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Toxicokinetics of domoic acid in the fetal rat.
MedLine Citation:
PMID:  22306965     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 is known regarding DA toxicokinetics in the fetal unit during maternal-fetal transfer. Tissue distribution and toxicokinetics of DA were investigated in pregnant rats and their pups just prior to birth at gestational day 20. Pregnant Sprague Dawley rats were given an intravenous dose of 1.0mgDA/kg and samples of maternal plasma, fetal plasma, placenta, amniotic fluid and fetal brain were taken at intervals over 24h. Toxicokinetic parameters were determined using WinNonLin software analysis. Maternal plasma DA log concentration-time curves fit a two compartment pharmacokinetic profile, with alpha and beta half-lives of elimination of 26.9 and 297min, respectively. Placenta had a C(max) of 752ng/mL and a terminal half-life of 577min. Maternal-fetal transfer between the plasma compartments was 31% with a fetal plasma C(max) of 86ng/mL at 60min and terminal half-life of 553min. Amniotic fluid and fetal brain had overall averages of 27±12ng/mL and 8.12ng/g, respectively, and did not show evidence of elimination over 24h. The longer fetal retention of DA, particularly in amniotic fluid, indicates that the fetus may be continually re-exposed during gestation, which could potentially lead to a disease state even at small exposure dose. This has implications for the California sea lions (Zalophus californianus), which exhibits an epilepsy-like disease that arises months after DA producing blooms.
Authors:
Jennifer Maucher Fuquay; Noah Muha; Zhihong Wang; John S Ramsdell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-28
Journal Detail:
Title:  Toxicology     Volume:  -     ISSN:  1879-3185     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-2-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ireland Ltd.
Affiliation:
National Oceanographic and Atmospheric Administration, Center for Coastal Environmental Health and Biomolecular Research, 219 Fort Johnson Road, Charleston, SC 29412, USA.
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