Effects of the exposure profile on the inhalation toxicity of carbon tetrachloride in male rats

Authors

  • M. Bogers,

    1. Department of Veterinary Pharmacology, Pharmacy and Toxicology, University of Utrecht, Utrecht, The Netherlands
    Search for more papers by this author
  • L. M. Appelman,

    1. TNO-CIVO Toxicology and Nutrition Institute, PO Box 360, 3700 AJ Zeist, The Netherlands
    Current affiliation:
    1. Directorate-General of Labour, PO Box 69, 2270 MA Voorburg, The Netherlands
    Search for more papers by this author
  • V. J. Feron,

    Corresponding author
    1. TNO-CIVO Toxicology and Nutrition Institute, PO Box 360, 3700 AJ Zeist, The Netherlands
    • TNO-CIVO Toxicology and Nutrition Institute, PO Box 360, 3700 AJ Zeist, The Netherlands
    Search for more papers by this author
  • R. B. Beems,

    1. TNO-CIVO Toxicology and Nutrition Institute, PO Box 360, 3700 AJ Zeist, The Netherlands
    Search for more papers by this author
  • W. R. F. Notten

    1. Directorate-General of Labour, Ministry of Social Affairs and Employment, Voorburg, The Netherlands
    Current affiliation:
    1. TNO Medical Biological Laboratory, PO Box 45, 2280 AA Rijswijk, The Netherlands
    Search for more papers by this author

Abstract

To examine the effect of the exposure pattern on the inhalation toxicity of carbon tetrachloride (CCI4) two 4-week inhalation studies with this compound were carried out in male rats at basic exposure concentrations of 63 and 80 ppm and basic exposure periods of 6 hours per day, 5 days per week. The two main variables studied were interruption of the daily 6-hour exposures by 1.5 hours (2 × 3-hour exposures with a non-exposure interval of 1.5 hour), and peak loads of 5–7 times the basic concentration with or without 1.5-hour interruption of the daily 6-hour exposures. Adverse effects of CCI4 included abnormal activities of several enzymes in serum and liver, decreased quantity of microsomal proteins in the liver, increased relative liver weight, and hydropic and fatty degeneration of hepatocytes. As compared with uninterrupted, interrupted exposures increased more the activities of glutamic oxalacetic and glutamic pyruvic transaminase in serum; peak exposures only slightly affected these enzyme activities. Uninterrupted exposures caused less severe fat accumulation in and hydropic degeneration of liver cells than interrupted exposures with or without peak loads. In addition, uninterrupted exposure to 63 ppm CCI4 with peak loads resulted in more severe hydropic liver degeneration than uninterrupted exposure to the same concentration without peak loads. It was concluded that interruption of the daily 6-hour exposures by 1.5 hour did not result in less severe but rather in slightly more severe hepatotoxicity, and peak loads superimposed on a fixed concentration only slightly aggravated the toxic effects of CCI4 on the liver.

Ancillary