Disposition of polychlorinated dibenzo-p-dioxins, dibenzofurans, and non-ortho polychlorinated biphenyls in pregnant long evans rats and the transfer to offspring.
Pharmacokinetic properties of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDFs), and non-ortho biphenyls (PCBs) play a critical role in their relative toxicity. The present study examined the transfer of these chemicals to offspring and placenta. Pregnant Long Evans rats received 0.0 (control), 0.05, 0.2, 0.8, and 1.0 microg/kg of dioxin toxic equivalence (TEQ) by oral gavage on the 15th gestational day (GD 15), using a dosing mixture that contained 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), octachlorodibenzofuran (OCDF), 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) in ratios approximating that in food. Rats were euthanized on GD 16, GD 21, and postnatal day 4 (PND 4). The chemical concentrations in fetus, pup, placenta, and maternal liver, serum, and adipose tissue were determined using gas chromatography/high-resolution mass spectrometry. A dose-dependent increase in hepatic sequestration was seen with TCDD, PeCDD, 4-PeCDF, OCDF, PCB 126, and PCB 169, and the transfer to offspring was reduced at higher doses. 4-PeCDF, PeCDD and PCB 126 showed higher liver affinity than TCDD. TCDF, 1-PeCDF, and PCB 77 were metabolized rapidly. On GD 16, TCDD and the three PCBs reached equilibration between the fetus and placenta, but this did not occur with PeCDD and 4-PeCDF until GD 21, according to the lipid-based concentrations. Offspring compartments received more of the dosed compounds lactationally than transplacentally (7-28% versus 0.5-3%). The behavior of each congener was dose-dependent; therefore, extrapolation of high-dose experimental data should be used with caution.
Chen
C Y
CY
Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400, USA.
Hamm
J T
JT
Hass
J R
JR
Birnbaum
L S
LS
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics* / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000633:toxicity; D011108:Polymers / Q000493:pharmacokinetics* / Q000633:toxicity; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D014018:Tissue Distribution
D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D011108:Polymers; C016068:polychlorodibenzofuran; D011078:Polychlorinated Biphenyls