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IMPLEMENTED - Modulating Factors
Modulating factors are extrinsic or intrinsic variables that, while not a direct causal element of an AOP, influence the response to the perturbation(s) represented in the AOP. They can be factors that convey greater or lesser sensitivity, can result in more, or less, severe effects, can alter time to effect(s) etc. Modulating factors act on one or more key event relationships (KERs) along the pathway. While they do not alter the causal connection between a pair of events, they do affect the quantitative attributes of the response-response relationship between those KEs.  However, because neither response-response relationships, nor the effect of modulating factors are always precisely defined in quantitative terms, the description of a modulating factor in the KER descriptions can range from qualitative to quantitative. Regardless, modulating factors should be supported by specific scientific evidence that establishes their overall effect on a given KER, which can include non-adjacent KERs (for example, linking the molecular initiating event directly to the adverse outcome).

Modulating factors are viewed as important information to capture with regard to an AOP, as they can be critical for application and interpretation. However, to date very little information about relevant modulating factors has been captured in the KER descriptions. This is thought to be, in part, because the text field for modulating factors is embedded as a sub-field under the heading of “Quantitative Understanding”.  Given that “Quantitative Understanding” is a section that is often left blank in KER descriptions, moving “Known Modulating Factors” to a separate section, independent of the “Quantitative Understanding” may increase visibility and lead to more information about modulating factors being captured in the AOP-Wiki.

A feature is therefore desirable in the AOP-Wiki to improve the capture of relevant modulating factor information during AOP development and, in the long term, increase the utility of that information for AOP users.

This feature was implemented in release 2.5 of the AOP-Wiki, published on 17 July 2022.
I am co-leader of the OECD AOP-KB development group - if you have any suggestions for the AOP-Wiki, please let me know!

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