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

Abstract

1. At day 17 of pregnancy, 1 day after maternal intravenous administration (5-50 μmol/kg body wt) of 4-OH-3,5,3',4'-tetrachlorobiph enyl (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 μmol/kg). Similarly, a 50 μmol/kg dose of a 4-OH-3,5,2',3',4'-pentachlorobiph enyl (4-OH-PeCB1) decreased total T4 levels, whereas 4-OH-2,3,5,3',4'-pentachlorobiph enyl (4-OH-PeCB2) showed no clear effect (both 4-OH-pentaCBsare 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 accumulatedmainly in foetal plasma at levels 2-fold those in the maternal plasma at the dose interval 0.5-5.0 μmol/kg body wt, whereas at higher doses (20 and 50 μmol/kg body wt) the foetal and maternal plasma levels were similar. A break-point in the foetal dose plasma concentration curve at 5.0 μmol/kg indicates saturation of a high-affinity ligand binding above this dose. 3. There was an extensive accumulationof 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.