Document Detail


Paradigm shift in toxicity testing and modeling.
MedLine Citation:
PMID:  22528508     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The limitations of traditional toxicity testing characterized by high-cost animal models with low-throughput readouts, inconsistent responses, ethical issues, and extrapolability to humans call for alternative strategies for chemical risk assessment. A new strategy using in vitro human cell-based assays has been designed to identify key toxicity pathways and molecular mechanisms leading to the prediction of an in vivo response. The emergence of quantitative high-throughput screening (qHTS) technology has proved to be an efficient way to decompose complex toxicological end points to specific pathways of targeted organs. In addition, qHTS has made a significant impact on computational toxicology in two aspects. First, the ease of mechanism of action identification brought about by in vitro assays has enhanced the simplicity and effectiveness of machine learning, and second, the high-throughput nature and high reproducibility of qHTS have greatly improved the data quality and increased the quantity of training datasets available for predictive model construction. In this review, the benefits of qHTS routinely used in the US Tox21 program will be highlighted. Quantitative structure-activity relationships models built on traditional in vivo data and new qHTS data will be compared and analyzed. In conjunction with the transition from the pilot phase to the production phase of the Tox21 program, more qHTS data will be made available that will enrich the data pool for predictive toxicology. It is perceivable that new in silico toxicity models based on high-quality qHTS data will achieve unprecedented reliability and robustness, thus becoming a valuable tool for risk assessment and drug discovery.
Authors:
Hongmao Sun; Menghang Xia; Christopher P Austin; Ruili Huang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Review     Date:  2012-04-20
Journal Detail:
Title:  The AAPS journal     Volume:  14     ISSN:  1550-7416     ISO Abbreviation:  AAPS J     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-10-26     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  101223209     Medline TA:  AAPS J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  473-80     Citation Subset:  IM    
Affiliation:
Department of Health and Human Services, NIH Chemical Genomics Center, National Institutes of Health, Bethesda, Maryland 20892-3370, USA. hongmao.sun@nih.gov
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MeSH Terms
Descriptor/Qualifier:
Models, Theoretical*
Toxicity Tests*
Grant Support
ID/Acronym/Agency:
Y2-ES-7020-01/ES/NIEHS NIH HHS
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