2,3,7,8-Tetrachlorodibenzo-p-dioxin in Pregnant Long Evans Rats: Disposition to Maternal and Embryo/Fetal Tissues

Prenatal exposue to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)interfereswith fetal development at doses lower than those causing overttoxicity in adult animals. In a multigeneration study (Murrayet al., 1979), female rats that were administered 0.01 µgTCDD/kg/day in their diet did not experience reduced fertility;however, reduced fertility was seen in the F₁ and F₂ generations.Exposure to TCDD during development produces alterations inthe reproductive system of the developing pups, such as delayedpuberty and reduced sperm counts in males (Mably et al., 1992a;Gray et al., 1995) and malformations in the external genitaliaof females (Gray and Ostby, 1995). Therefore, the objectivesof this study were to determine maternal and fetal tissue concentrationsof TCDD that are associated with the adverse reproductive effectsseen by Gray and co-workers. Pregnant Long Evans rats receiveda single oral dose of 1.15 µg [₃H]TCDD/kg on GestationDay (GD) 8 and maternal as well as fetal tissue concentrationsof TCDD were measured on GD9, GD16, and GD21. On GD9, the highestlevel of TCDD localized in the maternal liver (25.1% dose).In addition, the amount reaching all the embryos on GD9 was0.01% of the administered dose, which resulted in a concentrationof 0.02% dose/g . The amount of TCDD reaching the fetal compartment(fetuses + placentas) increased to 0.12% dose/tissue on GD16and 0.71% by GD21. The concentration of TCDD within the fetalcompartment (0.01% dose/g) on GD16 was comparable to that foundin the maternal blood and spleen. Concentrations of TCDD ina single embryo/fetus were 39.6, 18.1, and 22.1 pg/g on GD9,GD16, and GD21, respectively. Estimates of hepatic half-lifeof elimination in pregnant rats suggested that TCDD may be eliminatedfaster in pregnant LE rats. Therefore, measurements of biliaryelimination were made in pregnant and nonpregnant LE rats tocompare rates of metabolism; however, biliary elimination ofTCDD is not affected by pregnancy. In conclusion, this doseadministered during a critical period of organogenesis causesadverse effects on the developing reproductive system of rodents.This dose produced a body burden of 22.1 pg TCDD/g within asingle fetus on GD21. This indicates that low-level TCDD exposureduring the perinatal stage of life can produce adverse effectswithin the developing pups.