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Terje Svingen, Daniel L. Villeneuve, Dries Knapen, Eleftheria Maria Panagiotou, Monica Kam Draskau, Pauliina Damdimopoulou, Jason M. O’Brien
The adverse outcome pathway (AOP) framework provides a practical means for organizing scientific knowledge that can be used to infer cause-effect relationships between stressor events and toxicity outcomes in intact organisms. It has reached wide acceptance as a tool to aid chemical safety assessment and regulatory toxicology by supporting a systematic way of predicting adverse health outcomes based on accumulated mechanistic knowledge. A major challenge for broader application of the AOP concept in regulatory toxicology, however, has been developing robust AOPs to a level where they are peer reviewed and accepted. This is because the amount of work required to substantiate the modular units of a complete AOP is considerable, to the point where it can take years from start to finish. To help alleviate this bottleneck, we propose a more pragmatic approach to AOP development whereby the focus becomes on smaller blocks. First, we argue that the key event relationship (KER) should be formally recognized as the core building block of knowledge assembly within the AOP knowledge base (AOP-KB), albeit framing them within full AOPs to ensure regulatory utility. Second, we argue that KERs should be developed using systematic review approaches, but only in cases where the underlying concept does not build on what is considered canonical knowledge. In cases where knowledge is considered canonical, rigorous systematic review approaches should not be required. It is our hope that these approaches will contribute to increasing the pace at which the AOP-KB is populated with AOPs with utility for chemical safety assessors and regulators.
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Svingen, T., Villeneuve, D. L., Knapen, D., Panagiotou, E. M., Draskau, M. K., Damdimopoulou, P., & O’Brien, J. M. (2021). A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation. Toxicological Sciences, 184(2), 183–190. https://doi.org/10.1093/toxsci/kfab113
Svingen, Terje, et al. "A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation." Toxicological Sciences, vol. 184, no. 2, 2021, pp. 183–190, https://doi.org/10.1093/toxsci/kfab113.
Svingen, Terje, Daniel L. Villeneuve, Dries Knapen, Eleftheria Maria Panagiotou, Monica Kam Draskau, Pauliina Damdimopoulou, and Jason M. O’Brien. "A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation." Toxicological Sciences 184, no. 2 (2021): 183–190. https://doi.org/10.1093/toxsci/kfab113.
Svingen T., Villeneuve D. L., Knapen D. [и др.] A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation // Toxicological Sciences. — 2021. — Vol. 184, № 2. — P. 183–190. — URL: https://doi.org/10.1093/toxsci/kfab113
@article{svingen2021pragmatic,
title = {{A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation}},
author = {Terje Svingen and Daniel L. Villeneuve and Dries Knapen and Eleftheria Maria Panagiotou and Monica Kam Draskau and Pauliina Damdimopoulou and Jason M. O’Brien},
journal = {Toxicological Sciences},
year = {2021},
volume = {184},
number = {2},
pages = {183--190},
doi = {10.1093/toxsci/kfab113},
url = {https://doi.org/10.1093/toxsci/kfab113}
}TY - JOUR AU - Svingen, Terje AU - Villeneuve, Daniel L. AU - Knapen, Dries AU - Panagiotou, Eleftheria Maria AU - Draskau, Monica Kam AU - Damdimopoulou, Pauliina AU - O’Brien, Jason M. TI - A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation JO - Toxicological Sciences VL - 184 IS - 2 SP - 183 EP - 190 PY - 2021 DA - 2021/09/15 DO - 10.1093/toxsci/kfab113 UR - https://doi.org/10.1093/toxsci/kfab113 ER -
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