NP/EFSA/PREV/2024/02 - Development of an AOP network for parkinsonian motor symptoms

Call reference: NP/EFSA/PREV/2024/02

Deadline to register interest: 14/06/2024 - 23.59 (CEST)

Background

Evidence from literature consistently indicates that a relationship exists between pesticide exposure and the onset of parkinsonian motor deficit. The mechanistic biological plausible link of this association was strengthened by the development of an adverse outcome pathway dealing with mitochondrial toxicity as intermediate upstream key event (Terron et al. 2018). This AOP was initially developed to provide a link between inhibition of the mitochondrial complex I and the parkisonian motor symptoms via selective loss of dopaminergic neurons. This initial AOP was endorsed by the OECD and is available in the AOP Wiki as AOP 3 (“Inhibition of the mitochondrial complex I of nigrostriatal neurons leads to parkinsonian motor deficits”) and is using rotenone and MPP+ as reference chemical stressors. The AOP 3 was further expanded (Delp. et al. 2021) with the inclusion of mitochondrial respiratory chain complex II (cII) and cIII inhibitors, and it was hypothesized that triggering their molecular initiating event (MIE) will cause mitochondrial dysfunction and might thereby trigger the same AO as cI inhibitors. Simultaneously, KE assays were implemented for the assessment of the KEs included in the AOP network. In addition, a Bayesian network to AOP quantification was developed for this AOP network (Tebby et al. 2022) and EFSA published an Scientific Opinion where, in addition to the AOP 3, a further MIE (Redox cycling of a chemical by mitochondria) was developed.

Objectives

1. To update the AOP wiki following the OECD AOP developmental guidance with the inclusion of the new MIE/KEs as reported in Delp. Et al 2021, Delp 2019 (for KE1/KE2), Van der Stel 2021 and in EFSA 2017. The empirical support and, where necessary, the biological plausibility for the interested key events relationship (KERs) should be included in the updated AOP network. A literature survey on additional investigations conducted using the AOP 3 as starting framework to complete the empirical support maybe necessary.
2. Expand the list of stressors, by inclusion of the new stressors as indicated in Delp et al. 2021 and 2019 and EFSA 2017
3. Update the list of methods as defined in Delp et al. 2021 for the characterization of the KE. The method description should be detailed and use standard or internationally recognized templates e.g. ToxTemplate
4. Include in the updated version of the AOP network the AOP quantification and uncertainty analysis thereof using the methodology and data included in Tebby et al. 2022.
5. Update the WOE tables and propose an updated WOE based on the newly provided empirical evidence.
6. Provide a list of reviewers and provide a review of the updated AOP network in line with AOP Guidance Document No 344 and agreed review principles
7. Follow the OECD review process (with EFSA support)

Selection criteria - technical and professional capacity:

Requirement 1: One lead expert with at least 8- years’ experience in the conduction of in vitro assays and proven experience in AOP development. Priority will be given to experts with proven experience in the test systems and methods described in Delp et al. 2021

Requirement 2: Two experts with at least 2 years’ experience in the conduction of in vitro assays and handling on in vitro derived data .

Procedure to register interest:

If you are interested in this procedure, please send an e-mail message within the deadline to EFSAprocurement [at] efsa.europa.eu (EFSAprocurement[at]efsa[dot]europa[dot]eu) quoting the reference of the procedure and specifying the following:

• your name/organisatio's name and full address;
• whether you participate as a physical person or an organisation/private company.

If you intend to apply in joint offer with partners. In this case, you must clearly identify each member of the joint offer and which partner is appointed as the lead partner. The composition of the partners in a joint offer cannot be changed once the invitation to tender letter has been sent.