IN-VIVO DISPOSITION OF P-SUBSTITUTED PHENOLS IN THE YOUNG-RAT AFTER INTRAPERITONEAL AND DERMAL ADMINISTRATION

The objective of this study was to examine the 120-hr disposition of p henol and four p-substituted congeners after ip and dermal administrat ion in the 29-day-old female rat. The dermal absorption was very high (66-80% of the dose) for phenol, cyanophenol, heptyloxyphenol and nitr ophenol, but minimal for hydroxybenzoic acid (2%). The major portion o f the dose for all of the phenols not absorbed dermally in 24h was was hed from the skin. Only minor amounts (1-2%) were detected in the trea ted skin at 120 hr. Urinary excretion was the predominant means of eli mination for these phenols and occurred primarily within 24 hr after d ermal and ip administration. However, the excretion of heptyloxyphenol after administration by both routes differed from that of the other c ompounds, with more of it detected in the faeces. The profile of metab olites in urine (collected at 12-24 hr) from the animals dermally trea ted with phenol, cyanophenol, heptyloxyphenol and nitrophenol showed o nly peaks that eluted earlier than the parent compound, which suggests that conjugates or more polar metabolites were formed and excreted. T he difference in dermal absorption between hydroxybenzoic acid and the other phenols may be due to potential ionization of the p-substituted carboxylic acid group of hydroxybenzoic acid. This suggests that, at least for the phenols examined in this study, physicochemical characte ristics other than just lipophilicity can affect in vivo dermal absorp tion. (C) 1997 Elsevier Science Ltd.