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 redistributionof TCDD, and placental and lactational transfer to fetuses andneonates were investigated. Doses of 5.6 µg/kg of ¹⁴C-labeledTCDD were given iv either to virgin rats or to pregnant ratson 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 collecttissues. Two groups of neonates, which were born either to TCDD-treatedor nontreated dams were crossfostered beginning on the firstday after birth to simulate exposure to TCDD either by lactationaltransfer only or by both placental and lactatlonal transfer.Serum and 18 different tissues were collected from virgin ratsto evaluate the kinetic profile of TCDD. Serum and tissue samplesfrom liver, kidney, brown, and white adipose tissue were collectedfrom pregnant and postparturition rats. Liver samples from fetusesand neonates were obtained on Gestational Days 19 and 20, orpostnatally on Days 1 and 5. TCDD equivalents were caku latedfrom measurement of radioactivity. The results show that theprofile of TCDD distribution in virgin female rats similar tothat in male rats but that the concentration of TCDD in mosttissues was higher in females than in males. The ratios of tissueand serum areas under the curve and the ratio of half-livesbetween females and males were very similar to the ratio ofthe LD50s between male and female S-D rats, suggesting thatthe small gender difference in the acute toxicity of TCDD wasprobably due to the difference in toxicokinetics alone. Pregnancyand parturition as well as lactation significantly altered thetoxicokinetic profile of TCDD probably due to changing bodycomposition during pregnancy and nursing. The results also indicatedthat TCDD was predominantly transferred to the offspring bylactation rather than via the placenta. This highly efficientlactational transfer of TCDD in rats implied that breast feedingof children by mothers can result in effective transfer of TCDDvia mother's milk.