Document Detail


Species- and strain-dependent teratogenicity of methanol in rabbits and mice.
MedLine Citation:
PMID:  20955785     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Estimates of human risk for developmental toxicity of methanol (MeOH) are based on studies in rodents, which unlike humans use catalase to metabolize MeOH. Rabbits, like humans, may largely use alcohol dehydrogenase (ADH), and more accurately than rodents reflect primate MeOH and formic acid (FA) pharmacokinetic profiles. Here we show that New Zealand white rabbits and one strain of mouse (C3H) are resistant to MeOH teratogenicity, whereas C57BL/6J mice are susceptible. Neither rabbits nor mice were susceptible to the acute MeOH toxicity observed in humans. The strain-dependent teratological susceptibility in mice could not be explained by differences in MeOH or FA disposition, nor could the resistance of rabbits, which exhibited more prolonged FA accumulation, suggesting that different mechanisms underlie MeOH teratogenesis and the FA-mediated acute toxicity in humans. It is not clear if the human risk for MeOH developmental toxicity can be accurately estimated using sensitive rodent strains.
Authors:
J Nicole Sweeting; Michelle Siu; Michael J Wiley; Peter G Wells
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Publication Detail:
Type:  Journal Article     Date:  2010-10-16
Journal Detail:
Title:  Reproductive toxicology (Elmsford, N.Y.)     Volume:  31     ISSN:  1873-1708     ISO Abbreviation:  Reprod. Toxicol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-02-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803591     Medline TA:  Reprod Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  50-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2.
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