Excretion and metabolism of 1-nitropyrene in rats after oral or intraperitoneal administration
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 was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of ( UC)NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered UC was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3-8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible. 29 references, 8 figures.
- Research Organization:
- Inhalation Toxicology Research Institute, Albuquerque, NM
- DOE Contract Number:
- AC04-76EV01013
- OSTI ID:
- 6258353
- Journal Information:
- Fundam. Appl. Toxicol.; (United States), Vol. 5
- Country of Publication:
- United States
- Language:
- English
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NITRO COMPOUNDS
EXCRETION
METABOLISM
BIOLOGICAL PATHWAYS
CARBON 14 COMPOUNDS
COMPARATIVE EVALUATIONS
EXPERIMENTAL DATA
FECES
INTRAPERITONEAL INJECTION
LIQUID COLUMN CHROMATOGRAPHY
METABOLITES
ORAL ADMINISTRATION
RATS
TRACER TECHNIQUES
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
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CLEARANCE
DATA
INFORMATION
INJECTION
INTAKE
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LABELLED COMPOUNDS
MAMMALS
MATERIALS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
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550501* - Metabolism- Tracer Techniques