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.

AOP tutorials AOPs
mtg room crop

Report on the SOT Satellite Meeting, “Updates on Activities Related to 21st Century Toxicology and Evidence-based Toxicology”

(Reprinted from the April AltTox Digest; used with permission.)

At the start of this year’s SOT satellite meeting, “Updates on Activities Related to 21st Century Toxicology and Evidence-based Toxicology” (co-sponsored by the Center for Alternatives to Animal Testing [CAAT], the Human Toxicology Project Consortium [HTPC] and the Evidence-based Toxicology Collaboration [EBTC]), co-moderator Thomas Hartung noted that the annual gathering began in 2009 with 12 people in attendance.  This year, at least 80 people attended – an impressive crowd for a meeting that takes place in the final hours of the week-long Society of Toxicology convention. The annual meeting features updates on US and EU programs and projects dedicated to advancing the toxicity-testing paradigm outlined in the NRC’s 2007 report, Toxicity Testing in the 21st Century: A Vision and a Strategy.

Richard Paules (US National Toxicology Program) started the presentations with a report on progress in the interagency Tox21 program. The program has moved into Phase III, during which they will be increasing the use of computer models for in vitro to in vivo extrapolation, adding new cell lines, expanding the pathway coverage and human relevance of assays, and developing a high-throughput (HT) transcriptomics platform.

Rusty Thomas (US Environmental Protection Agency) then described a number of initiatives underway in the ToxCast program, including research to develop the metabolic competence of existing assays, developing new assays for priority targets such as the thyroid, and exploring the use of organotypic cell cultures. ToxCast is also expanding its read-across program (and recently hired AltTox Editorial Board member Grace Patlewicz to spearhead that effort).

David Dix (US Environmental Protection Agency) gave an overview of the progress in the EPA’s Endocrine Disruptor Screening Program (EDSP), noting that improved technologies are greatly accelerating the project. The agency is concentrating on building user confidence in its screening battery and expanding the use of computational modeling. (Read an introduction to the EDSP in this two-part In the Spotlight article.)

Melvin Andersen (Hamner Institutes), a co-author of the NRC’s 2007 report, noted that considerable technical and scientific progress has been accomplished in the 8 years since publication of the NRC’s recommendations. Several key pathways have been well-described, and others are under construction. The new challenge is to determine how to communicate this progress to the public, and build their confidence in these methods.

Mark Cronin (Liverpool John Moores University) then provided an overview and update on the six components of the EU’s SEURAT-1 program. (Read more about the SEURAT-1 program in this New Perspective article.) A number of useful tools are coming out of this project, but the key outputs are proof-of-concept case studies. Level 1 studies are designed to demonstrate methods for consolidating existing knowledge to describe key adverse outcome pathways (AOPs). Level 2 studies demonstrate the integration of in vitro and in silico tools to generate predictive models. Level 3 studies, to be finalized later this year, will demonstrate how these models and knowledge bases can be used in quantitative and read-across-based risk assessment and decision-making.

Thomas Hartung reported on the activities of CAAT. Among many initiatives, CAAT is developing a read-across program that aims to facilitate 2018 REACH registrations. CAAT has also been coordinating a series of workshops in Europe and the US to advance “green toxicology” – using in silico tools to design safer chemicals. Filling in for scheduled presenter Marty Stephens, Hartung also described the work of the EBTC, which has been developing and promoting the methods and uses of systematic review in toxicology. Hartung noted that evidence-based toxicology stands to advance twenty-first century toxicology in several ways, including providing a means of assessing the quality of legacy data and new assays, providing guidance on integrating data sources, and ultimately using this information to facilitate validation procedures.

Catherine Willett updated the group on HTPC activities. Willett explained that the HTPC focuses its efforts on three areas: contributing to the advance of relevant science by sponsoring workshops and seminars, lobbying in the US and EU to increase funding for key government initiatives, and developing communication strategies to encourage regulatory and public acceptance of the NRC’s testing strategy. In the last year, the group has especially concentrated on this third area, developing an informative graphic and a series of videos that will be posted on the group’s website later this year. She noted that the HTPC also co-sponsored a seminar at SOT this year – “AOPs 201,” which covered the development and use of AOPs for regulatory purposes. Videos from the seminar will be shared on the group’s website.

The meeting closed with its traditional “open mic” segment – inviting short presentations or discussion questions from those in attendance. The update meeting will convene again at the end of next year’s SOT convention in New Orleans.

(Registered participants of the meeting will be able to access presentation slides on the EBTC website.)

alternative toxicity testing AOPs computational toxicology HTPC partners Meetings & Events Tox21 ToxCast
SatelliteRoom

HTPC co-sponsoring two events at the Society of Toxicology annual meeting in San Diego

The Human Toxicology Project Consortium will once again co-sponsor two ancillary events at the Society of Toxicology’s annual meeting in San Diego in March.

Along with the Physicians Committee for Responsible Medicine, we’re excited to expand the popular AOPs 101 series with a new workshop: “AOPs 201”: A Seminar on Development, Recording, and Use of Adverse Outcome Pathways.  This event will take place Monday, March 23, from 5:00 PM–7:30 PM (local time) at the San Diego Marriott Marquis & Marina in Marina Ballroom F.

Then on March 26, we’ll join HTPC partner Center for Alternatives to Animal Testing and the Human Toxome Project in co-sponsoring the annual satellite meeting, Updates on Activities Related to 21st Century Toxicology and Evidence-based Toxicology: Invited Presentations and Open Microphone.  This event will be held in the Hillcrest Room of the Manchester Grand Hyatt in San Diego, from 12:30 to 4:00 PM (local time).  Invited speakers and topics include:

  • Richard Paules (US National Toxicology Program) – Tox21 Update
  • Russell Thomas (US Environmental Protection Agency) – ToxCast Update
  • David Dix (US Environmental Protection Agency) – EDSP21 Update
  • Melvin Andersen (Hamner Institutes) – Hamner TT21C Update
  • Mark Cronin (Liverpool John Moores University) – SEURAT Update
  • Thomas Hartung (Johns Hopkins) – CAAT’s Read-across Initiative and Human Toxome-related Activity Update
  • Catherine Willett (HTPC) – Human Toxicology Project Consortium Update
  • Martin Stephens (Johns Hopkins) – Evidence-based Toxicology Update

For those planning to attend SOT 2015, more information about this satellite meeting is available here (the event is free; box lunches will be provided to pre-registrants).

AOPs Meetings & Events
iStock_000039820244_Large

Advancing Species Extrapolation: EPA’s “Sequence Alignment to Predict Across Species Susceptibility” | Science

…SeqAPASS provides us with a fast, efficient screening tool. Using it, we can begin to extrapolate toxicity information from a few model organisms (like mice, rats, zebrafish, etc.) to thousands of other non-target species to evaluate potential chemical susceptibility.

SeqAPASS provides an example of how EPA Chemical Safety for Sustainability researchers are leading the effort to usher in a new generation of toxicology practices that aspire to reduce the number of animals used, decrease costs, and increase the efficiency of chemical toxicity testing. The 21st century chemical toxicity testing strategy incorporates these ideals and has given rise to adverse outcome pathway (AOP) development and rapid, high-throughput chemical screening programs such as EPA’s ToxCast program.

Read more on the EPA’s science blog: Advancing Species Extrapolation: EPA’s “Sequence Alignment to Predict Across Species Susceptibility” | Science.

alternative toxicity testing AOPs computational toxicology databases EPA ToxCast
Male thyroid anatomy

Paper encouraging non-animal approaches to metabolism wins award

Among the awards bestowed at the 9th World Congress for Alternatives and Animal Use in the Life Sciences in August, a paper co-authored by consortium director Catherine Willett was named the journal ALTEX’s “Best ALTEX article of 2013.”

In vitro Metabolism and Bioavailability Tests for Endocrine Active Substances: What is Needed Next for Regulatory Purposes?” by Miriam N. Jacobs, Susan C. Laws, Kate Willett, Pat Schmieder, Jenny Odum, and Toine F. Bovee, revisits and expands on recommendations put forth in a 2008 OECD review paper that argued for the assessment of human metabolism in in vitro assays used to screen endocrine-active substances.  Although that earlier paper showed that many of the necessary screening tools were already available, little progress has been made by the European, US, or Japanese validation agencies toward validating such methods for use in a regulatory context.  In the ALTEX paper, Jacobs et al. outline a series of projects designed to accelerate validation, continue to expand the number of available metabolism-enhanced screening assays, and improve and expand predictive tools.

 

alternative toxicity testing AOPs OECD Publications
AOP-KB

OECD launches the AOP Knowledge Base

The OECD, along with the US Environmental Protection Agency and the European Commission Joint Research Centre, today announced the public release of the Adverse Outcome Pathway Knowledge Base.  The web-based platform is designed to consolidate all existing information on the mechanisms and pathways through which chemicals can cause or contribute to adverse effects.  The first available module is the AOP Wiki, an online, interactive encyclopedia for AOP development.  From the OECD press release:

“All stakeholders from academia, governmental agencies and the chemical industry are invited to use the wiki either as a source of information, or as active contributors posting comments and content. This expert contribution from third-parties is strongly encouraged since it is through such “crowd sourcing” that the AOP KB will ultimately evolve.”

At the annual meeting of the Society of Toxicology in Phoenix earlier this year, HTPC co-sponsored several AOP Knowledge Base “Stakeholder Input Sessions” designed to gather ideas from potential users about the features and information they would find most essential in these tools.  That process is ongoing.  As noted in the OECD press release,

“By opting for this early public release, the OECD aims to familiarise interested parties with AOP concepts and terminology through interaction with the AOP Wiki, with the hope of engaging as many potential AOP developers and contributors as possible.”

The AOP Knowledge Base is a key component of the comprehensive AOP Development Program launched by the OECD in 2012.

AOPs EPA OECD
Nicole Kleinstreuer (ILS, Inc./NICEATM)

Another successful “AOPs 101” session

Anne Gourlemon (OECD)

Anne Gourlemon (OECD)

On Sunday, August 24 – just ahead of the 9th World Congress on Alternatives and Animal Use in the Life Sciences (“WC9″) in Prague – the HTPC and Physicians Committee for Responsible Medicine (PCRM) co-sponsored an “AOPs 101” session.  Like the sessions offered at SOT earlier this year, this one was designed to introduce the Adverse Outcome Pathway concept to scientists who want to learn more about it, including how to apply it in their own work.

The session opened with an overview and introduction by Catherine Willett (HTPC).  Anne Gourmelon presented on the OECD’s AOP program.  Kristie Sullivan (PCRM) gave an introduction to the AOP Wiki, and Hristo Aladjov (OECD) introduced Effectopedia.  These overview talks were followed by two case study presentations: Joanna Jaworska (Procter & Gamble) described the use of AOPs in a Bayesian network ITS framework to assess skin sensitization, and Nicole Kleinstreuer (ILS, Inc./NICEATM) described the construction of AOPs for developmental toxicities.  The talks generated excellent follow-up questions and discussion.

Nicole Kleinstreuer (ILS, Inc./NICEATM)

Nicole Kleinstreuer (ILS, Inc./NICEATM)

Kristie Sullivan (PCRM)

Kristie Sullivan (PCRM)

9th World Congress on Alternatives AOPs Meetings & Events