• Adverse outcome pathways;
  • Agent-based models;
  • Cost-benefit analysis;
  • Key events dose-response framework;
  • Mechanistic effect models


The need for cost-effective risk assessment of chemicals is leading to the development of a reductionist paradigm that tries to assess impacts on humans and ecosystems from molecular changes. However, the biggest challenge for this paradigm comes from the emergence of properties that arise out of the interactions of the parts that are not included and yet which are key for assessing likely impacts. Although identifying key events and adverse outcome pathways can shed light on the involvement of important metabolic processes in toxicity, this does not mean that particular molecular initiating events are likely to be robust or accurate predictors of impacts that matter. There are even greater challenges for the new paradigm applied to ecological systems than to human health because of the need to link across more levels of biological organization. The present study argues for a predictive systems approach that makes the linkages through systems models in a mechanistic way that allows for emergence and that also has the potential for reducing the costs and use of animals in ecological risk assessments. Environ. Toxicol. Chem. 2012; 31: 2663–2671. © 2012 SETAC