Use of adverse outcome pathways in chemical toxicity testing: potential advantages and limitations

ABSTRACT

Amid revolutionary changes in toxicity assessment brought about by increasing regulation of chemicals, adverse outcome pathways (AOPs) have emerged as a useful framework to assess adverse effect of chemicals using molecular level effect, which aid in setting environmental regulation policies. AOPs are biological maps that describe mechanisms linking molecular initiating event to adverse outcomes (AOs) at an individual level. Each AOP consists of a molecular initiating event, key events, and an AO. AOPs use molecular markers to predict endpoints currently used in risk assessment, promote alternatives to animal model-based test methods, and provide scientific explanations for the effects of chemical exposures. Moreover, AOPs enhance certainty in interpreting existing and new information. The application of AOPs in chemical toxicity testing will help shift the existing paradigm of chemical management based on apical endpoints toward active application of in silico and in vitro data.