Transplacental and lactational transfer of p,p'-DDE in Sprague-Dawley rats.
p,p'-DDE (hereafter DDE), a persistent metabolite of p,p'-DDT, is a widespread environmental contaminant that can induce antiandrogenic developmental effects in rats. Quantitative measurements of the transfer of DDE from pregnant or lactating dams to the fetus or suckling neonate were performed, and physiologically based pharmacokinetic (PBPK) models for the transplacental and lactational transfer of DDE were developed. Pregnant Sprague-Dawley rats were dosed by gavage in corn oil with either 10 or 100 mg DDE per kg body wt per day from Gestation Day (gd) 14 to 18. DDE was analyzed in several maternal tissues as well as in fetal and neonatal tissues from gd 15 to Postnatal Day (pnd) 21. Fetal DDE concentrations were about threefold lower than corresponding placental concentrations. By adopting a cross-fostering design, the contributions of transplacental and lactational transfer were compared. In the pup liver, where DDE was detectable in the 100 mg/kg groups on pnd 10, the lactationally exposed group had DDE concentrations about 50 times higher than those of the in utero only exposure group; the lactation only exposure groups had DDE tissue dose profiles very similar to those of the in utero plus lactation exposure groups, indicating that the lactational route is far more important than the in utero route quantitatively. The PBPK models postulated initial absorption of DDE into both the blood circulation and lymphatic system with the primary storage sites being maternal and neonatal adipose tissues. Mobilization of DDE from its storage sites is postulated to occur via its association with mobilized fatty acids and lipoproteins. The results provide an overall framework for evaluating the tissue dosimetry of DDE and for understanding how maternal exposure to DDE could affect perinatal sexual development in utero or in the early postnatal period.
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Chemical Industry Institute of Toxicology, 6 Davis Drive, Research Triangle Park, North Carolina, 27709-2137, USA.
Gazi
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Archibeque-Engle
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Casanova
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Conolly
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Heck
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D000273:Adipose Tissue / Q000254:growth & development / Q000378:metabolism; D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000254:growth & development / Q000378:metabolism*; D001822:Body Burden; D001835:Body Weight; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D003198:Computer Simulation; D003633:Dichlorodiphenyl Dichloroethylene / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D005865:Gestational Age; D007774:Lactation / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D003633:Dichlorodiphenyl Dichloroethylene