Invertebrate model species in AOP development

In this chapter, we present the use of invertebrate model species in the development of adverse outcome pathways (AOPs), its challenges, and the current state of invertebrate toxicity studies. Invertebrates can contribute significantly towards the development of robust AOPs, providing many advantages over the use of vertebrate species. This includes a generally shorter life cycle allowing for chronic and full life cycle toxicity tests, and a wide array of powerful molecular genetic tools such as genome sequences, genomic engineering including gene knock-outs, and comprehensive bioinformatics databases. Currently, the most robustly developed invertebrate model species for toxicity testing include Daphnia, Caenorhabditis elegans, plus members of the Drosophila genus. The potential use of these and other invertebrate organisms for assessing chemical risk for most animals (including vertebrate species) is evaluated via a comparative phylogenetic approach to ecotoxicological testing, seeking to discover the evolutionary origins and distribution of toxicity pathways across the internal branches of the animal phylogeny. Comparative -omics data from cellular and developmental studies suggest a high degree of conservation in regulatory pathways in fly, worm and human. By comparing -omics studies between vertebrates and invertebrate species in toxicology, we begin to also discover coherence in pathway level responses, indicating potentially numerous overlapping responses to specific stressors, even across species that have different physiologies and ecological niches. At present, only a small number of invertebrate AOPs are informed by evidence. Perhaps the most robust of these is the Acetylcholinesterase inhibition (AChE) AOP for pesticides. We present a case study of using the AOP framework for risk assessment and discuss how the use of models, such as those using Dynamic Energy Budget theory linked to populations, can enhance the use of AOPs for understanding and predicting chemical risk.