (Hx), or 2-heptanone (Hp). The CHCl3 challenge dosage (0.5 ml/kg, ip) produced slight centrilobular hydropic degeneration and patchy degeneration and necrosis in the proximal tubules of corn oil-pretreated rats. Each of the ketones studied produced a dose-related potentiation of CHCl3 liver and kidney injury. CHCl3 produced extensive tubular and centrilobular necrosis when administered to ketone-pretreated rats. The relationship between ketone dosage and the magnitude of the potentiated response was nonlinear. Maximum potentiation of CHCl3 toxicity occurred in the dosage range of 5.0 to 10.0 mmol ketone/kg. Ketone dosages greater than 10.0 mmol/kg were associated with a reduction in the degree of CHCl3 injury. At the lowest ketone dosage (1.0 mmol/kg), potentiating capacity appeared to be related to ketone carbon skeleton length. No differences in potentiating capacity were discernable between the ketones at dosages of 5.0 to 10.0 mmol/kg. Thus, whether or not there is a relationship with carbon chain length and potentiation depends upon the dosage of the ketone. [Description provided by NIOSH]
• Subjects:
  Animals Occupational Health Safety Toxicology
• Keywords:
  Animal Studies Chloroform Dose Response Kidney Toxins Liver Tissue Renal Toxicity Toxic Effects
• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• 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:
  437-453
• Volume:
  76
• Issue:
  3
• NIOSHTIC Number:
  nn:20060576
• Citation:
  Toxicol Appl Pharmacol 1984 Dec; 76(3):437-453
• CAS Registry Number:
  Chloroform (CAS RN 67-66-3)
• Federal Fiscal Year:
  1985
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4ff503bbb7616d28f1365616877b061f57a81d92914bf77c0fe7e5d729bdf54a00960ae420b44656e4e92fd76f4ad81c34cc9d68c97e34237e3457b0e5b348bf
• Download URL:
  https://stacks.cdc.gov/view/cdc/224439/cdc_224439_DS1.pdf
• File Type:
  [PDF - 1.55 MB ]