METABOLISM AND BIOCHEMICAL EFFECTS OF 3,3',4,4'-TETRACHLOROBIPHENYL IN PREGNANT AND FETAL RATS

The metabolism and distribution of a single oral dose of 25 mu mol C-1 4-labelled 3,3',4,4'-tetrachlorobiphenyl (C-14-TCB) were investigated in pregnant female Wistar rats and their fetuses. TCB was administered on day 13 of gestation and the elimination was followed for 7 days. N on-pregnant rats were treated similarly for comparison. Fecal eliminat ion of C-14-TCB derived radioactivity was significantly lower in pregn ant rats than in non-pregnant rats. The major metabolite found in adul t liver and plasma, placental tissue, whole fetuses and fetal plasma w as 3,3',4',5-tetrachloro-4-biphenylol (4-OH-TCB). Tissue levels (liver , abdominal fat, skin, skeletal muscle, kidney and plasma) of C-14-TCB -derived radioactivity declined by 65-85% over a 7-day period followin g administration in the adult animals. However, C-14-TCB-derived radio activity accumulated more than 100-fold in the fetuses over the same t ime period, and GC/MS analysis revealed that the fetal accumulation in radioactivity was due primarily to 4-OH-TCB, and not the parent compo und. On day 20 of gestation, concentrations of 4-OH-TCB were 14 times greater in fetal plasma than maternal plasma. Treatment with C-14-TCB significantly reduced plasma thyroxine levels by at least 28% up to 7 days after administration in non-pregnant animals and up to 4 days aft er administration in pregnant rats (31% decrease). By 7 days after adm inistration plasma thyroxine levels had returned to control levels in the TCB-treated pregnant rats. However, fetal plasma thyroxine levels were significantly decreased by 35% in fetuses from C-14-TCB-treated d ams 7 days after TCB administration. Hepatic microsomal ethoxyresorufi n-O-deethylase (EROD) activity was significantly induced in TCB-treate d darns relative to controls at 4 and 7 days after administration, whi le no EROD activity was detected in hepatic microsomes from control or TCB treated fetal rats at day 20 of gestation. These data suggest tha t hydroxylated metabolites of polychlorinated biphenyls may play a rol e in the development toxicity of these compounds.