Disposition of 1,2,3,7,8-pentachlorodibenzofuran in the rat.
1,2,3,7,8-Pentachlorodibenzofuran (1PeCDF) is one of several toxic polychlorinated dibenzofurans (PCDFs) which are ubiquitous environmental contaminants. Related in structure and toxicity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), PCDFs have been detected in municipal and industrial effluents, PCB mixtures, and in a variety of antiseptics and preservative solutions. The objective of this study was to evaluate the distribution and elimination of 1PeCDF in the rat and to compare these parameters with that of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) and 2,3,7,8-tetrachlorodibenzofuran (TCDF). After iv administration of 0.1 mumol [3H]1PeCDF/kg, 1PeCDF was rapidly cleared from the blood and distributed to the liver, muscle, skin, and adipose tissue in a manner similar to that for other dibenzofurans. The initial pool sizes of 1PeCDF-derived radioactivity in the liver, muscle, skin, and adipose tissue were 43,35,10, and 7% of the administered dose, respectively. In all cases, loss of radioactivity from these tissues could be described by exponential decay and the initial half-lives for these tissues were 1.36, 0.03, 13, and 1 day, respectively. After redistribution from the muscle, skin, and adipose tissues to the liver, 1PeCDF was metabolized to a polar metabolite(s) and excreted from the body via the bile into the feces. No parent compound was detected in the bile and fecal excretion was the major route of elimination. Most of the radioactivity in the urine was excreted within the first day, after which less than 0.5% of the dose/day was detected. More than half of the administered dose was excreted in the urine and feces within 2 days. The whole-body half-life of related compounds is 4PeCDF much greater than 1PeCDF greater than or equal to TCDF. Therefore, persistence appears to be inversely related to the metabolism of these compounds and metabolism is inhibited by chlorine-substituted carbon atoms adjacent to the oxygen atom in the dibenzofuran ring.
Brewster
D W
DW
Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Birnbaum
L S
LS
D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics* / Q000633:toxicity; D001646:Bile / Q000378:metabolism; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D005243:Feces / Q000032:analysis; D007928:Lethal Dose 50; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D001572:Benzofurans; D004785:Environmental Pollutants; C057584:1,2,3,7,8-pentachlorodibenzofuran; C038890:2,3,4,7,8-pentachlorodibenzofuran; C014211:2,3,7,8-tetrachlorodibenzofuran