Excretion, Distribution and Metabolic Fate of Sodium o-Phenylphenate and o-Phenylphenol in the Rat

Abstract

Excretion, organ distribution and metabolic fate of sodium o-phenylphenate (OPP-Na) and o-phenylphenol (OPP) were studied in male rats mainly with 14C-compounds. Both OPP-Na and OPP were rapidly excreted in the urine and feces following oral administration. About 85-90% of the dose appeared in the urine, but only 3-4% in the feces within 48 hr. Biliary excretion amounted to about 27% of the dose 72 hr after oral administration of OPP-Na, and was higher than that in the feces. This fact suggests that enterohepatic circulation of OPP metabolites occurs in the body. No significant retention was observed in organs and tissues on Days 1, 3 and 7 for OPP-Na, and Days 1 and 7 for OPP after dosing. Autoradiographic studies of intact rats gave the same results. The major metabolites in the urine were the conjugates of OPP after a single oral administration of OPP-Na. OPP, 2, 5-dihydroxydiphenyl (DHD) and 2phenyl-p-benzoquinone (PBQ) in a free state were identified in the pooled urine of the rats receiving the 2% OPP-Na diets for 2 weeks. No remarkable difference was observed in excretion pattern or metabolites between OPP-Na and OPP in the single dose experiments.

Effects of pH on Nonenzymatic Oxidation of Phenylhydroquinone: Potential Role in Urinary Bladder Carcinogenesis Induced by o-Phenylphenol in Fischer 344 Rats

“…The primary routes of OPP metabolism are shown in Scheme 1. o-Phenylphenol is metabolized enzymatically into unconjugated phenylhydroquinone (PHQ), phenylbenzoquinone (PBQ), and glucuronide and sulfate conjugates, with the urinary levels of glucuronide conjugates as well as free metabolites increasing with dose (10)(11)(12)(13)(14).…”

“…The primary routes of OPP metabolism are shown in Scheme . o -Phenylphenol is metabolized enzymatically into unconjugated phenylhydroquinone (PHQ), phenylbenzoquinone (PBQ), and glucuronide and sulfate conjugates, with the urinary levels of glucuronide conjugates as well as free metabolites increasing with dose ( − ). Due to the reactivity of quinoid compounds, it has been proposed that PBQ is responsible for the toxic effects observed in rats administered high doses of OPP and SOPP ( , ).…”

o‐Phenylphenol und o‐Phenylphenol‐Natrium [MAK Value Documentation in German language, 1988]

“…Nach akuter oraler Verabreichung hoher Dosen (von bis zu 500 mg/kg KG) an OPP und OPP-Na werden praktisch 100% der verabreichten Stoffe überwiegend in Form von Schwefelsäure-oder Glucuronsäurekonjugaten in Urin (etwa 95%) und Faeces (etwa 5 %) wiedergefunden, wobei etwa 80% (OPP-Na) bzw. etwa 60 % (OPP) bereits innerhalb der ersten 12…”

“…Der Metabolismus von OPP und OPP-Na wurde überwiegend an der Ratte untersucht [7][8][9][10][11][12][13][14][15][16] und ist weitgehend aufgeklärt. Weitere Untersuchungen zum Metabolismus von OPP wurden an Hund und Katze [17][18][19][20], an der Maus [21] sowie an isolierten Hepatozyten der Ratte [22] durchgeführt.…”

DNA damage induced by metabolites of o-phenylphenol in the presence of copper(II) ion

“…It is widely accepted that many carcinogens are readily converted to reactive intermediates by drug-metabolizing enzymes. The metabolites of OPP in the free form include Di-OH-BP and PBQ (8,11,12). Morimoto et al reported that DNA damage was induced in urinary bladder epithelium of male rats treated with PBQ (13).…”