Comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disposition following pulmonary, oral, dermal, and parenteral exposures to rats.
In evaluating human health risks posed by dioxins, it is necessary to accurately predict systematic dosimetry or the fate of these chemicals. Pharmacokinetic parameters pertaining to inhalation, ingestion, and dermal absorption may be estimated using animal models. The present study was designed to assess absorption, tissue distribution, and elimination of TCDD following intratracheal instillation (itr.), oral gavage (p.o.), or intravenous administration (i.v.) of 1 nmol [3H]TCDD/kg to male rats; experimental conditions were chosen to permit comparison to a previous dermal disposition study (Banks and Birnbaum, Toxicol. Appl. Pharmacol. 107, 302-310, 1991). After treatment, rats were housed in individual metabolism cages for 3 days with daily excreta collection. Following termination, radioactivity was quantified in tissues and excreta. By 3 days postexposure, fecal excretion accounted for 22 (i.v.), 26 (itr.), and 32% (p.o.) of dose, while urinary excretion was only 2.2 (i.v.), 1.3 (itr), and 1.4% (p.o.). Pulmonary absorption was calculated as 95% of administered dose, while oral absorption was 88%. Dermal absorption of an equivalent administered dose was 40% (Banks and Birnbaum, 1991). For all exposure routes by 3 days, major tissue depots for absorbed dose were liver and fat. Distribution of absorbed dose was 37% (i.v.) and 35% (itr.) to liver and 21% (i.v.) and 16% (itr.) to fat. Oral gavage-treated rats had similar dosimetry (28-30% absorbed dose) in both liver and fat. In contrast following dermal exposure, distribution to liver and fat was 52 and 22%, respectively (Banks and Birnbaum, 1991). Results suggest that inhalation can be an important route for systemic absorption of dioxins. Moreover, all environmentally relevant routes of exposure (oral, dermal, and respiration) must be uniquely considered as important routes of systemic exposure for TCDD and related compounds.
Diliberto
J J
JJ
Pharmacokinetics Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Jackson
J A
JA
Birnbaum
L S
LS
D000273:Adipose Tissue / Q000378:metabolism; D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000072317:Polychlorinated Dibenzodioxins