Fetomaternal kinetics of 14C-trimethyltin

The mechanism of trimethyltin (TMT)-induced neuropathology remains unknown but likely relates to its time-course in the nervous system. To determine the pharmacokinetic profile of TMT in the fetomaternal unit, pregnant rats were injected on gestational day (GD) 17 with 7.0 mg/kg TMT plus 10 uCi 14C-TMT ip. Whole blood and plasma, cerebrum (CBR), cerebellum (CBE), and brainstem (BS) were sampled from mother and fetus/pup (f/p). Whole body saline perfusions of mother and f/p were performed independently to remove 14C contaminated blood. Whole blood total radioactivity showed f/p levels to be below maternal levels: at 4 hr, 42.6%, 24 hr, 54.2%, 96 hr, 64.8%. Litters were cross-fostered (CF) at birth with those from untreated mothers. Two weeks after treatment (postnatal day 10), pups exposed in utero (n=13, 2 litters) had whole blood 14C levels 13.9% that of their mothers. Untreated pups CF to treated mothers showed a blood concentration 1.8% of the dosed mother, indicating that TMT is transferred in milk. Radioactivity in maternal whole blood at 2 weeks was 49 +/- 11% (SEM) of peak (1 hr) levels. Only 2.5 +/- 0.2% of maternal whole blood radioactivity was present in plasma. 14C in urine accounted for 17.5 +/- 1.5% of the dose at 2 weeks (n=4). Both maternal and fetal brains contained about 2-4% as much radioactivity as found in maternal and fetal whole blood, respectively. TMT crosses the placenta, enters fetal blood and attains fetal brain levels that are equal to those found in maternal brain.