Skin reservoir formation and bioavailability of dermally administered chemicals 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. Single doses of 14C-labelled phenanthrene, benzo[a]pyrene or di(2-ethylhexyl) phthalate were administered dermally to groups of four female, Hartley hairless guinea pigs which were housed individually in metabolism cages to collect urine and faeces for radioassay. The animals were sacrificed at 6 hr, 24 hr, 48 hr, 7 days or 14 days after dosing to harvest skin specimens for the determination of radioactivity by autoradiographic and liquid scintillation methods, and to determine the dose that 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 cumulative percent dose excreted in urine and faeces increased. The autoradiographic results were consistent with those obtained from the liquid scintillation method showing a gradual decrease in radioactivity grain accumulation over the time periods for the three compounds, with the highest grain density observed around hair follicles of the skin. The results of this study indicate that the chemicals left in the skin after surface washing eventually enter the systemic circulation and should be considered as part of the total dose absorbed, and that the hair follicle may play an important role in percutaneous penetration.
Chu
I
I
Health Canada, Environmental Health Directorate, Ottawa, ON.
Dick
D
D
Bronaugh
R
R
Tryphonas
L
L
D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006168:Guinea Pigs; D007271:Injections, Intradermal; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*
D001564:Benzo(a)pyrene; D004051:Diethylhexyl Phthalate