Evidenced-Based Approaches to Support the Development of Endocrine-Mediated Adverse Outcome Pathways: Challenges and Opportunities

Audouze, Karine; Zgheib, Elias; Abass, Khaled; Baig, Asma; Forner-Piquer, Isabel; Holbech, Henrik; Knapen, Dries; Leonards, P.E.G.; Lupu, Diana; Palaniswamy, Saranya; Rautio, Arja; Sapounidou, Maria; Martin, Olwenn

doi:10.3389/ftox.2021.787017

Cited by 8 publications

(8 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We additionally provide auxiliary evidence for the association of KEs with inorganic cadmium in the directed AOP network. In future, integrative data-centric evidence-based approaches can be leveraged to expand the scope of existing AOPs, or develop novel AOPs, which can further enable the derivation of comprehensive and elaborate AOP networks [103][104][105][106][107]. Further experimentation is required to characterize the points-of-departure of cadmium toxicity and that will aid in strengthening chemical regulations, thereby advancing chemical exposome research.…”

Section: Discussionmentioning

confidence: 99%

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

Sahoo,

Chivukula,

Ramesh

et al. 2023

Preprint

View full text Add to dashboard Cite

Cadmium is a prominent toxic heavy metal that contaminates both terrestrial and aquatic environments. Owing to its high biological half-life and low excretion rates, cadmium causes a variety of adverse biological outcomes. Adverse outcome pathway (AOP) networks were envisioned to systematically capture toxicological information to enable risk assessment and chemical regulation. Here, we leveraged AOP-Wiki and integrated heterogeneous data from four other exposome-relevant resources to build the first AOP network relevant for inorganic cadmium-induced toxicity. From AOP-Wiki, we filtered 309 high confidence AOPs, identified 312 key events (KEs) associated with inorganic cadmium, and thereafter, curated 30 cadmium relevant AOPs (cadmium-AOPs), using a data-centric approach. By constructing the undirected AOP network, we identified a large connected component of 18 cadmium-AOPs. Further, we analyzed the directed network of 59 KEs and 82 key event relationships (KERs) in the largest component using graph-theoretic approaches. Subsequently, we mined published literature using artificial intelligence-based tools to provide auxiliary evidence of cadmium association for all KEs in the largest component. Finally, we performed case studies to verify the rationality of cadmium-induced toxicity in humans and aquatic species. Overall, cadmium-AOP network constructed in this study will aid ongoing research in systems toxicology and chemical exposome.

show abstract

Section: Discussionmentioning

confidence: 99%

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

Sahoo,

Chivukula,

Ramesh

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This way, an AOP spans multiple levels of biological organization and the content depends on the extent of biological information existing for the specific AOP. Hence, the AOP concept provides an almost fit-for-purpose framework for ED assessments as it i) defines an AO in an intact organisms, ii) it describes a mode-of-action, and iii) it establishes a biologically plausible link between the mode-of-action and the AO (Audouze et al, 2021).…”

Section: Using the Adverse Outcome Pathway Framework To Aid In Ed Ass...mentioning

confidence: 99%

Using alternative test methods to predict endocrine disruption and reproductive adverse outcomes: do we have enough knowledge?

Svingen

Schwartz

Rosenmai

et al. 2022

Environmental Pollution

View full text Add to dashboard Cite

“…The AOP framework provides a harmonized approach to describe a causal chain of events linking a molecular initiating event (MIE) to key events (KE) at different levels of biological organization, ultimately leading to an adverse outcome (AO) through defined key event relationships (KER) ( Ankley et al, 2010 ; Villeneuve et al, 2014 ; Ankley and Edwards, 2018 ). AOPs thus provide a structured format to summarise available evidence for, and confidence in, the causal links between MIEs and AOs; i.e., they are valuable tools for MoA analysis in ED assessment and for developing Integrated Approaches to Testing and Assessment (IATA) ( Browne et al, 2017 ; OECD, 2017 ; Audouze et al, 2021 ; Svingen et al, 2022 ; Bajard et al, 2023 ; Wiklund et al, 2023 ). Development of AOPs is currently overseen by the OECD’s Advisory Group on Emerging Science in Chemicals Assessment (ESCA) in collaboration with the Society for the Advancement of AOPs (SAAOP) and AOP Knowledge Base Coordination Group.…”

Section: Introductionmentioning

confidence: 99%

Building an adverse outcome pathway network for estrogen-, androgen- and steroidogenesis-mediated reproductive toxicity

Zilliacus,

Draskau,

Johansson

et al. 2024

Front. Toxicol.

View full text Add to dashboard Cite

Introduction: Adverse Outcome Pathways (AOPs) can support both testing and assessment of endocrine disruptors (EDs). There is, however, a need for further development of the AOP framework to improve its applicability in a regulatory context. Here we have inventoried the AOP-wiki to identify all existing AOPs related to mammalian reproductive toxicity arising from disruption to the estrogen, androgen, and steroidogenesis modalities. Core key events (KEs) shared between relevant AOPs were also identified to aid in further AOP network (AOPN) development.Methods: A systematic approach using two different methods was applied to screen and search the entire AOP-wiki library. An AOPN was visualized using Cytoscape. Manual refinement was performed to remove AOPS devoid of any KEs and/or KERs.Results: Fifty-eight AOPs relevant for mammalian reproductive toxicity were originally identified, with 42 AOPs included in the final AOPN. Several of the KEs and KE relationships (KERs) described similar events and were thus merged to optimize AOPN construction. Sixteen sub-networks related to effects on hormone levels or hormone activity, cancer outcomes, male and female reproductive systems, and overall effects on fertility and reproduction were identified within the AOPN. Twenty-six KEs and 11 KERs were identified as core blocks of knowledge in the AOPN, of which 19 core KEs are already included as parameters in current OECD and US EPA test guidelines.Discussion: The AOPN highlights knowledge gaps that can be targeted for further development of a more complete AOPN that can support the identification and assessment of EDs.

show abstract

Evidenced-Based Approaches to Support the Development of Endocrine-Mediated Adverse Outcome Pathways: Challenges and Opportunities

Cited by 8 publications

References 43 publications

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

Using alternative test methods to predict endocrine disruption and reproductive adverse outcomes: do we have enough knowledge?

Building an adverse outcome pathway network for estrogen-, androgen- and steroidogenesis-mediated reproductive toxicity

Contact Info

Product

Resources

About