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Unleashing the Influence of Invertebrates through Application of New Approach Methods
Citation:
LaLone, C. Unleashing the Influence of Invertebrates through Application of New Approach Methods. University of Minnesota Entomology Seminar, Duluth, MN, January 18, 2022. https://doi.org/10.23645/epacomptox.19376315
Impact/Purpose:
Presentation to the University of Minnesota Entomology Seminar January 2022. Many new methods are being developed to make greater use of existing toxicity data for understanding chemical safety. The focus in development of these approaches has been to reduce and/or replace animal testing, generally referring to vertebrate toxicity testing. However, the approaches being developed may also be applied more broadly and could be used to understand the effects of chemicals on invertebrates as well. In particular, there are methods that gather toxicity data from the published literature to understand how a chemical may adversely affect biological pathways in tested model organisms. This pathway knowledge can aid in understanding where research may be lacking for invertebrate species and help guide the development of screening assays that can capture the unique biology of invertebrates. Further, because few invertebrates are used as model organism for chemical risk assessment to protect the >1.25 million invertebrate species that have been described it is important to understand how broadly data generated can be extrapolated to other organisms. The US EPA SeqAPASS tool can be used to understand similarities and differences between species at the molecular level to predict chemical susceptibility for untested species. The tool has been applied to extrapolate toxicity knowledge in the context of pesticides. These approaches in combination can be used to advance the use of existing biology to inform invertebrate risk assessments for chemical safety.
Description:
Global regulation of chemicals is shifting away from whole animal toxicity testing for decision-making and exploring the utility of new approach methods (NAMs), which include computational techniques and high-throughput screening methods to understand chemical toxicity. Primarily these efforts have focused on reducing the use of vertebrate species in toxicity testing, however in certain contexts NAMs are equally applicable to enhancing knowledge pertaining to invertebrate risk assessment. It has been estimated that 97% of the ~1.25 million known species are invertebrates, with only a small subset of model invertebrates (e.g., daphnids, chironomids, Apis and Bombus bees) used for decision-making in regulatory toxicology. Therefore, it is important that the existing toxicity data for the few invertebrate model organisms are maximally exploited to protect the diversity of invertebrate species that are not tested, including beneficial pollinators. Fortunately, with decreased cost in sequencing genomes and increased efficiency and advocacy for generating quality sequence data for many invertebrate species there are NAMs that can be used to better understand the effects of chemicals across a broader range of species. For example, the adverse outcome pathway framework collects biological pathway knowledge from existing studies describing the causal linkages from molecular level perturbations through the various levels of biological organization to adverse outcomes at the individual or population relevant for risk assessment. The AOP framework has been applied to understand the biology relative to chemical and non-chemical stressors impacting the nicotinic acetylcholine receptor and ecdysone receptor, both key proteins involved in invertebrate physiology. The objective in developing AOPs is to identify upstream events, typically molecular level changes in the biology, that can be predictive of apical effects, therefore allowing decision-makers the ability to use molecular data to inform safety decisions. Additionally, the US EPA SeqAPASS tool has been applied to describe the taxonomic domain of applicability for these AOPs, which defines how broadly the describe biology may be extrapolated by evaluating protein conservation. These methods maximize the utility of existing toxicity and sequence data to understand knowledge gaps for future research, define unique invertebrate biology that may require different testing strategies than vertebrates, and to extrapolate existing knowledge from model species to untested species of concern. Development of case examples that unitize these approaches has allowed for the identification of the major strengths and challenges for application of these approaches for research and decision making. To further enhance methods for exploring chemical toxicity without historical whole animal testing, efforts are underway to develop invertebrate specific high-throughput transcriptomic methods that could aid in understanding the unique biological pathways impacted by chemicals in the environment. Together these NAMs provide opportunities to gain mechanistic insights for chemical risk assessment relative to invertebrates. The contents of this abstract neither constitute nor necessarily reflect US EPA policy.
URLs/Downloads:
DOI: Unleashing the Influence of Invertebrates through Application of New Approach Methods
LALONE_ENTOMOLOGY_SEMINAR.PDF (PDF, NA pp, 7133.882 KB, about PDF)