Graduate Thesis Or Dissertation
 

Hexachlorophene : its absorption, distribution, excretion, and biotransformation in the rat and rabbit and in vitro interaction with rat liver microsomes

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  • The fate of hexachlorophene, a widely used bactericide, was investigated using both intact male rats and rabbits and liver microsomes from male rats. Hexachlorophene administered intraperitoneally was found to be rapidly absorbed and distributed to all the tissues of the animals. Excretion of the chemical in both species occurred slowly, with 48-83% of the dose appearing in the feces as unchanged hexachlorophene plus a small amount of hexachlorophene glucuronide. The rabbit and rat excreted 21-25% and 4-8% of the dose, respectively, in the urine. A glucuronide conjugate of hexachlorophene accounted for over one-half of the urinary metabolites with the remainder being unchanged hexachlorophene. In less than four days, about 30-45% of hexachlorophene dose was excreted in the bile as a glucuronide conjugate. Extra-biliary excretion of hexachlorophene or its metabolites was also suggested. Hexachlorophene was shown to undergo enterohepatic circulation in the rat, which would explain its long half-life in animals and its excretion primarily via the feces. The glucuronide conjugate of the bisphenol excreted in the rat bile and in the rabbit urine was identified as hexachlorophene monoglucuronide. Hexachlorophene was shown not to be metabolized or conjugated in vitro by the rat liver microsomal enzyme systems. Microsomes were shown to strongly bind large amounts of hexachlorophene. Furthermore, at low concentrations, hexachlorophene inhibited microsomal 0-demethylase, nitroreductase, and glucuronide synthetase activities. Hexachlorophene also caused a decrease in microsomal cytochromes P-450 and b5 absorbancies, suggesting that interference with these microsomal components may be responsible for the observed in vitro inhibition of microsomal enzyme activity.
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