Document Detail


Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish.
MedLine Citation:
PMID:  25456049     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth is an apical endpoint commonly assessed in chronic toxicity tests for which a replacement is desirable. Based on several criteria, we identified reduction in food intake to be a suitable key event for initiation of middle-out AOP development. To start exploring the upstream and downstream links of this key event, we developed three AOP case studies, for pyrethroids, selective serotonin reuptake inhibitors (SSRIs) and cadmium. Our analysis showed that the effect of pyrethroids and SSRIs on food intake is strongly linked to growth impairment, while cadmium causes a reduction in growth due to increased metabolic demands rather than changes in food intake. Locomotion impairment by pyrethroids is strongly linked to their effects on food intake and growth, while for SSRIs their direct influence on appetite may play a more important role. We further discuss which alternative tests could be used to inform on the predictive key events identified in the case studies. In conclusion, our work demonstrates how the AOP concept can be used in practice to assess critically the knowledge available for specific chronic toxicity cases and to identify existing knowledge gaps and potential alternative tests.
Authors:
Ksenia J Groh; Raquel N Carvalho; James K Chipman; Nancy D Denslow; Marlies Halder; Cheryl A Murphy; Dick Roelofs; Alexandra Rolaki; Kristin Schirmer; Karen H Watanabe
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Publication Detail:
Type:  REVIEW     Date:  2014-10-30
Journal Detail:
Title:  Chemosphere     Volume:  120C     ISSN:  1879-1298     ISO Abbreviation:  Chemosphere     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  0320657     Medline TA:  Chemosphere     Country:  -    
Other Details:
Languages:  ENG     Pagination:  778-792     Citation Subset:  -    
Copyright Information:
Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
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