Metabolism and excretion of 2-nitro-p-cresol in rats.

Abstract

Metabolism of 2-nitro- p-cresol (NPC), an important commercial chemical, was studied in female Sprague-Dawley rats, using (14)C-NPC. It was found that NPC was rapidly absorbed and excreted after an oral dose of 250 mg/kg. Approximately 90% of the administered dose was excreted into urine and less than 10% of the dose into feces for 5 days. Urinary and fecal excretion were found to the same extent after 48 h. Bile excretion amounted to approximately 25% for 2 days. Blood levels of (14)C-NPC reached the maximum concentration (39.4 micro g-equivalents/g) within 1 h, and decreased bi-exponentially. The apparent half-lives of (14)C-NPC were 3.8 h for the rapid phase and 37 h for the slow phase, respectively. From studying the distribution in organs at 1.5, 6, 24, 72 and 120 h, we found that the concentrations of radioactivity in various tissues of rats were relatively high in the stomach, intestine, liver, kidney, blood, ovary and uterus. Most organs showed the maximum concentrations at 1.5 h, except for intestine, kidney, ovary, and uterus at 6 h. There was no specific tissue retention after 72 h. Two main conjugate metabolites, glucuronide and sulfate of NPC, were detected with free NPC and 2-acetylamino- p-cresol (AAPC) in the urine. NPC was rapidly absorbed and excreted mainly into urine as the conjugate metabolites. A part of NPC was reduced to 2-amino- p-cresol, followed by acetylation to give AAPC.