Nephrotoxic Interactions between Ketonic Solvents and Halogenated Aliphatic Chemicals

Nephrotoxic Interactions between Ketonic Solvents and HalogenatedAliphatic Chemicals. Hewitt, W. R., and Brown, E. M. (1984).Fundam. Appl. Toxicol. 4, 902–908. Recent studies haveindicated that (1) ketonic solvents and ketogenic chemicalscan potentiate the nephrotoxic and hepatotoxic effects of oneor more halogenated hydrocarbons; and (2) the relative abilityof ketones to potentiate the liver injury produced by chloroform(CHCl₃) may be influenced by the carbon skeleton length of theketone. Although five ketones (acetone, 2-butanone, 2-pentanone,2-hexanone, (HX), and 2-heptanone) increased CHCl₃-induced kidneyand liver injury in male, Fischer 344 rats, no relationshipbetween ketone chain length and potentiating capacity was observed.HX potentiated the CHCl₃-induced depletion of hepatic glutathionecontent and increased the irreversible binding of ^l4CHCl₃-derivedradiolabel to hepatic constituents. In contrast, CHCl₃ did notalter glutathione content in the renal cortex of either vehicle-or HX-pretreated rats. Although HX increased the binding of¹⁴C from ¹⁴CHCl₃ to renal cortical macromolecules, the magnitudeof the increase was unremarkable, approaching only the extentof hepatic ¹⁴C binding in vehicle-pretreated rats challengedwith ^l4CHCl₃. Since the severity of renal and hepatic injurywas comparable in rats receiving the combination of HX + CHCl₃,it appeared that HX potentiated CHCl₃ nephro- and hepatotoxicityby different mechanisms. Ketone pretreatment did not potentiatethe renal injury produced by potassium dichromate or hexachloro-l,3-butadiene.