Maturational changes in dermal absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Fischer 344 rats. 1993

Y B Anderson, and J A Jackson, and L S Birnbaum
Experimental Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.

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.

UI MeSH Term Description Entries
D008297 Male Males
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D000072317 Polychlorinated Dibenzodioxins Dibenzodioxin derivatives that contain multiple chloride atoms bound to the benzene ring structures. TCDD,Tetrachlorodibenzodioxin,2,3,7,8-Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo-p-dioxins,Dibenzo(b,e)(1,4)dioxin, 2,3,7,8-tetrachloro-,PCDD,Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzodioxin,Polychlorodibenzo-4-dioxin,Polychlorodibenzo-p-dioxin,Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo p dioxins,Dibenzo-p-dioxins, Chlorinated,Dibenzo-p-dioxins, Polychlorinated,Dibenzodioxin, Polychlorinated,Dibenzodioxins, Polychlorinated,Polychlorinated Dibenzo p dioxins,Polychlorodibenzo 4 dioxin,Polychlorodibenzo p dioxin,Tetrachlorodibenzo p dioxin
D000279 Administration, Cutaneous The application of suitable drug dosage forms to the skin for either local or systemic effects. Cutaneous Drug Administration,Dermal Drug Administration,Drug Administration, Dermal,Percutaneous Administration,Skin Drug Administration,Transcutaneous Administration,Transdermal Administration,Administration, Dermal,Administration, Transcutaneous,Administration, Transdermal,Cutaneous Administration,Cutaneous Administration, Drug,Dermal Administration,Drug Administration, Cutaneous,Skin Administration, Drug,Administration, Cutaneous Drug,Administration, Dermal Drug,Administration, Percutaneous,Administrations, Cutaneous,Administrations, Cutaneous Drug,Administrations, Dermal,Administrations, Dermal Drug,Administrations, Percutaneous,Administrations, Transcutaneous,Administrations, Transdermal,Cutaneous Administrations,Cutaneous Administrations, Drug,Cutaneous Drug Administrations,Dermal Administrations,Dermal Drug Administrations,Drug Administrations, Cutaneous,Drug Administrations, Dermal,Drug Skin Administrations,Percutaneous Administrations,Skin Administrations, Drug,Skin Drug Administrations,Transcutaneous Administrations,Transdermal Administrations
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012869 Skin Absorption Uptake of substances through the SKIN. Absorption, Skin,Intracutaneous Absorption,Intradermal Absorption,Percutaneous Absorption,Transcutaneous Absorption,Transdermal Absorption,Absorption, Intracutaneous,Absorption, Intradermal,Absorption, Percutaneous,Absorption, Transcutaneous,Absorption, Transdermal,Absorptions, Intracutaneous,Absorptions, Intradermal,Absorptions, Percutaneous,Absorptions, Skin,Absorptions, Transcutaneous,Absorptions, Transdermal,Intracutaneous Absorptions,Intradermal Absorptions,Percutaneous Absorptions,Skin Absorptions,Transcutaneous Absorptions,Transdermal Absorptions
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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