Use of pentachlorophenol as long-term inhibitor of sulfation of phenols and hydroxamic acids in the rat in vivo.

Inhibition of sulfation of the phenolic compound harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole) by pentachlorophenol (PCP) was studied in the Wistar rat: PCP was administered in various ways to find a convenient method for long-term inhibition of sulfation. High doses of PCP or sodium pentachlorophenolate (NaPCP) in the diet (350 ppm) or NaPCP in the drinking water (1.4 mM) of Wistar rats for one week inhibited the sulfation of harmol by 30-45%. The plasma concentration of PCP in rats with NaPCP (1.4 mM) in their drinking water was highest (270 microM) in the period that the animals were kept in the dark and consumed food and water. This is explained by a rapid elimination: the elimination of PCP from plasma, after intravenous administration, showed a biphasic disappearance curve with half-lives of 2.17 and 7.24 hrs, respectively. This is much faster than in Sprague-Dawley rats. A log-linear correlation was found between the plasma concentration of pentachlorophenol and the inhibition of harmol sulfation. Although administration of NaPCP to rats in their drinking water inhibited the sulfation of harmol only by 45%, it inhibited the sulfation of the carcinogenic arylhydroxamic acid N-hydroxy-2-acetylaminofluorene by 70-75%.