SKIN RESERVOIR FORMATION AND BIOAVAILABILITY OF DERMALLY ADMINISTEREDCHEMICALS IN HAIRLESS GUINEA-PIGS

There is concern as to whether dermally applied chemicals that remain in the skin after exposure are bioavailable and should be included as part of the systemic dose; this study was conducted to investigate the temporal relationship between the skin depot and absorbed dose. Singl e doses of C-14-labelled phenanthrene, benzo[a]pyrene or di(2-ethylhex yl) phthalate were administered dermally to groups of four female, Har tley hairless guinea pigs which were housed individually in metabolism cages to collect urine and faeces for radioassay. The animals were sa crificed at 6 hr, 24 hr, 48 hr, 7 days or 14 days after dosing to harv est skin specimens for the determination of radioactivity by autoradio graphic and liquid scintillation methods, and to determine the dose th at remained in the body. It was found that for all three compounds the amount of chemical left in the skin decreased over time while the cum ulative percent dose excreted in urine and faeces increased. The autor adiographic results were consistent with those obtained from the liqui d scintillation method showing a gradual decrease in radioactivity gra in accumulation over the time periods for the three compounds, with th e highest grain density observed around hair follicles of the skin. Th e results of this study indicate that the chemicals left in the skin a fter surface washing eventually enter the systemic circulation and sho uld be considered as part of the total dose absorbed, and that the hai r follicle may play an important role in percutaneous penetration.