Excretion and Metabolism of 1-Nitropyrene in Rats after Oral or Intraperitoneal Administration

Excretion and Metabolism of 1-Nitropyrene in Rats after Oralor Intraperitoneal Administration. DUTCHER, J. S., SUN, J. D.,BECHTOLD, W. E., and UKEFER, C. J. (1985). Fundam. Appl. Toxicol.5, 287–296. Many nitro-substituted polycyclic aromatichydrocarbons (NPAHs) have been identified as environmental pollutantsand have been found to be mutagens and carcinogens in bacteriaand mammalian systems. They require metabolism to express theirbiological activity. The metabolism and excretion of 1-nitropyrene(NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal(ip) or oral administration was studied. Radiolabeled NP wasadministered to rats (10 mg NP/kg body wt), and urine and feceswere collected for 7 days. After ip administration of [¹⁴C]NP,60% of the radioactivity was found in the urine and 20% in thefeces. Likewise, 55 and 35% of the orally administered ¹⁴C wasfound in urine and feces, respectively. Both urine and feceswere analyzed by high-pressure liquid chromatography for metabolites.The majority of the radioactivity in both urine and feces wasassociated with very polar metabolites, none accounting formore than 10% of the dose. Small amounts (less than 1% of thedose) of aminopyrene (AP), acetylaminopyrene, and NP were detected.A urinary metabolite (3–8% of the dose) was found thatconverted to acetylaminopyrene phenol (two isomers) when urinewas heated overnight at 37°C at pH 4.5. More of this metabolite(2.2 times) as well as AP (1.8 times), was excreted after oralthan after ip administration of NP. The NP metabolites foundin this study demonstrate that reduction of the nitro groupis a significant route of NP metabolism in rats. Since nitroreductionappears to be necessary in the activation of NPAHs to bacterialmutagens, this indicates that similar metabolic pathways arepresent in rats (catalyzed by mammalian and/or gut bacterialenzymes) and that activation of NPAHs to carcinogens or toxinsby nitroreduction is possible.