AOP learning opportunities at SOT 2017

The Human Toxicology Project Consortium will once again co-sponsor an Adverse Outcome Pathway-training at the Society of Toxicology’s (SOT) annual meeting in Baltimore, Maryland. On Tuesday, March 14, from 5:00PM-7:00PM, registrants can take part in our Hands-On Seminar: Creating an Adverse Outcome Pathway in the AOP Wiki, which HTPC is co-sponsoring with the Physicians Committee for Responsible Medicine (PCRM).

At this seminar, participants will have a chance to deepen their understanding of the AOP Wiki (Version 2.0) and gain experience entering an Adverse Outcome Pathway.  Attendees will work through a case example in small groups.  In addition, participants will get a preview of an online course on AOPs and the AOP-Wiki that will soon be available here on the HTPC website.

Agenda:

5:00-5:20: International Efforts to Identify, Standardize, and Apply AOPs (Kristie Sullivan, PCRM)

5:20-6:00: A New Online Course on Adverse Outcome Pathways (Catherine Willett, HTPC)

6:00-7:00: The AOP Wiki 2.0: Demonstration and hands-on exercise (Stephen Edwards, US EPA)

The seminar will take place in the Constellation Ballroom A – Hyatt Regency Baltimore, 300 Light Street.  Please register in advance with Kristie Sullivan at PCRM: ksullivan@pcrm.org

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At this SOT gathering, HTPC is also once again co-sponsoring (along with the Center for Alternatives to Animal Testing [CAAT] and the Human Toxome Project) the well-regarded satellite meeting, Updates on Activities Related to 21st Century Toxicology and Related Efforts.  As always, the meeting will feature a number of invited presentations, but also leave time for an “open microphone” segment in which participants are welcome to give brief presentations on germane topics, with or without a few slides.  This satellite meeting takes place Thursday, March 16 from noon to 4:30PM at the Lord Baltimore Hotel.

The draft program is as follows:

12:30 Box lunch (for pre-registered participants) and welcome, Thomas Hartung (Johns Hopkins University)

13:00 Invited speakers (10 minute presentations each followed by 5 mins. of discussion)

  • ToxCast Update – Russell Thomas (US Environmental Protection Agency)
  • EDSP21 Update – Stanley Barone (US Environmental Protection Agency)
  • Tox21 Update – Richard Paules (US National Toxicology Program)
  • TT21C update – Rebecca Clewell (ScitoVision)
  • NICEATM Update – Nicole Kleinstreuer (NICEATM)
  • EU Tox-Risk Update – Robert van de Water (University of Tuebingen)
  • NAS Report on Using 21st Century Science to Improve Risk-Related Evaluations – TBD
  • Evidence-based Toxicology Update – Katya Tsaioun (EBT Johns Hopkins)
  • CAAT’s Read-across Initiative and Human Toxome-related Activity Update – Thomas Hartung (Johns Hopkins)
  • Human Toxicology Project Consortium Update – Catherine Willett (HTPC)

15:15 Open microphone for additional presentations and discussion

16:00 Adjourn

Box lunches will be available to those who have pre-registered. Contact Jamie DeRita.

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Also at this year’s SOT meeting, HTPC coordinator Catherine Willett will present a poster on HTPC’s soon-to-be-released online training course on adverse outcome pathways. Look for her poster, “Advancing the Development of Quality AOPs Submitted to OECD’s AOP Knowledge Base (AOP-KB) and the AOP-Wiki” during the Late Breaking Poster Session on Thursday, March 16, from 9:00AM to noon (late-breaking abstract #3441; Poster # P413).

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Human Toxicology Project Consortium at the Society of Toxicology meeting in New Orleans

You’ll find the Human Toxicology Project Consortium at the Society of Toxicology’s annual meeting in New Orleans next week – in the ToxExpo center, poster sessions, workshops, and seminars.

  • Visit HTPC’s informational booth at ToxExpo, booth #1704.
  • HTPC is co-sponsoring a “hands-on” seminar, “Creating an Adverse Outcome Pathway in the AOP Wiki,” on Tuesday, March 15, from 5-7PM in the Hilton Riverside.  More details about the seminar can be found here.
  • HTPC is also once again co-sponsoring and presenting at the annual SOT Satellite Meeting, Updates on Activities Related to 21st Century Toxicology and Related Efforts: Invited Presentations and Open Microphone, on Thursday, March 17, 12:30 PM to 4:00 PM, Hilton New Orleans Riverside, Jefferson Ballroom. As always, this informative meeting features a number of invited presentations, and also allows time for an “open microphone” segment in which participants are welcome to give brief presentations on germane topics.

The draft program is as follows:

12:30 PM—Box Lunch (for pre-registered participants) and Welcome by Thomas Hartung, Johns Hopkins University

1:00 PM—Invited Speakers (10 minute presentations each followed by 5 minute of discussion)

ToxCast Update: Russell Thomas, US Environmental Protection Agency

EDSP21 Update: David Dix, US Environmental Protection Agency

Tox21 Update: Richard Paules, US National Toxicology Program

Hamner TT21C Update: Melvin Andersen, Hamner Institutes

NICEATM Update: Warren Casey, NICEATM

SEURAT/EU Tox-Risk Update: Michael Schwarz, University of Tuebingen

CAAT’s Read-Across Initiative and Human Toxome-Related Activity Update: Thomas Hartung, Johns Hopkins

Human Toxicology Project Consortium Update: Catherine Willett, HTPC

Evidence-Based Toxicology Update: Martin Stephens, Johns Hopkins

3:15 PM—Open Microphone for Additional Presentations and Discussion

4:00 PM—Adjourn

  • Kate Willett will also present a poster in the Regulation and Policy session, Wednesday, March 16, 1:15 PM to 4:45 PM: “Regulatory Acceptance of Non-standard Toxicological Methods through Increased use of Integrated Approaches to Testing and Assessment (IATA)” (Abstract #3003/Poster #P143).

Corporate members and partners of HTPC will be presenting at SOT next week, as well.  Scientists from each of the member corporations are coauthors on the following posters:

alternative toxicity testing AOPs CAAT computational toxicology Dow EPA ExxonMobil HTPC members in the news HTPC partners L'Oreal P&G regulatory toxicology Tox21 ToxCast Unilever

Educational Infographic produced by the Human Toxicology Project Consortium

THE FUTURE OF TOXICITY TESTINGHTP_infographic_FINAL_revised

A new infographic produced by the Human Toxicology Project Consortium shows in three sections how the future of toxicity testing promises a steady reduction in testing costs, increases in human relevance and confidence in safety assessments, and the eventual elimination of animal tests.

The first section provides a snapshot comparison of the current and future costs, efficiency and efficacy of toxicity testing, while the mid portion uses pesticide testing as a specific example of now, vs near-future, vs the optimal approach that, given the focus and resources necessary, will be envisioned within the decade.

The near-future and optimal approaches rely increasingly on our understanding of biology and using it to build a predictive systems biology platform that is comprised of an interrelated network of biological pathways. This platform is used to design and interpret tests that provide much more efficient and effective characterization of chemical activity that can be used to predict safe use of chemicals.

Finally, the results of this progression are captured in the summary graphic at the end – decreasing costs, animal use and time while human relevance and our confidence in safety decisions continue to improve.

As explained on our Project page, the Human Toxicology Project Consortium works on three areas critical for the successful, international implementation of a pathways-based approach to chemical safety testing: advancing the science, communicating the purpose and goals of pathway-based toxicology, and lobbying for funding and policy changes that will support pathway-based approaches in the US and around the world.

To advance our communication and education efforts, HTPC member organizations worked together to create this infographic, to quickly and effectively illustrate the differences between traditional animal-based toxicity testing and pathway-based testing in terms of predictive power, cost, and testing capacity.

Details on the numbers used in this comparison are available here (PDF).

alternative toxicity testing AOPs computational toxicology databases drug discovery EPA HTPC members in the news non-animal tests non-predictive animal models pathway-based approaches regulatory toxicology ToxCast toxicity testing alternatives

A new paper applies pathway biology to disease research and drug discovery

“Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research,” a new paper by a team of international experts including authors from Human Toxicology Project Consortium partners Humane Society International, The Humane Society of the United States, and Unilever, calls for a systems-biology approach to biomedical research and drug discovery. The approach borrows insights from toxicology, where adverse outcome pathways (AOPs) – a framework for documenting the physiological path between chemical exposure and “adverse outcomes” such as illness, injury, or environmental harm – are being used to integrate data from a variety of new scientific technologies. The authors propose that this same framework can be expanded to disease research, and can greatly improve our ability to identify effective drugs and therapeutics.

“…[M]any human illnesses such as cancers, diabetes, immune system and neurodegenerative disorders, and respiratory and cardiovascular diseases are caused by a complicated interplay between multiple genetic and environmental factors,” the authors write. Technology developments over the last two decades have made it possible to measure how genes determine our susceptibility to diseases, as well as how genes, proteins, cells, and tissues react to various environmental exposures. Application of such developments to drug discovery “require(s) a new research paradigm to unlock their full potential.” Just as AOPs integrate these new types of information to help reveal toxicity mechanisms and protect people and the environment from potential effects of chemical exposure, disease pathways can be used to understand risk and disease mechanisms, leading to more effective cures. According to the authors, “The disease AOP approach would better exploit advanced experimental and computational platforms for knowledge discovery, since the emergence of AOP networks will identify knowledge gaps and steer investigations accordingly.”

Progress in disease research and drug discovery has been slow, the authors say, because of continued reliance on inappropriate and unproductive animal models. The AOP framework encourages the use of emerging human-specific cell- and tissue-based models – such as 3D tissue constructs and organs-on-chips – combined with increasingly advanced computational models. The powerful combination can accelerate our understanding of disease, while reducing the use of animals.

The paper was published in the open access journal, Environmental Health Perspectives: http://ehp.niehs.nih.gov/wp-content/uploads/123/11/ehp.1510345.alt.pdf

3D cell & tissue culture alternative toxicity testing AOPs drug discovery HTPC members in the news pathway-based approaches

China developing a roadmap to twenty-first century toxicity testing

At a special symposium last month in Xi’an, China, participants began to map China’s regulatory steps toward twenty-first century toxicology and away from animal testing.

The symposium, “TT21C/AOP China Roadmap,” was part of a conference on alternatives to animal tests in toxicology that was hosted by the Chinese Society of Toxicology’s Committee on Toxicological Alternatives and Translational Toxicology and the Chinese Environment Mutagen Society’s Committee on Toxicity Testing and Alternative Methods, and co-sponsored by the Humane Society International (HSI), Unilever, L’Oreal, and Shell. The symposium was convened “to address the need to increase Chinese regulatory uptake of currently available alternatives and the AOP paradigm.” Human Toxicology Project Consortium coordinator Dr. Catherine Willett was an invited speaker (a PDF of her presentation, “Use of Adverse Outcome Pathways (AOPs) to Reduce Uncertainty and Animal Use in Chemical Hazard and Risk Assessment,” is available).

During the symposium, a working team comprised of members from the host societies and representatives from Unilever, L’Oreal, HSI, and others was established to begin working on the twenty-first century toxicology “roadmap.” Asked about the team’s next steps in a Chemical Watch article (subscription required) about the symposium, Dr. Carl Westmoreland (Director of Science and Technology at Unilever’s Safety and Environmental Assurance Centre, and a member of the working team) said the host committees will prepare a summary of the proceedings and circulate it to participants for review.

alternative toxicity testing AOPs HSI HTPC members in the news L'Oreal Meetings & Events pathway-based approaches Unilever
Picture of video reel, by Coyau / Wikimedia Commons / CC-BY-SA-3.0

AOPs 201: Presentation videos now available

Building on progress since a successful “AOPs 101” seminars at the Society of Toxicology meeting in 2014, and at the World Congress on Alternatives and Animal Use in the Life Sciences in Prague (2014), the Human Toxicology Project Consortium (HTPC) and the Physicians Committee for Responsible Medicine PCRM offered a more advanced seminar at the Society of Toxicology 2015 meeting in San Diego.  The new seminar reviewed the tools and guidance currently available to help users develop and record AOPs, and presented case studies of AOPs in various stages of development to demonstrate the major developmental steps.

Videos of the seminar presentations are available below.  The presentations included:

AOPs: Overview of AOP Development and Introduction to Regulatory Use

  • Catherine Willett, HTPC

The AOP-Knowledgebase, with demos of the AOP Wiki, Effectopedia, and AOP Explorer (+ questions)

  • Ed Perkins, US Army Engineer Research and Development Center
  • Steven Edwards, US EPA
  • Hristo Aladjov, OECD

Aromatase inhibition leading to reproductive dysfunction in fish: A quantitative AOP case study

  • WanYun Cheng, EPA

AOP for Sensitisation of the Respiratory Tract: Current status and regulatory applications

  • Kristie Sullivan, PCRM

AOP Assessment According to OECD Handbook Criteria

  • Bette Meek, University of Ottawa

Note: these videos are also accessible through our AOPs 201 page.

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