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Application of New Approach Methods for Invertebrate Risk Assessment
Citation:
LaLone, C. Application of New Approach Methods for Invertebrate Risk Assessment. SETAC North America 42nd Annual meeting, Portland, OR, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.16984777
Impact/Purpose:
Presentation to the SETAC North America 42nd Annual meeting November 2021. 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:
The regulatory landscape is shifting away from whole animal testing for decision-making and exploring the utility of new approach methods (NAMs), which include computational techniques 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 the majority of 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. Additionally, the US EPA SeqAPASS tool has been applied to describe the taxonomic domain of applicability for these AOPs, which defines how broadly key events and key event relationships may be extrapolated by evaluating protein conservation. These methods maximize the utility of existing toxicity and sequence data to understand knowledge gaps, 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. Further, 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: Application of New Approach Methods for Invertebrate Risk Assessment
LALONE_SETAC_PRESENTATION_MH.PDF (PDF, NA pp, 3826.44 KB, about PDF)