Document Detail


Application of computational toxicological approaches in human health risk assessment. I. A tiered surrogate approach.
MedLine Citation:
PMID:  22369873     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hazard identification and dose-response assessment for chemicals of concern found in various environmental media are typically based on epidemiological and/or animal toxicity data. However, human health risk assessments are often requested for many compounds found at contaminated sites throughout the US that have limited or no available toxicity information from either humans or animals. To address this issue, recent efforts have focused on expanding the use of structure-activity relationships (SAR) approaches to identify appropriate surrogates and/or predict toxicological phenotype(s) and associated adverse effect levels. A tiered surrogate approach (i.e., decision tree) based on three main types of surrogates (structural, metabolic, and toxicity-like) has been developed. To select the final surrogate chemical and its surrogate toxicity value(s), a weight-of-evidence approach based on the proposed decision tree is applied. In addition, a case study with actual toxicity data serves as the evaluation to support our tiered surrogate approach. Future work will include case studies demonstrating the utility of the surrogate approach under different scenarios for data-poor chemicals. In conclusion, our surrogate approach provides a reasonable starting point for identifying potential toxic effects, target organs, and/or modes-of-action, and for selecting surrogate chemicals from which to derive either reference or risk values.
Authors:
Nina Ching Yi Wang; Q Jay Zhao; Scott C Wesselkamper; Jason C Lambert; Dan Petersen; Janet K Hess-Wilson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-17
Journal Detail:
Title:  Regulatory toxicology and pharmacology : RTP     Volume:  -     ISSN:  1096-0295     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8214983     Medline TA:  Regul Toxicol Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
National Center for Environmental Assessment, US Environmental Protection Agency, 26 West Martin Luther King Drive, Cincinnati, OH 45268, United States.
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