Metabolism and disposition of 4-t-butylcatechol in rats and mice

4-t-Butylcatechol (TBC) is an antioxidant used primarily as a polymerization inhibitor for reactive monomers. Annual production and use of TBC in the United States is approximately 1.5 million pounds. The absorption, tissue distribution, metabolism, and excretion of [(14)C]TBC, labeled in the methine carbon, was investigated in male Fischer 344 rats and B6C3F(1) mice after i.v., oral, and dermal administration. Oral (2 and 200 mg/kg in rats; 3 and 300 mg/kg in mice) and dermal (0.6, 6, and 63 mg/kg in rats; 1.3 and 157 mg/kg in mice) doses of TBC were well absorbed, then rapidly metabolized and excreted primarily in urine. Dermal absorption of the highest dose in the rat (87% of the 63 mg/kg dose) was significantly higher than that of the two lower doses (0.6 and 6 mg/kg, 44 and 57%, respectively). Dermally administered TBC was also well absorbed in the mouse (72-86%). Polar metabolites of TBC comprise all of the radioactivity in the urine of both species after all routes of administration. These were shown to consist mostly of the sulfate conjugates (and lesser amounts of the glucuronides) of TBC and of a less polar metabolite. The deconjugated metabolite was isolated and determined by mass spectrometry and (1)H-NMR to be mono-O-methylated TBC.