TY - JOUR
T1 - Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA)
AU - Tollefsen, Knut Erik
AU - Scholz, Stefan
AU - Cronin, Mark T.
AU - Edwards, Stephen W.
AU - de Knecht, Joop
AU - Crofton, Kevin
AU - Garcia-Reyero, Natalia
AU - Hartung, Thomas
AU - Worth, Andrew
AU - Patlewicz, Grace
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes.
AB - Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes.
KW - (Q)SAR
KW - Adverse outcome pathway (AOP)
KW - Cross species extrapolation
KW - High content screening (HCS)
KW - High throughput screening (HTS)
KW - Integrated approaches to testing and assessment (IATA)
KW - Read-across
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U2 - 10.1016/j.yrtph.2014.09.009
DO - 10.1016/j.yrtph.2014.09.009
M3 - Article
C2 - 25261300
AN - SCOPUS:84922433050
SN - 0273-2300
VL - 70
SP - 629
EP - 640
JO - Regulatory Toxicology and Pharmacology
JF - Regulatory Toxicology and Pharmacology
IS - 3
ER -