Abstract
Liver function data are usually difficult to use in their original form when one wishes to compare the hepatotoxic properties of several chemical substances. However, procedures are available for the conversion of liver function data into quantal responses. These permit the elaboration of dose-response lines for the substances in question, the calculation of median effective doses and the statistical analysis of differences in liver-damaging potency. These same procedures can be utilized for estimating the relative hazard involved if one compares the liver-damaging potency to the median effective dose for some other pharmacologie parameter. Alterations in hepatic triglycerides, lipid peroxidation, and the activities of various hepatic enzymes can also be quantitiated in a dose-related manner. This permits the selection of equitoxic doses required for certain comparative studies and the selection of doses in chemical interaction studies. The quantitative problems involved in low-frequency adverse reactions and the difficulty these present in the detection of liver injury in laboratory animals are discussed.
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Selected References
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- Becker B. A., Plaa G. L. Quantitative and temporal delineation of various parameters of liver dysfunction due to alpha-naphthylisothiocyanate. Toxicol Appl Pharmacol. 1965 Sep;7(5):708–718. doi: 10.1016/0041-008x(65)90128-6. [DOI] [PubMed] [Google Scholar]
- Gehring P. J. Hepatotoxic potency of various chlorinated hydrocarbon vapours relative to their narcotic and lethal potencies in mice. Toxicol Appl Pharmacol. 1968 Nov;13(3):287–298. doi: 10.1016/0041-008x(68)90102-6. [DOI] [PubMed] [Google Scholar]
- KUTOB S. D., PLAA G. L. A procedure for estimating the hepatotoxic potential of certain industrial solvents. Toxicol Appl Pharmacol. 1962 May;4:354–361. doi: 10.1016/0041-008x(62)90046-7. [DOI] [PubMed] [Google Scholar]
- KUTOB S. D., PLAA G. L. The effect of acute ethanol intoxication on chloroform-induced liver damage. J Pharmacol Exp Ther. 1962 Feb;135:245–251. [PubMed] [Google Scholar]
- Klaassen C. D., Plaa G. L. Comparison of the biochemical alterations elicited in livers from rats treated with carbon tetrachloride, chloroform, 1,1,2-trichloroethane and 1,1,1-trichloroethane. Biochem Pharmacol. 1969 Aug;18(8):2019–2027. doi: 10.1016/0006-2952(69)90299-8. [DOI] [PubMed] [Google Scholar]
- Klaassen C. D., Plaa G. L. Relative effects of various chlorinated hydrocarbons on liver and kidney function in dogs. Toxicol Appl Pharmacol. 1967 Jan;10(1):119–131. doi: 10.1016/0041-008x(67)90134-2. [DOI] [PubMed] [Google Scholar]
- Klaassen C. D., Plaa G. L. Relative effects of various chlorinated hydrocarbons on liver and kidney function in mice. Toxicol Appl Pharmacol. 1966 Jul;9(1):139–151. doi: 10.1016/0041-008x(66)90038-x. [DOI] [PubMed] [Google Scholar]
- PLAA G. L., EVANS E. A., HINE C. H. Relative hepatotoxicity of seven halogenated hydrocarbons. J Pharmacol Exp Ther. 1958 Jul;123(3):224–229. [PubMed] [Google Scholar]
- Traiger G. J., Plaa G. L. Differences in the potentiation of carbon tetrachloride in rats by ethanol and isopropanol pretreatment. Toxicol Appl Pharmacol. 1971 Sep;20(1):105–112. doi: 10.1016/0041-008x(71)90094-9. [DOI] [PubMed] [Google Scholar]
- Traiger G. J., Plaa G. L. Relationship of alcohol metabolism to the potentiation of CCl 4 hepatotoxicity induced by aliphatic alcohols. J Pharmacol Exp Ther. 1972 Dec;183(3):481–488. [PubMed] [Google Scholar]