Glutathione conjugate formation from hexachlorocyclohexane and pentachlorocyclohexene by rat liver in vitro

1. Metabolites of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were extracted from the bile of TCDD-treated dogs and administered by gavage to bile-duct-cannulated rats and also to an intact rat.

2. Radioactivity of the TCDD metabolites was rapidly cleared from the body of the rats, indicating that bioaccumulation of these compounds does not occur.

3. Biliary excretion was the most important route of elimination in the cannulated rats and amounted to > 30% of the administered dose within 24h. TCDD metabolites were also eliminated to a minor extent by the kidneys. The combined recovery of radioactivity in faeces, bile and urine after 24h accounted for >85% of the dose.

4. The intact animal exhibited a somewhat different kinetic behaviour in that only 13% dose was excreted in faeces and urine after 24h, which indicates enterohepatic circulation. The administered radioactivity was completely recovered after 72?h.

5. Results from the present experiments indicate that metabolism of TCDD is the ratelimiting step in elimination of TCDD from the liver. Interspecies variability in the toxicity of TCDD may in part be attributable to different rates at which the species metabolize and excrete TCDD.