Maturational changes in dermal absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Fischer 344 rats.
An earlier study indicated that percutaneous absorption of a 40-nmol dose of TCDD decreased with aging in rats, suggesting that the potential for systemic exposure following dermal contact would be decreased in older age groups. In this study, maturational changes in potential for systemic exposure to TCDD following dermal application of a low dose (200 pmol) of this chemical were examined in male Fischer 344 rats. Absorption, tissue distribution, and elimination of TCDD, measured as TCDD-derived radioactivity, were examined 72 hr after dermal application of 200 pmol [3H]TCDD (111 pmol/cm2 applied over 1.8 cm2) to the interscapular region of 3-, 5-, 8-, 10-, and 36-week-old rats. The dose was applied in 60 microliters acetone and the application site was covered with a perforated metal cap; animals were held in individual metabolism cages. Dermal absorption was greatest in 3-week-old rats (approximately 129 pmol; approximately 64% of the administered dose), decreasing to approximately 80 pmol (approximately 40%) in 5-, 8-, and 10-week-old rats and to 45 pmol (approximately 22%) in 36-week-old rats. In each age group, 70 to 80% of the radioactivity remaining at the application site 72 hr after dosing could be removed with acetone swabs. Major tissue depots of radioactivity were liver and fat; skin and muscle were minor depots. Changes in distribution of absorbed TCDD-derived radioactivity reflected changes in body mass of these depots; however, tissue concentration also varied. Whole body dissection was performed on rats to determine body mass of tissue depots. Adipose tissue content (Y) increased linearly with body weight (X), Y = 0.03X + 2.1 (r2 = 0.95). Elimination of absorbed TCDD-derived radioactivity was incomplete in all age groups with larger residues being recovered in the carcass. Results indicate that TCDD is absorbed to a greater degree through skin of very young animals and that a significant decrease in potential for systemic exposure may occur during maturation and again during aging.
Anderson
Y B
YB
Experimental Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Jackson
J A
JA
Birnbaum
L S
LS
D000279:Administration, Cutaneous; D000375:Aging / Q000502:physiology; D000818:Animals; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption / Q000502:physiology*; D014018:Tissue Distribution
D000072317:Polychlorinated Dibenzodioxins