Age-related changes in dermal absorption of 2,3,7, 8-tetrachlorodibenzo-p-dioxin and 2,3,4,7,8-pentachlorodibenzofuran.
Changes in the structure and function of aged skin may alter percutaneous absorption of environmental compounds such as the halogenated aromatic hydrocarbons. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and 2,3,4,7,8-penta-chlorodibenzofuran (4PeCDF) were previously found to be poorly absorbed in 3 months male Fischer 344 rats within 3 days after dermal administration. In order to examine age-related changes in dermal absorption and changes in potential for systemic exposure, the absorption, distribution, and elimination of TCDD and 4PeCDF were examined in male Fischer 344 rats of various ages (TCDD: 10, 36, and 96 week; 4PeCDF: 10, 36, 64, 96, and 120 week). Each compound was applied at a dose of 0.1 mumol/kg and/or 0.04 mumol in 60 microliters acetone to a preclipped region of the back and covered with a stainless-steel perforated cap. Rats were housed in individual metabolism cages for 3 days. Dermal absorption of both compounds was decreased in older age groups compared to 10 week rats. The major tissue depots for both compounds were liver, adipose, skin, and muscle and in comparable age groups, the liver:fat ratio was greater in 4PeCDF-treated animals. Age-related changes in the distribution of the administered dose and the absorbed dose varied with the compound as well as the depot. Elimination of TCDD and 4PeCDF was limited at all ages. Results indicate that percutaneous absorption of these compounds is decreased in older animals, suggesting that systemic bioavailability may be decreased in older organisms following dermal exposure to TCDD or 4PeCDF.
Banks
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YB
Experimental Toxicology Branch, National Institute of Environmental Health Sciences, Reseach Triangle Park, North Carolina 27709.
Brewster
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Birnbaum
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LS
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics* / Q000652:urine; D001823:Body Composition / Q000187:drug effects; D004147:Dioxins / Q000493:pharmacokinetics*; D005243:Feces / Q000032:analysis; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption / Q000502:physiology*; D014018:Tissue Distribution
D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; C038890:2,3,4,7,8-pentachlorodibenzofuran