The disposition of 14C-trimethyltin in the pregnant rat and fetus.
Trimethyltin (TMT) is a potent neurotoxicant. For unknown reasons, age at exposure to TMT may dramatically influence the severity of TMT-induced neuropathology. We have demonstrated previously that radiolabel derived from [14C]-TMT given to pregnant dams on gestational day (GD) 17 is found in fetal brain and blood. The present study was designed to determine the distribution of radiolabel derived from [14C]-TMT to brain and other tissue in fetuses from dams dosed on either GD 12 or 17 with 7.0 mg/kg TMT chloride. Radioactivity in GD 12 and GD 17 maternal whole blood peaked 1 hour after IP treatment. Whole blood elimination half-lives were 12-15 days. Peak radiolabel concentrations in GD 12 maternal and fetal brain were only 11-30% of those from GD 17 animals, however, peak fetal brain concentrations of radiolabel were not different from their respective maternal brain concentrations. Radiolabel concentrations in liver, kidney, and adrenal of GD 17 dams were higher than those in corresponding GD 12 tissues. Combined urinary and fecal elimination of radiolabel for two weeks after dosing accounted for 31 and 22% of the GD 12 and 17 doses, respectively. It appears that gestational age influences the distribution and elimination of TMT in the rat.
Lipscomb
J C
JC
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Paule
M G
MG
Slikker
W
W
D000375:Aging; D000818:Animals; D002250:Carbon Radioisotopes; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014220:Trialkyltin Compounds / Q000493:pharmacokinetics*; D014298:Trimethyltin Compounds / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin