Comparative dermal absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin and three polychlorinated dibenzofurans.
Polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) are toxic environmental contaminants which have the potential to accumulate in human tissues. In order to examine the potential for systemic exposure following dermal exposure, the absorption, distribution, and elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1PeCDF), and 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) were evaluated in male F344 rats. TCDD (0.00015, 0.001, 0.01, 0.1, 0.5, and 1.0 mumol/kg) and the three PCDFs (0.1, 0.5, and 1.0 mumol/kg) were applied to a preclipped region on the back of the rat and covered with a perforated cap. The rats were held in individual metabolism cages for 3 days. In animals administered 0.1 mumol/kg, the absorption of TCDF was greater than that of 4PeCDF, 1PeCDF, and TCDD. Relative absorption (percentage of administered dose) declined with increasing dose while the absolute absorption (microgram/kg) increased nonlinearly with dose. Absorption of TCDF at 0.1 mumol/kg was 48% of the administered dose which was significantly greater than that of the other compounds. At this dose, absorption of 4PeCDF was greater than that of TCDD. Absorption at the higher doses was similar for all four compounds. Maximum relative absorption of TCDD (approximately 40% of the administered dose) was obtained at 0.001 and 0.00015 mumol/kg. Major tissue depots for these four chemicals included liver, adipose, skin, and muscle tissue; however, the liver:fat ratio for 4PeCDF was approximately fourfold higher than that for the other three compounds. When normalized to 100% of dose absorbed, the distribution of 4PeCDF-derived radioactivity in liver and adipose tissue was similar to that previously observed after oral and iv administration. In animals administered 0.1 mumol TCDF or 1PeCDF/kg, 56 and 32% of the respective absorbed dose was excreted as polar metabolites within 3 days. Very little of the absorbed dose of either TCDD (approximately 10%) or 4PeCDF (approximately 2%) was eliminated. Results indicate that the dermal absorption of these compounds is incomplete and that systemic toxicity following acute dermal exposure to levels found in the environment is unlikely.
Brewster
D W
DW
Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Triangle Park, North Carolina 27709.
Banks
Y B
YB
Clark
A M
AM
Birnbaum
L S
LS
D000279:Administration, Cutaneous; D000818:Animals; D001572:Benzofurans / Q000032:analysis / Q000493:pharmacokinetics*; D004147:Dioxins / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000032:analysis*; D005243:Feces / Q000032:analysis; D007220:Industrial Waste / Q000032:analysis; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000032:analysis / Q000493:pharmacokinetics*; D011108:Polymers; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption; D014018:Tissue Distribution
D001572:Benzofurans; D004147:Dioxins; D004785:Environmental Pollutants; D007220:Industrial Waste; D000072317:Polychlorinated Dibenzodioxins; D011108:Polymers; C016068:polychlorodibenzofuran; C057584:1,2,3,7,8-pentachlorodibenzofuran; C038890:2,3,4,7,8-pentachlorodibenzofuran; C014211:2,3,7,8-tetrachlorodibenzofuran