LIPID PEROXIDATION INDUCED BY SOME HALOMETHANES AS MEASURED BY INVIVO PENTANE PRODUCTION IN THE RAT

Pentane production in vivo in rats was used successfully as an index to support the concept that lipid peroxidation is involved in the toxicity of some halomethanes. The time-response relationships showed that the rats had maximum pentane production by 15-30 min following ip administration of carbon tetrachloride (CCl4), bromotrichloromethane (BrCCl3), and chloroform (CHCl3). BrCCl3 and CCl4 caused the production of the greatest amounts of pentane, CHCl3 induced a smaller amount of pentane production, and dichloromethane (CH2Cl2) did not increase pentane production over that caused by injection of the mineral oil carrier. There was a good relationship (r = 0.987; p < 0.001) between the amount of pentane produced and the bond dissociation energies of BrCCl3, CCl4, and CHCl3. This finding supports the concept that trichloromethyl radicals (·CCl3) produced by homolytic cleavage of halomethanes induce lipid peroxidation. Conjugated dienes in liver, kidney, intestine, spleen, lung, and heart were measured following administration of CCl4 and BrCCl3. There was a good correlation (r = 0.96; p < 0.01) between pentane production in vivo and conjugated diene formation in the liver. The liver accounted for 85 and 94% of the total conjugated dienes measured after administration of CCl4 and BrCCl3, respectively. The amount of pentane produced during a 30-min period following injection of 1 mmol of CCl4 corresponded to about 0.2% of the lipid peroxides, measured as conjugated dienes, in the liver following the same time period. These results suggest that liver is also the principal site of pentane production. © 1979.