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The Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) on the Uptake, Distribution and Excretion of a Single Oral Dose of [11,12-³H]Retinyl Acetate and on the Vitamin A Status in the Rat^{1, 2,}

Helen Håkansson^* and Ulf G. Ahlborg^*,,

^* Department of Toxicology, Karolinska Institutet, S-104 01 Stockholm The National Institute of Environmental Medicine, S-104 01 Stockholm, Sweden

TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin, 10 µg/kg body weight, p.o.) was given to male Sprague-Dawley rats 4 d before the oral administration of a physiological dose of [11,12-³H]retinyl acetate (RA). The rats were kept in metabolic cages for up to 192 h after RA administration. Radioactivity and/or vitamin A were determined in tissues and excreta. TCDD-pretreated and control rats excreted 41 and 23%, respectively, of the radioactivity of RA during the 192 h after administration. In control animals, 30% of the radioactivity of RA entered the liver within 6 h, the stores reaching 42% after 192 h. Maximum storage in TCDD-treated rats was 13% and after 192 h only 9% of the dose remained. A lag period of 12–24 h preceded the TCDD-induced increase in renal (175–671%) and serum (85–145%) radioactivity. In TCDD-treated rats less radioactivity was found in the intestine (45–79% decrease) and adrenals (14–73% decrease). Relative to the total body content, significantly more radioactivity was found in the kidney, serum, testes and epididymis of TCDD-treated rats. The decrease in vitamin A content after TCDD-treatment was 39–53% in the liver, 19–67% in the intestine and 18–44% in the epididymis. The kidneys of TCDD-treated rats contained more vitamin A (3–30 times more). TCDD treatment initially increased (42%) and later decreased (40%) the vitamin A content in the thymus as compared to controls. Pretreatment with a single low dose of TCDD thus affects both storage and excretion of radioactivity from newly administered RA as well as the vitamin A content in several tissues.

KEY WORDS: • [11,12-³H]retinyl acetate • 2,3,7,8-tetrachlorodibenzo-p-dioxin • TCDD • vitamin A

¹ Supported by grants from the Swedish Work Environment Fund (84-0139), the Ekhaga foundation and by funds at the Karolinska Institute.

² Presented in part at the IUPHAR 9th International Congress of Pharmacology, London, 29 July–3 August, 1984.

Manuscript received 28 October 1985. Revision accepted 6 March 1985.

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