Applying evidence-based methods to the development and use of adverse outcome pathways

Development of a putative adverse outcome pathway network for male rat reproductive tract abnormalities with specific considerations for the androgen sensitive window of development

“…While step-wise and meticulous, clear documentation of the key questions that drove the literature searches and clarity of literature relied upon (versus excluded) would have enhanced transparency in WoE underpinning these AOPs. Expanding the AOP framework to include standards for evidence identification has been suggested as a means to improve confidence ( De Vries et al, 2021 , Kleinstreuer et al, 2016 ; Leist et al., 2017); however the standards would have to be flexible to accommodate the iterative nature of the AOP development process and evergreen status of AOPs. Finally, inclusion of fit-for-purpose criteria may alleviate the evidence evaluation burden on AOP practitioners.…”

Probabilistic risk assessment – the keystone for the future of toxicology

“…For the identification of sources of uncertainty, uncertainty in our mechanistic understanding of the biological events that lead to human health effects needs to be identified by systematically mapping the peer-reviewed literature that has addressed this topic. Outcomes of recent workshops organized by the EBTC 6 ( de Vries et al, 2021 ; Tsaioun et al, in preparation ), relevant information from national and international bodies, especially the guidance and case studies of the OECD, and the opinions of leading scientists should be incorporated. The sources of uncertainties in NAM need to be identified using a similar approach, with a focus on literature and other information on the assessment of individual NAM and combinations of NAM in testing strategies.…”

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

“…Since KERs are putatively causallyrelated pairs of events, they are amenable to evaluation in a similar way to an exposure-outcome pair conventionally investigated in an EBM approach (i.e., SRs). A potential application of EBM in AOP development may therefore be as a series of KERs' SRs (De Vries et al, 2021).…”

“…, SRs). A potential application of EBM in AOP development may therefore be as a series of KERs’ SRs ( De Vries et al, 2021 ).…”

“…Evidence-Based Methodologies (EBMs), including systematic maps and systematic reviews (SRs), aim to help assemble and assess the current knowledge on a topic in an objective, comprehensive and transparent manner. Although the AOP development process does not currently explicitly require use of EBMs ( De Vries et al, 2021 ), efforts are ongoing to recommend AOP developers to document the most important aspects of their work, including the overall data identification, screening and evaluation strategy. EBMs adapted to AOP development, are desirable to increase transparency and promote the re-use of AOP components and their underlying data, and to inform the use for specific applications by the regulators.…”