News: March 2020

AOP News - March 2020

SAAOP NEWS

The Society for Advancement of Adverse Outcome Pathways had recent election for two open positions.  Dan Villeneuve was elected Vice President and Jason O’Brien was elected Councillor. 

AOPWiki News

• The JRC now has a contract in place to facilitate the transition to AOP-KB 2.0.  This contract will allow any needed updates and maintenance of the current AOPWiki, and it includes the deployment of a dedicated development and testing server that will serve as a test bed for changes prior to moving them to the production server.
• The EPA has hired a part time programmer to help with gardening activities on the AOPWiki.  Current efforts are focused on updating the status of all AOPs

Upcoming Meetings/Symposia/Workshops/Training on AOPs

• The QSAR 2020 meeting will be held in Durham North Carolina from June 8 -11.  And it includes a training session entitled “AOP Hands-on Training: Building the Foundation for Predictive Toxicology”.  https://www.ascctox.org/qsar2020/qsar-2020-program
• The Human Toxicology Project Consortium and Physicians Committee for Responsible Medicine will once again co-sponsor an ancillary session on AOPs at the Society of Toxicology’s (SOT) annual meeting in Anaheim, CA: What AOPs can do for you: an introduction and hands-on experience, Hilton Anaheim, 4:45pm - 6:45pm, Mar 16, 2020.

Past Meetings/Symposia/Workshops/Training on AOPs

• An AOP training was held on 25 Feb 2020 at the US FDA as part of an internal in-person and webinar series on NAMs. About 70 FDA scientists participated. 
• An AOP-Wiki and AOP-DB training for ORD AOP Research Area contributors was held November 15^th, 2019, in conjunction with the yearly AOP-Knowledgebase meeting in Research Triangle Park, NC.
• Chemical Watch’s CHCS Training “Advanced Toxicology” Module 11 (March 4, 2020) will provide advanced training day in toxicology that includes the use of AOPs in interpreting data when there is a toxicological concern.   https://www.chcs.org.uk/event-3576429
• Also see links below for online training sites

WebNews

ChemicalWatch published two articles about AOPs in 2019

• In July 2019, ChemicalWatch published an article about the AOP Framework Study facilitated by the JRC.
  • https://chemicalwatch.com/79660/jrc-launches-adverse-outcome-pathway-survey
• In April 2019, ChemicalWatch published an article on how scientists from US EPA and Environment and Climate Change Canada have networked existing adverse outcome pathways (AOPs) to reveal thousands of potential new toxicity mechanisms.
  • https://chemicalwatch.com/76274/aop-knowledge-base-reveals-thousands-of-possible-toxicity-mechanisms

The Food Packaging Forum published a short note about the ChemicalWatch report on JRC’s AOP Survey https://www.foodpackagingforum.org/news/survey-on-adverse-outcome-pathways

OECD NEWS  (Contact:  Magda Sachana Magdalini.SACHANA@oecd.org )

AOP developers are encouraged to submit their AOPs to be considered in the OECD AOP Programme. Here is a link to the form to submit an AOP Project proposal.

The AOP workplan is updated in June and December of every year

The OECD released three webinar video recordings on Adverse Outcome Pathways:

1)  Adverse Outcome Pathways Framework, 30 April 2019

This first webinar on Adverse Outcome Pathways (AOPs) discussed the Adverse Outcome Pathway (AOP) framework. The AOP framework is a collaborative tool that applies an innovative approach for collecting mechanistic knowledge from various sources that can eventually support chemical safety assessment.

2)    Adverse Outcome Pathways: Assembling and evaluating weight of evidence and quantitative understanding - 15 January 2020

This second webinar on Adverse Outcome Pathways (AOPs) focused on the importance of weight of evidence in the process of developing AOPs, the types and lines of evidences assembled, examples demonstrating the lines of evidence and understanding why quantitative AOPs are developed. The AOP framework is a collaborative tool that applies an innovative approach for collecting mechanistic knowledge from various sources that can eventually support chemical safety assessment.

3)  Adverse Outcome Knowledge Base (AOP-KB) and AOP developing tips - 30 January 2020

The third webinar on Adverse Outcome Pathways (AOPs) focused on the core information and telecommunication technologies applications that were built to support AOP development, management, and dissemination. Tools and technical tips to facilitate scientific knowledge assembly and evaluations were also presented. The AOP framework implements a collaborative and innovative approach for collecting mechanistic knowledge from various sources that can eventually support chemical safety assessment.

Link to all the presentations:

• https://www.oecd.org/chemicalsafety/testing/webinars-on-testing-and-assessment-methodologies.htm

New AOPs published by OECD:  Following Joint Meeting declassification, seven AOPs were published in July 2019 on the OECD Series on Adverse Outcome Pathways.

JRC AOP Framework Analysis

The JRC has launched an AOP Framework study, which will analyse the framework's suitability to address regulatory priorities and support regulatory processes and decision-making. The focus of the study will be the AOP users, i.e. regulatory toxicologists, risk assessors and risk managers. An online survey will help to identify ca. 75 suitable telephone interviewees, from which 10-15 stakeholders will be selected to form a focus group. The focus group will then examine the study in-depth (on-site, with advanced ethnological methods) to arrive at observations and suggestions to adapt the framework to best meet stakeholder needs. The results of the study will be available by February 2020

 

IMPORTANT LINKS   

• 2019 AOP-Wiki On-Line Training

• Online courses developed to promote knowledge of and participation in the AOP process, including submissions to the AOP Wiki. The courses are freely available to any and everyone. Contact Kate Willett <kwillett@humanesociety.org>
  • https://humantoxicologyproject.org/about-pathways-2/aop-online-course/

• 2019  SEATAC (YouTubes) on AOP Development and Application
  • Part 1 - https://www.youtube.com/watch?v=EBTWgyzYUCc
  • Part 2 - https://www.youtube.com/watch?v=FM5VdlnrRKg

 

• 2016  AOP Learning Channel (YouTube)
  • https://www.youtube.com/channel/UCeP-bYPc1CRD3Ieaqrl-ysg

• 2016 SOT  Online AOP Continuing Education Course.
  • The following is a link to an SOT Continuing Education Course entitled “Adverse Outcome Pathway (AOP) Development and Evaluation” from the 2016 SOT meeting. Slides and audio are available at the following link (go to this link and then search for “adverse”)
  • http://www.toxicology.org/education/ce/onlineCourses.asp#courses

• OECD
  • AOP EAGMST Project
    • http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm
  • AOP Guidance Document
    • http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono(2013)6&doclanguage=en
  • AOP User’s handbook
    • https://www.oecd-ilibrary.org/environment/users-handbook-supplement-to-the-guidance-document-for-developing-and-assessing-adverse-outcome-pathways_5jlv1m9d1g32-en
  • e AOP Portal
    • https://aopkb.oecd.org/search.ashx

• AOP Learning
  • https://learning.aopkb.org/

• Adverse Outcome Pathway Knowledge Base (AOP-KB)
  • https://aopkb.oecd.org/background.html

• ERDC’s AOP Xplorer
  • http://apps.cytoscape.org/apps/aopxplorer
  • http://datasciburgoon.github.io/aopxplorer

PUBLICATIONS - Reports

• In 2016 ECETOC published a guidance document on application of AOPS to endocrine systems (Techinical Report 128)
  • http://www.ecetoc.org/publication/technical-report-no-128-guidance-assessment-application-adverse-outcome-pathways-aops-relevant-endocrine-system/
• ECETOC published Technical Report 122 on the current scientific understanding of the `lung overload` hypothesis which contains section on AOPs for lung tumors in rats and mice
  • Summary - http://www.ecetoc.org/report2/summary-3/
  • AOPS: http://www.ecetoc.org/report2/species-differences-and-mechanisms-of-lung-tumour-formation-in-rats/adverse-outcome-pathway/

PUBLICATIONS - Peer Reviewed Papers

1. Jeong J, Choi J. Development of AOP relevant to microplastics based on toxicity mechanisms of chemical additives using ToxCast™ and deep learning models combined approach. Environ Int. 2020 Feb 17;137:105557. doi: 10.1016/j.envint.2020.105557. [Epub ahead of print] PubMed PMID: 32078872.
2. Vinken M, Kramer N, Allen TEH, Hoffmans Y, Thatcher N, Levorato S, Traussnig H, Schulte S, Boobis A, Thiel A, Rietjens IMCM. The use of adverse outcome pathways in the safety evaluation of food additives. Arch Toxicol. 2020 Feb 17. doi: 10.1007/s00204-020-02670-0. [Epub ahead of print] PubMed PMID: 32065296.
3. Draskau, M. K., Spiller, C. M., Boberg, J., Bowles, J., & Svingen, T. (2020). Developmental biology meets toxicology: contributing reproductive mechanisms to build Adverse Outcome Pathways. Molecular Human Reproduction. https://doi.org/10.1093/molehr/gaaa001
4. Saili KS, Franzosa JA, Baker NC, Ellis-Hutchings RG, Settivari RS, Carney EW, Spencer R, Zurlinden TJ, Kleinstreuer NC, Li S, Xia M, Knudsen TB. Systems Modeling of Developmental Vascular Toxicity. Curr Opin Toxicol. 2019 Jun 1;15(1):55-63. doi: 10.1016/j.cotox.2019.04.004. PubMed PMID: 32030360; PubMed Central PMCID: PMC7004230.
5. Wheeldon RP, Bernacki DT, Dertinger SD, Bryce SM, Bemis JC, Johnson GE. Benchmark Dose Analysis of DNA Damage Biomarker Responses Provides Compound Potency and Adverse Outcome Pathway Information for the Topoisomerase II Inhibitor Class of Compounds. Environ Mol Mutagen. 2020 Jan 25. doi: 10.1002/em.22360. [Epub ahead of print] PubMed PMID: 31983063.
6. Ankley GT, Blackwell BR, Cavallin JE, Doering JA, Feifarek DJ, Jensen KM, Kahl MD, LaLone CA, Poole ST, Randolph EC, Saari TW, Villeneuve DL. Adverse Outcome Pathway Network-Based Assessment of the Interactive Effects of an Androgen Receptor Agonist and an Aromatase Inhibitor on Fish Endocrine Function. Environ Toxicol Chem. 2020 Jan 21. doi: 10.1002/etc.4668. [Epub ahead of print] PubMed PMID: 31965587.
7. Margiotta-Casaluci L, Dusza H, Moreira I, Winter MJ, Prior H. Development of an adverse outcome pathway (AOP) for cardiotoxicity mediated by the blockade of L-type calcium channels. J Pharmacol Toxicol Methods. 2019 Sep - Oct;99:106595. doi: 10.1016/j.vascn.2019.05.102. Epub 2019 Oct 17. PubMed PMID: 31962999.
8. Kam M, Spiller CM, Boberg J, Bowles J, Svingen T. Developmental biology meets toxicology: contributing reproductive mechanisms to build Adverse Outcome Pathways. Mol Hum Reprod. 2020 Jan 16. pii: gaaa001. doi: 10.1093/molehr/gaaa001. [Epub ahead of print] PubMed PMID: 31943113.
9. Sasaki JC, Allemang A, Bryce SM, Custer L, Dearfield KL, Dietz Y, Elhajouji A, Escobar PA, Fornace AJ Jr, Froetschl R, Galloway S, Hemmann U, Hendriks G, Li HH, Luijten M, Ouedraogo G, Peel L, Pfuhler S, Roberts D, Thybaud V, van Benthem J, Yauk CL, Schuler M. Application of the Adverse Outcome Pathway (AOP) Framework to Genotoxic Modes of Action (MOA). Environ Mol Mutagen. 2020 Environ. Molec Mutagen, 61(1), 114-134. PubMed PMID: 31603995.
10. Rugard M, Coumoul X, Carvaillo JC, Barouki R, Audouze K. Deciphering adverse outcome pathway network linked to Bisphenol F using text mining and systems toxicology approaches. Toxicol Sci. 2019 Oct 9. pii: kfz214. doi: 10.1093/toxsci/kfz214. [Epub ahead of print] PubMed PMID: 31596483.
11. Noyes PD, Friedman KP, Browne P, Haselman JT, Gilbert ME, Hornung MW, Barone S Jr, Crofton KM, Laws SC, Stoker TE, Simmons SO, Tietge JE, Degitz SJ. Evaluating  Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches. Environ Health Perspect. 2019 Sep;127(9):95001. doi: 10.1289/EHP5297. Epub 2019 Sep 5. PubMed PMID: 31487205.
12. Spinu N, Bal-Price A, Cronin MTD, Enoch SJ, Madden JC, Worth AP. Development and analysis of an adverse outcome pathway network for human neurotoxicity. Arch  Toxicol. 2019 Oct;93(10):2759-2772. doi: 10.1007/s00204-019-02551-1. Epub 2019 Aug 23. PubMed PMID: 31444508.
13. Hines DE, Conolly RB, Jarabek AM. A Quantitative Source-to-Outcome Case Study To Demonstrate the Integration of Human Health and Ecological End Points Using the Aggregate Exposure Pathway and Adverse Outcome Pathway Frameworks. Environ Sci Technol. 2019 Sep 17;53(18):11002-11012. doi: 10.1021/acs.est.9b04639. Epub 2019 Sep 3. PubMed PMID: 31436975.
14.  Corsi SR, De Cicco LA, Villeneuve DL, Blackwell BR, Fay KA, Ankley GT, Baldwin AK. Prioritizing chemicals of ecological concern in Great Lakes tributaries using high-throughput screening data and adverse outcome pathways. Sci Total Environ. 2019 Oct 10;686:995-1009. doi: 10.1016/j.scitotenv.2019.05.457. Epub 2019 Jun 5.  PubMed PMID: 31412529.
15. Hill Iii T, Conolly RB. Development of a novel AOP for Cyp2F2-mediated Lung Cancer in Mice. Toxicol Sci. 2019 Aug 12. pii: kfz185. doi: 10.1093/toxsci/kfz185. [Epub ahead of print] PubMed PMID: 31407013.
16. Aguayo-Orozco A, Audouze K, Siggaard T, Barouki R, Brunak S, Taboureau O. sAOP: Linking chemical stressors to Adverse Outcomes Pathway Networks. Bioinformatics. 2019 Jul 22. pii: btz570. doi: 10.1093/bioinformatics/btz570. [Epub ahead of print] PubMed PMID: 31329252.
17. Arzuaga X, Walker T, Yost EE, Radke EG, Hotchkiss AK. Use of the Adverse Outcome Pathway (AOP) framework to evaluate species concordance and human relevance of Dibutyl phthalate (DBP)-induced male reproductive toxicity. Reprod Toxicol. 2019 Jun 28. pii: S0890-6238(19)30069-3. doi: 10.1016/j.reprotox.2019.06.009. [Epub ahead of print] Review. PubMed PMID: 31260805.
18. Perkins EJ, Ashauer R, Burgoon L, Conolly R, Landesmann B, Mackay C, Murphy CA, Pollesch N, Wheeler JR, Zupanic A, Scholz S. Building and Applying Quantitative Adverse Outcome Pathway Models for Chemical Hazard and Risk Assessment. Environ Toxicol Chem. 2019 Sep;38(9):1850-1865. doi: 10.1002/etc.4505. Epub 2019 Aug 8. Review. PubMed PMID: 31127958.
19. Jeong J, Garcia-Reyero N, Burgoon L, Perkins E, Park T, Kim C, Roh JY, Choi J. Development of Adverse Outcome Pathway for PPARγ Antagonism Leading to Pulmonary Fibrosis and Chemical Selection for Its Validation: ToxCast Database and a Deep Learning Artificial Neural Network Model-Based Approach. Chem Res Toxicol. 2019 Jun 17;32(6):1212-1222. doi: 10.1021/acs.chemrestox.9b00040. Epub 2019 Jun 7. PubMed PMID: 31074622.
20. McMinn B, Duval AL, Sayes CM. An Adverse Outcome Pathway Linking Organohalogen Exposure to Mitochondrial Disease. J Toxicol. 2019 Apr 1;2019:9246495. doi: 10.1155/2019/9246495. eCollection 2019. PubMed PMID: 31057609; PubMed Central PMCID: PMC6463576.
21. Hong H, Dooley KE, Starbird LE, Francis HW, Farley JE. Adverse outcome pathway for aminoglycoside ototoxicity in drug-resistant tuberculosis treatment.  Arch Toxicol. 2019 May;93(5):1385-1399. doi: 10.1007/s00204-019-02407-8. Epub 2019 Apr 8. PubMed PMID: 30963202; PubMed Central PMCID: PMC6667179.
22. Coady K, Browne P, Embry M, Hill T, Leinala E, Steeger T, Maślankiewicz L, Hutchinson T. When Are Adverse Outcome Pathways and Associated Assays "Fit for Purpose" for Regulatory Decision-Making and Management of Chemicals? Integr Environ Assess Manag. 2019 Jul;15(4):633-647. doi: 10.1002/ieam.4153. Epub 2019 Jul 17. PubMed PMID: 30908812.
23. Song, Y., Xie, L., Lee, Y., Brede, D.A., Lyne, F., Kassaye, Y., Thaulow, J., Caldwell, G., Salbu, B., Tollefsen, K.E., 2020. Integrative assessment of low-dose gamma radiation effects on Daphnia magna reproduction: Toxicity pathway assembly and AOP development. Science of The Total Environment 705, 135912. doi: 10.1016/j.scitotenv.2019.135912. Epub 2019 Dec 5. PubMed PMID: 31846819.