Toxicokinetics of domoic acid in the fetal rat

摘要: Domoic acid (DA) is a potent neurotoxin that has both marine wildlife and human health impacts, including developmental effects during prenatal exposure in rodent models. However, little known regarding DA toxicokinetics the fetal unit maternal-fetal transfer. Tissue distribution of were investigated pregnant rats their pups just prior to birth at gestational day 20. Pregnant Sprague Dawley given an intravenous dose 1.0 mg DA/kg samples maternal plasma, placenta, amniotic fluid brain taken intervals over 24 h. Toxicokinetic parameters determined using WinNonLin software analysis. Maternal plasma log concentration-time curves fit two compartment pharmacokinetic profile, with alpha beta half-lives elimination 26.9 297 min, respectively. Placenta had C(max) 752 ng/mL terminal half-life 577 min. Maternal-fetal transfer between compartments was 31% 86 60 min 553 Amniotic overall averages 27±12 8.12 ng/g, respectively, did not show evidence The longer retention DA, particularly fluid, indicates fetus may be continually re-exposed gestation, which could potentially lead disease state even small dose. This implications for California sea lions (Zalophus californianus), exhibit epilepsy-like arises months after producing blooms.