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Commentary on the role of maternal toxicity on developmental toxicity.
MedLine Citation:
PMID:  22706915     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Maternal mammalian toxicity impacts prenatal development, with general systemic maternal toxicity, from reduced weight gain to morbidity, causative for reduced fetal weights/litter and increased fetal variations (especially skeletal)/litter, but not, in the author's opinion, for increased fetal malformations, reduced litter sizes or full litter losses. Increased fetal malformations are likely due to exposure to specific chemicals which alter specific maternal functions at critical point(s) in pregnancy, typically exaggerated effects from higher doses by drugs under development with known, desired pharmacological effects. Malformations can also be from genetic/epigenetic alterations, specific altered proteins, molecular pathways, etc. Full litter losses are triggered by the mother and are rare in rats. Information to inform maternal (and developmental) toxicity includes ovarian corpora lutea counts, uterine implantation profile, degree of litter reduction (if present), timing and extent of maternal toxicity relative to those of adverse embryofetal effects, etc. The view of maternal toxicity as confounding results in in vivo developmental toxicity studies, worldwide concerns about increased research animal usage, increasing time, labor, costs, and new software and hardware sophistication all drive the interest in development, validation, and performance of in vitro/in silico assays. These assays are fast, inexpensive, responsive to animal use concerns and amenable to mechanistic questions. The strength of these in vitro/in silico assays is considered by many to be the absence of the maternal organism/placenta. These assays inform mechanism and hazard, but NOT risk. The Environmental Protection Agency currently estimates that these new assays are approximately 70% accurate versus the whole animal tests.
Authors:
Rochelle W Tyl
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Publication Detail:
Type:  Journal Article     Date:  2012-04-11
Journal Detail:
Title:  Birth defects research. Part B, Developmental and reproductive toxicology     Volume:  95     ISSN:  1542-9741     ISO Abbreviation:  Birth Defects Res. B Dev. Reprod. Toxicol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101155115     Medline TA:  Birth Defects Res B Dev Reprod Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  262-6     Citation Subset:  IM    
Copyright Information:
© 2012 Wiley Periodicals, Inc.
Affiliation:
Discovery and Analytical Sciences, RTI International, Research Triangle Park, NC. rwt@rti.org.
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