Comments for Aop:202
- All the suggestions made by Bette Meek have been addressed
- The AOP should be now very much in line with EAGMST recommendations.
- The strength of many relationship has been downgraded to moderate as suggested and in line with the handbook.
- Other changes were mainly cut and paste in different sections of the AOP.
Nathalie Delrue
On September 20, 2022 11:54
The AOP was submitted to the WNT and WPHA for endorsement on 22 April 2022. During this phase, Germany submitted comments which were addressed by the AOP authors to the satisfaction of Germany, who confirmed the endorsement of the AOP on 18 July 2022.
The attached document includes the comments sent by Germany to the authors of AOP 202 and the responses from the authors.
Nathalie Delrue
On October 05, 2021 10:40
Following the external review of AOP 202 in 2018 and discussion of EAGMST at its 11th meeting in 2018, Bette Meek (Canada) provided futher input to help progress towards approval of the AOP. The comments are available in the attachement.
Based on these comments several teleconferences have been organised. The author finalised the revisions of the AOP in December 2020 and indicated the following:
The revised AOP was reviewed by Bette Meek in February 2021, who concludes as follows:
I've been through the WOE calls, now, based on my previous comments and to verify consistency across KERs and the overall AOP for both biological plausibility and empirical support. I also contacted Andrea to clarify the reference to the downgrading of the confidence in some of the weight of evidence considerations to moderate, since they seemed not to have changed for the individual KERs for biological plausibility and empirical support since the revision that I considered previously (See attached query to Andrea during the earlier review and additional e-mails, on the revisions, below).
Though it was a bit difficult to directly compare the current version in the wiki with the external review “snapshot”, it appears that the confidence “call” for biological plausibility (b.p.) for the AOP overall has been downgraded from high to moderate; it was this “call” with which the reviewers were most concerned (due to limited direct evidence for each of the KERs). The rationales for the confidence calls appear also to have been expanded somewhat to emphasize limitations of the available experimental models to provide more direct evidence.
These revisions more than adequately address my observations below, as included (and highlighted) by Andrea in the attachment:
Confidence in the extent of the experimental evidence for the entire pathway is determined, based on that judged for each of the KERs. Given the paucity of direct experimental evidence for several of the KERs in utero for AOP 202 (i.e., infant leukemia) and principal reliance on analogous disease process, the rationale for the evidence for biological plausibility being considered “strong” is unclear and seemingly inconsistent with definitions and guidance provided in the Handbook.
This doesn’t undermine judgment regarding regulatory consideration of potential risk factors; it simply means that the extent of supporting evidence for the specific hypothesized pathway is limited (due largely to limitations of available experimental models).
The AOP is thus now submitted to EAGMST approval.
edited - October 05, 2021 10:40
Nathalie Delrue
On June 08, 2017 05:09
OECD Internal review - 2017. The comments from the internal reviewers (primary reviewer and one secondary reviewer) and responses from the authors are available in the attached document. The responses from the authors have been updated in October 2017 and report the actions taken following the internal review and the EAGMST meeting of June 2017.
In addition, this file also includes comments from the primary reviewer following the internal review final check (i.e. comments on the post EAGMST revision of the AOP). These comments are available in the last box of the file.
edited - December 05, 2017 11:40
Cataia Ives
On March 22, 2017 10:03
This AOP underwent OECD review prior to the launch of this version of the Wiki. To see those prior reviews, follow this link: https://aopwiki.org/wiki/index.php/Talk:Aop:202#tab=Formal_Reviews_Managed_by_the_OECD