Sex differences in sulfation and glucuronidation of phenol, 4-nitrophenol and N-hydroxy-2-acetylaminofluorene in the rat in vivo

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Sulfation and glucuronidation of phenol, 4-nitrophenol (4NP) and N-hydroxy-2-acetyl-aminofluorene (N-OH-AAF) were studied in adult (60 days) male and female rats. Within 3 hours almost 50% of a dose of phenol was excreted in urine as phenyl sulfate; male rats excreted slightly more phenyl sulfate than females. This probably was due to a slower excretion of phenyl sulfate by the females. No sex difference in glucuronidation of phenol was found. Over a period of 24 hours male and female rats excreted almost 35% of a dose of 4NP as 4NP-sulfate in urine and almost 40% as 4NP-glucuronide. No differences in the excretion of 4NP-conjugates were found between sexes. However, almost twice as much of a dose of N-OH-AAF was excreted after 4 hours as the N-O-glucuronide in bile and urine in female than in males. On the other hand, females excreted less of the AAF-glutathione conjugates that are derived from the reaction of AAF-N-sulfate with glutathione in vivo [Meerman et al., Chem.-Biol. Interactions, 39, 149, 1982]in bile, than males. This indicates that sulfation of N-OH-AAF is less active in females than in males. Most likely, sulfation of the phenols is catalyzed by a different sulfotransferase than that of N-OH-AAF.