TOXICOKINETICS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN FEMALE SPRAGUE-DAWLEY RATS INCLUDING PLACENTAL AND LACTATIONAL TRANSFER TO FETUSES AND NEONATES

The toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in virgin female Sprague-Dawley (S-D) rats, the effects of pregnancy, parturition, and lactation on the distribution and/or redistribution of TCDD, and placental and lactational transfer to fetuses and neonates were investigated. Doses of 5.6 mu g/kg of C-14-labeled TCDD were given iv either to virgin rats or to pregnant rats on Day 18 of gestation and 1 day postparturition, respectively. Virgin females were terminated on Day 1, 2, 4, 8, 16, or 32, pregnant rats on Day 1, 2, 4, or 8, after dosing to collect tissues. Two groups of neonates, which were born either to TCDD-treated or nontreated darns were cross-fostered beginning on the first day after birth to simulate exposure to TCDD either by lactational transfer only or by both placental and lactational transfer. Serum and 18 different tissues were collected from virgin rats to evaluate the kinetic profile of TCDD. Serum and tissue samples from liver, kidney, brown, and white adipose tissue were collected from pregnant and postparturition rats. Liver samples from fetuses and neonates were obtained on Gestational Days 19 and 20, or postnatally on Days 1 and 5. TCDD equivalents were calculated from measurement of radioactivity. The results show that the profile of TCDD distribution in virgin female rats was similar to that in male rats but that the concentration of TCDD in most tissues was higher in females than in males. The ratios of tissue and serum areas under the curve and the ratio of half-lives between females and males were very similar to the ratio of the LD50s between male and female S-D rats, suggesting that the small gender difference in the acute toxicity of TCDD was probably due to the difference in toxicokinetics alone. Pregnancy and parturition as well as lactation significantly altered the toxicokinetic profile of TCDD probably due to changing body composition during pregnancy and nursing. The results also indicated that TCDD was predominantly transferred to the offspring by lactation rather than via the placenta. This highly efficient lactational transfer of TCDD in rats implied that breast feeding of children by mothers can result in effective transfer of TCDD via mother's milk. (C) 1995 Society of Toxicology.