Studies in detoxication. 76. The metabolism of halogenobenzenes. 1:2:3:4-, 1:2:3:5- and 1:2:4:5-tetrachlorobenzenes

Abstract

The metabolic fate of 1,2,3,4-, 1,2,3,5- and 1,2,4,5-tetrachlorobenzenes in rabbits has been investigated. 1,2,3,4-Tetrachlorobenzene (does 0.5 g/kg orally) is slowly metabolized and about 43% is oxidized in 6 days to 2,3,4,5-tetra-chlorophenol, which is excreted in the urine, partly unchanged and partly conjugated. About 5% is eliminated in the feces, 8% in the expired air and some 10% is still in the tissues after 6 days. There is some evidence that a small proportion (2%) of the dose is partly dechlorinated, probably in the gut. 1,2,3,5-Tetrachlorobenzene is very slowly metabolized. Only about 5% is oxidized to and excreted as 2,3,4,6-tetrachlorophenol in 6 days. Some 14% is eliminated unchanged in the feces, 12% in the breath and 23% remains in the tissues after 6 days. There is evidence that some 9%3 of the dose is dechlorinated and eliminated in the expired air as less chlorinated benzenes. Some 5% of the dose may also be excreted in the urine as di- and trichlorophenols. Injected 1,2,3,5-tetrachlorobenzene is partly excreted as such in the feces, probably via the bile. 1,2,4,5-Tetrachlorobenzene appears to be the least readily metabolized of the 3 isomers. Only about 2% is converted into 2,3,5,6-tetrachlorophenol in 6 days; 48% of the dose was found in the tissues after 6 days, and 16% was in the feces and 2% in the expired air. Dechlorination products could account for 15% of the dose, about 10% of the dose appearing in the expired air as less chlorinated benzenes and 5% in the urine as di- and trichlorophenols. Dechlorination of the tetrachlorobenzenes is believed to occur in the gut, probably under the influence of bacteria.