Biotransformation and disposition of hexachlorocyclopentadiene in fish

Fate of hexachlorocyclopentadiene (Hex) was studied in fresh-water fish using in vivo and in vitro systems. Hex injected intraperitoneally into goldfish is readily distributed, stored and metabolized (greater than 11 organosoluble and hydrophilic metabolites). The body radioactivity in tissues declines, but levels in bile remain high, indicating biliary excretion as a major route of elimination for Hex and its metabolites. Total radioactivity eliminated in water indicated three phases with a calculated half-life (t1/2) of 7 days and predicted 90 and 95% clearance of 162 and 211 days, respectively. A 3-segment straight line model gave the best fit of the elimination data. A compartmental model indicated two elimination and one reabsorption phase. For a static system, two phases of elimination were detected with a calculated t1/2 of 9 days and predicted 90 and 95% clearance of 77 and 107 days, respectively. A compartmental model indicated that one elimination and one reabsorption phase were involved. Goldfish produced a number of organosoluble and watersoluble metabolites in vivo. Several of the organosolubles may be volatile, and at least 11 were characterized by thin-layer chromatography. The primary metabolites may react with endogenous molecules which render them more hydrophilic. Hepatic microsomal P-450 oxygenases and cytosolic GSH-transferases from bluegills may be involved in Hex metabolism. GSH can also alter HEX nonenzymically. The two hexane-extractable (in vitro) metabolites of Hex were more polar than Hex. The inhibitors of the microsomal P-450 oxygenases (piperonyl butoxide) and UDPGA-transferase (salicylamide) do not affect the toxicity of HEX to goldfish fingerlings, indicating that its toxicity may not be related to these pathways.