The adverse outcome pathway: A multifaceted framework supporting 21st century toxicology

Ankley, Gerald T.; Edwards, Stephen W.

doi:10.1016/j.cotox.2018.03.004

Cited by 97 publications

(60 citation statements)

References 47 publications

(57 reference statements)

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“…The combined use of lethal and sublethal endpoints is becoming increasingly common in ecotoxicological research due to the ability to integrate mechanistic data with higher level biological outcomes (Ankley and Edwards 2018). Thus we evaluated both molecular endpoints (metabolomics) and higher level endpoints directly related to fitness (survival and reproduction) in our assessment of pesticide toxicity to A .…”

Section: Discussionmentioning

confidence: 99%

Polyps of the Jellyfish Aurelia aurita Are Unaffected by Chronic Exposure to a Combination of Pesticides

Olguín-Jacobson

Pitt

Carroll

et al. 2020

Enviro Toxic and Chemistry

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Pesticides are a major contaminant in coastal waters and can cause adverse effects in marine invertebrates such as jellyfish. Most studies have investigated short‐term responses of organisms to unrealistically high concentrations of pesticides; however, chronic exposure to persistent low concentrations, which are more likely to occur in the environment, are rarely analyzed. We tested the response of polyps of the moon jellyfish Aurelia aurita to environmental concentrations of the herbicide atrazine and the insecticide chlorpyrifos, individually and in combination, over 9 wk. We hypothesized that exposure to individual pesticides would reduce rates of asexual reproduction and alter polyps' metabolite profiles, and that the results would be more severe when polyps were exposed to the combined pesticides. Polyps survived and reproduced (through budding) in all treatments, and no differences among treatments were observed. Proton nuclear magnetic resonance spectroscopy revealed no difference in profiles of polar metabolites of polyps exposed to the individual or combined pesticides. Our results suggest that A. aurita polyps are unaffected by chronic exposure to atrazine and chlorpyrifos at concentrations recommended as being protective by current Australian water quality guidelines. Environ Toxicol Chem 2020;39:1685–1692. © 2020 SETAC

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Section: Discussionmentioning

confidence: 99%

Polyps of the Jellyfish Aurelia aurita Are Unaffected by Chronic Exposure to a Combination of Pesticides

Olguín-Jacobson

Pitt

Carroll

et al. 2020

Enviro Toxic and Chemistry

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“…Putative or qualitative AOPs can guide toxicity testing strategies, inform prioritization of research by identifying knowledge gaps, aid in screening and prioritization of chemicals for further toxicity testing using animal models and guide the principles of decision matrices such as integrated approaches to testing and assessment (IATA) [19][20][21][22]. AOPs can support systematic review and integration of diverse multi-source and nonstandard data types, including data derived from in silico and in vitro assays that are not standard in the current risk assessment framework [23]. More importantly, putative or qualitative AOPs can inform design and development of targeted in vitro assays, identification of targeted biomarkers, providing the biological context for the interpretation and extrapolation of non-standard data to in vivo responses [6,19,24].…”

Section: Application Of Aops In Hhra Of Nanomaterialsmentioning

confidence: 99%

Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale

et al. 2020

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Toxicity testing and regulation of advanced materials at the nanoscale, i.e. nanosafety, is challenged by the growing number of nanomaterials and their property variants requiring assessment for potential human health impacts. The existing animal-reliant toxicity testing tools are onerous in terms of time and resources and are less and less in line with the international effort to reduce animal experiments. Thus, there is a need for faster, cheaper, sensitive and effective animal alternatives that are supported by mechanistic evidence. More importantly, there is an urgency for developing alternative testing strategies that help justify the strategic prioritization of testing or targeting the most apparent adverse outcomes, selection of specific endpoints and assays and identifying nanomaterials of high concern. The Adverse Outcome Pathway (AOP) framework is a systematic process that uses the available mechanistic information concerning a toxicological response and describes causal or mechanistic linkages between a molecular initiating event, a series of intermediate key events and the adverse outcome. The AOP framework provides pragmatic insights to promote the development of alternative testing strategies. This review will detail a brief overview of the AOP framework and its application to nanotoxicology, tools for developing AOPs and the role of toxicogenomics, and summarize various AOPs of relevance to inhalation toxicity of nanomaterials that are currently under various stages of development. The review also presents a network of AOPs derived from connecting all AOPs, which shows that several adverse outcomes induced by nanomaterials originate from a molecular initiating event that describes the interaction of nanomaterials with lung cells and involve similar intermediate key events. Finally, using the example of an established AOP for lung fibrosis, the review will discuss various in vitro tests available for assessing lung fibrosis and how the information can be used to support a tiered testing strategy for lung fibrosis. The AOPs and AOP network enable deeper understanding of mechanisms involved in inhalation toxicity of nanomaterials and provide a strategy for the development of alternative test

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“…Examples of this can be seen in Figs. 2,3,4,5 and 6. It is important to note that AOPs are not specific to, or defined by, any specific chemical, but rather represents a biologically plausible chain of events that can be triggered by chemical exposure (Ankley and Edwards 2018). In this Fig.…”

Section: The Adverse Outcome Pathway (Aop) Concept In Briefmentioning

confidence: 99%

Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals

et al. 2020

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Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause–effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difficult to assess the risks chemical exposures pose to a woman’s reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can affect female reproductive health. We have a special focus on effects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause–effect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This effort is an important step towards better safeguarding the reproductive health of all girls and women.

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The adverse outcome pathway: A multifaceted framework supporting 21st century toxicology

Cited by 97 publications

References 47 publications

Polyps of the Jellyfish Aurelia aurita Are Unaffected by Chronic Exposure to a Combination of Pesticides

Polyps of the Jellyfish Aurelia aurita Are Unaffected by Chronic Exposure to a Combination of Pesticides

Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale

Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals

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