Placental transfer and fetal distribution of lead in mice after treatment with dithiocarbamates.
The distribution of i.v. administered lead (203Pb-acetate; 50 nmol/kg b.w.) was studied by means of autoradiography and impulse counting in pregnant C57BL mice (day 18) treated orally with dithiocarbamates. Diethyldithiocarbamate ( DEDTC ), disulfiram or thiram (2 X 1 mmol/kg b.w.) or vehicle ( gelatine ) alone, was given by gavage 2 h before and immediately after the injection of lead. All three dithiocarbamates, especially thiram, changed the distribution pattern of lead. Thiram and DEDTC had the greatest effect at 4 h after lead administration, disulfiram at 24 h. In the mother, most notably the brain concentration increased (70-fold for thiram at 4 h) while that of erythrocytes and skeleton decreased (50- and 4-fold, respectively). The total fetal concentration unexpectedly showed only a moderate increase (approximately 2-fold for thiram), which may be due partly to the low maternal plasma lead concentration. The partition within the fetal tissues was, however, changed by the dithiocarbamates in much the same way as in the mothers, e.g., the fetal brain of thiram treated animals had increased by a factor 15, while skeletal and blood concentrations were lowered compared to controls. In melanin containing structures of the maternal and fetal eyes a dramatic increase in lead concentration resulted from dithiocarbamate treatment (lead ions are known to bind to melanin in vitro). The pattern of changes in lead distribution caused by dithiocarbamates is consistent with the formation in the body of lipid soluble lead-dithiocarbamate complexes that pass biological barriers more easily than lead inorganic (to brain, fetus, melanocytes etc.), probably followed by a dissociation of the complexes in the tissues.
D000818:Animals; D004221:Disulfiram / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007854:Lead / Q000097:blood / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013859:Thiocarbamates / Q000494:pharmacology*; D013893:Thiram / Q000494:pharmacology; D014018:Tissue Distribution
D013859:Thiocarbamates; D013893:Thiram; D007854:Lead; D004050:Ditiocarb; D004221:Disulfiram