The effect of chlorine substitution on the disposition of polychlorinated biphenyls following dermal administration.
The fate of selected polychlorobiphenyls (PCBs) was investigated following single dermal administration (0.4 mg/kg) to determine the effects of chlorine content and position on the disposition of PCBs following dermal absorption. Single dermal doses of (14)C-labeled mono-, di-, tetra- and hexachlorobiphenyls were administered to 1 cm(2) areas on the backs of F-344 male rats. Distribution of radioactivity in selected tissues and excreta was determined by serial sacrifice at time points up to 2 weeks. Unabsorbed radioactivity was removed from the dose site at either sacrifice or 48 h post-dose. The time course of radioactivity in the tissues showed a dependence on rate and extent of absorption. The most rapidly absorbed PCBs reached peak tissue concentrations at early times and were cleared from the tissues rapidly. The higher chlorinated PCBs were slowly absorbed and tended to accumulate in the adipose and skin after removal of unabsorbed dose. Excretion of absorbed radioactivity varied with chlorine content ranging from 27% to ca. 100% at 2 weeks post-dose. Excretion profiles following dermal doses tended to differ from profiles following equivalent IV doses, as did the metabolite profiles in excreta. Skin slice incubation experiments suggested that first pass metabolism in the dermal dose site was responsible for metabolism and disposition differences between routes of administration. The data further suggest that the rate of absorption, and therefore the disposition of PCBs following dermal administration may be mediated, either in part or fully, by transdermal metabolism.
Garner
C Edwin
CE
Department of Drug Metabolism and Disposition, RTI International, Research Triangle Park, NC 27709, USA. cegarner@rti.org
Demeter
Jennifer
J
Matthews
H B
HB
D000273:Adipose Tissue / Q000378:metabolism; D000279:Administration, Cutaneous; D000818:Animals; D019540:Area Under Curve; D002250:Carbon Radioisotopes; D002713:Chlorine / Q000737:chemistry*; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009132:Muscles / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; C035976:2,4,2',4'-tetrachlorobiphenyl; D002713:Chlorine; D011078:Polychlorinated Biphenyls; C029861:4,4'-dichlorobiphenyl; C027310:2,4,6,2',4',6'-hexachlorobiphenyl