| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1998 Oxford University Press
other |
2,3,7,8-Tetrachlorodibenzo-p-dioxin in Pregnant Long Evans Rats: Disposition to Maternal and Embryo/Fetal Tissues1
*Curriculum in Toxicology, University of North Carolina Chapel Hill, North Carolina 27599-7270; and National Health and Environmental Effects Research Laboratory
Reproductive Toxicology Division, U.S. Environmental Protection Agency Research Triangle Park, North Carolina 27711
Experimental Toxicology Division, U.S. Environmental Protection Agency Research Triangle Park, North Carolina 27711
Received January 22, 1998; accepted June 3, 1998
Prenatal exposue to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)interferes with fetal development at doses lower than those causing overt toxicity in adult animals. In a multigeneration study (Murray et al., 1979), female rats that were administered 0.01 µg TCDD/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 in the reproductive system of the developing pups, such as delayed puberty and reduced sperm counts in males (Mably et al., 1992a; Gray et al., 1995) and malformations in the external genitalia of females (Gray and Ostby, 1995). Therefore, the objectives of this study were to determine maternal and fetal tissue concentrations of TCDD that are associated with the adverse reproductive effects seen by Gray and co-workers. Pregnant Long Evans rats received a single oral dose of 1.15 µg [3H]TCDD/kg on Gestation Day (GD) 8 and maternal as well as fetal tissue concentrations of TCDD were measured on GD9, GD16, and GD21. On GD9, the highest level of TCDD localized in the maternal liver (25.1% dose). In addition, the amount reaching all the embryos on GD9 was 0.01% of the administered dose, which resulted in a concentration of 0.02% dose/g . The amount of TCDD reaching the fetal compartment (fetuses + placentas) increased to 0.12% dose/tissue on GD16 and 0.71% by GD21. The concentration of TCDD within the fetal compartment (0.01% dose/g) on GD16 was comparable to that found in the maternal blood and spleen. Concentrations of TCDD in a single embryo/fetus were 39.6, 18.1, and 22.1 pg/g on GD9, GD16, and GD21, respectively. Estimates of hepatic half-life of elimination in pregnant rats suggested that TCDD may be eliminated faster in pregnant LE rats. Therefore, measurements of biliary elimination were made in pregnant and nonpregnant LE rats to compare rates of metabolism; however, biliary elimination of TCDD is not affected by pregnancy. In conclusion, this dose administered during a critical period of organogenesis causes adverse effects on the developing reproductive system of rodents. This dose produced a body burden of 22.1 pg TCDD/g within a single fetus on GD21. This indicates that low-level TCDD exposure during the perinatal stage of life can produce adverse effects within the developing pups.
Key Words: 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD; toxicokinetics; disposition; body burden; embryo; fetus.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. D. Mueller, J.-L. Vigne, M. Streich, M. K. Tee, L. Raio, E. Dreher, N. A. Bersinger, and R. N. Taylor 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Increases Glycodelin Gene and Protein Expression in Human Endometrium J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4809 - 4815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Emond, L. S. Birnbaum, and M. J. DeVito Physiologically Based Pharmacokinetic Model for Developmental Exposures to TCDD in the Rat Toxicol. Sci., July 1, 2004; 80(1): 115 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Salisbury and J. L. Marcinkiewicz In Utero and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and 2,3,4,7,8-Pentachlorodibenzofuran Reduces Growth and Disrupts Reproductive Parameters in Female Rats Biol Reprod, June 1, 2002; 66(6): 1621 - 1626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Hurst, B. Abbott, J. E. Schmid, and L. S. Birnbaum 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Disrupts Early Morphogenetic Events That Form the Lower Reproductive Tract in Female Rat Fetuses Toxicol. Sci., January 1, 2002; 65(1): 87 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Hurst, M. J. DeVito, and L. S. Birnbaum Tissue Disposition of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in Maternal and Developing Long-Evans Rats following Subchronic Exposure Toxicol. Sci., October 1, 2000; 57(2): 275 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Slezak, G. E. Hatch, M. J. DeVito, J. J. Diliberto, R. Slade, K. Crissman, E. Hassoun, and L. S. Birnbaum Oxidative Stress in Female B6C3F1 Mice following Acute and Subchronic Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Toxicol. Sci., April 1, 2000; 54(2): 390 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Hurst, M. J. DeVito, R. W. Setzer, and L. S. Birnbaum Acute Administration of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in Pregnant Long Evans Rats: Association of Measured Tissue Concentrations with Developmental Effects Toxicol. Sci., February 1, 2000; 53(2): 411 - 420. [Abstract] [Full Text] [PDF]
|
|