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Hydroxylated polychlorinated biphenyls: placental transfer and effects on thyroxine in the foetal mouse.

作者信息

Sinjari T, Darnerud P O

机构信息

Department of Pharmaceutical Biosciences, Uppsala University, Sweden.

出版信息

Xenobiotica. 1998 Jan;28(1):21-30. doi: 10.1080/004982598239722.

DOI:10.1080/004982598239722
PMID:9493316
Abstract
  1. At day 17 of pregnancy, 1 day after maternal intravenous administration (5-50 mumol/kg body wt) of 4-OH-3,5,3',4'-tetrachlorobiphenyl (4-OH-TCB; a CB-77 metabolite), a limited dose-dependent decrease was found both in foetal and maternal total thyroxine (T4) levels (76-81% of control at 50 mumol/kg). Similarly, a 50 mumol/kg dose of a 4-OH-3,5,2',3',4'-pentachlorobiphenyl (4-OH-PeCB1) decreased total T4 levels, whereas 4-OH-2,3,5,3',4'-pentachlorobiphenyl (4-OH-PeCB2) showed no clear effect (both 4-OH-pentaCBs are CB-105 metabolites). Earlier administration (gestation day 10 or 13) of the 4-OH-PCBs had no effect on total T4 at day 17. 2. Placental transfer of 14C-4-OH-TCB to the foetal compartment was dose-related and accumulated mainly in foetal plasma at levels 2-fold those in the maternal plasma at the dose interval 0.5-5.0 mumol/kg body wt, whereas at higher doses (20 and 50 mumol/kg body wt) the foetal and maternal plasma levels were similar. A break-point in the foetal dose/plasma concentration curve at 5.0 mumol/kg indicates saturation of a high-affinity ligand binding above this dose. 3. There was an extensive accumulation of radioactivity in the maternal liver after 14C-4-OH-TCB administration (20-30% of the administered dose). In spite of this the investigated compounds resulted in a small or no effect on EROD/MROD activity in maternal liver and these enzyme activities were not detectable in either exposed or control foetal liver.
摘要

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