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

ScholarsArchive at Oregon State University

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Title Hexachlorophene : its absorption, distribution, excretion, and biotransformation in the rat and rabbit and in vitro interaction with rat liver microsomes
Names Gandolfi, Allen Jay (creator)
Buhler, D. R. (advisor)
Date Issued 1972-10-26 (iso8601)
Note Graduation date: 1973
Abstract 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.
Genre Thesis/Dissertation
Topic Hexachlorophene
Identifier http://hdl.handle.net/1957/45305

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