The effect of chlorine substitution on the dermal absorption of polychlorinated biphenyls.
The fate of selected mono-, di-, tetra-, and hexachlorobiphenyls was investigated following single dermal administration (0.4 mg/kg) to determine the effects of chlorine substitution on the dermal absorption and disposition of polychlorinated biphenyls (PCBs). Single dermal doses of 14C-labeled mono-, di-, tetra-, and hexachlorobiphenyls were administered to 1-cm2 areas on the backs of F-344 male rats. Unabsorbed radioactivity was removed from the dose site either at euthanasia or 48 h postdose. Distribution of radioactivity in the dose site and selected tissues was determined by serial sacrifice at time points up to 2 weeks. Dermal penetration varied inversely with degree of chlorination and at 48 h ranged from ca. 100% for monochlorobiphenyl to ca. 30% for the hexachlorobiphenyl. Penetration rate constants correlated well with log kow. PCBs were retained in the epidermis for up to 2 weeks postdose. The data from these studies suggest that systemic absorption of PCBs involves a combination of sequential processes including penetration across the stratum corneum, possibly metabolism in the epidermis and/or dermis, adsorption to proteins, and finally absorption into the systemic circulation. The skin favors the rapid absorption of less chlorinated PCBs, but the relatively rapid metabolism and elimination of these compounds would result in lower body burdens. More highly chlorinated PCBs penetrate less rapidly but remain in the site of exposure and slowly enter the systemic circulation. The dermal absorption of a commercial PCB mixture was modeled, and the results suggest that the net result of the differences in absorbance rates would be a greater body burden of higher chlorinated PCBs relative to those that have a lower chlorine content.
Garner
C E
CE
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Matthews
H B
HB
D000279:Administration, Cutaneous; D000818:Animals; D001822:Body Burden; D002250:Carbon Radioisotopes; D002713:Chlorine / Q000737:chemistry; D004781:Environmental Exposure; D004817:Epidermis / Q000378:metabolism; D008297:Male; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D002713:Chlorine; D011078:Polychlorinated Biphenyls