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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
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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).

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CAAT's stem cell-derived "mini-brain"/image by Thomas Hartung (used with permission)

Researchers at HTPC partner organization CAAT create stem-cell derived mini-brains

CAAT's stem cell-derived "mini-brain"/image by Thomas Hartung (used with permission)

CAAT’s stem cell-derived “mini-brain”/image by Thomas Hartung (used with permission)


Researchers at Johns Hopkins’ Center for Alternatives to Animal Testing (CAAT) have developed a process to create “mini-brains” derived from stem cells reprogrammed from human skin cells. The resulting structures exhibit a number of cell types and cell functions of the human brain, and can be produced economically and in sufficient numbers to be especially useful for screening chemicals and drug candidates. The mini-brains will also be used to study Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and autism.

From CAAT’s press release:

“[Principal investigator] Hartung and his colleagues created the brains using what are known as induced pluripotent stem cells (iPSCs). These are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state and then are stimulated to grow into brain cells. Cells from the skin of several healthy adults were used to create the mini-brains, but Hartung says that cells from people with certain genetic traits or certain diseases can be used to create brains to study various types of pharmaceuticals. He says the brains can be used to study Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and even autism. Projects to study viral infections, trauma and stroke have been started.

Hartung’s mini-brains are very small—at 350 micrometers in diameter, or about the size of the eye of a housefly, they are just visible to the human eye—and hundreds to thousands of exact copies can be produced in each batch. One hundred of them can grow easily in the same petri dish in the lab. After cultivating the mini-brains for about two months, the brains developed four types of neurons and two types of support cells: astrocytes and oligodendrocytes, the latter of which go on to create myelin, which insulates the neuron’s axons and allows them to communicate faster.

The researchers could watch the myelin developing and could see it begin to sheath the axons. The brains even showed spontaneous electrophysiological activity, which could be recorded with electrodes, similar to an electroencephalogram, also known as EEG. To test them, the researchers placed a mini-brain on an array of electrodes and listened to the spontaneous electrical communication of the neurons as test drugs were added.

“We don’t have the first brain model nor are we claiming to have the best one,” says Hartung, who also directs the School’s Center for Alternatives to Animal Testing.

“But this is the most standardized one. And when testing drugs, it is imperative that the cells being studied are as similar as possible to ensure the most comparable and accurate results.”

Hartung elaborated on this point to Gizmodo: “There are a handful of such models described over the last two years,” he said. “They show more fancy brain structures, but each and every one looks different, often with cells in the middle dying because of lack of oxygen as they have no blood vessels. We produce hundreds of identical mini-brains, every week. This is critical for testing and comparing substances. They have exactly the same size below a critical diameter.”

Learn more in the video embedded here.

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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

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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.

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HTPC member Unilever partners with the EPA to develop non-animal approaches to safety testing

Human Toxicology Project Consortium member Unilever announced Tuesday that it will be collaborating with the US Environmental Protection Agency on a project that will improve and advance human-relevant chemical safety assessment while phasing out the use of animals.

The project will create case studies around chemicals of mutual interest, using existing data from the Toxcast and Tox21 programs combined with Unilever’s data and methods for estimating consumer exposures, and testing new high-throughput screening methods that account for metabolism and more completely assess human biological pathways.

Quoted in the joint press release, Russell Thomas, Director of EPA’s National Center for Computational Toxicology, said that if the project is successful, “research from this collaboration will result in better ways to evaluate the potential human health effects of new ingredients and chemicals we currently know little about. …These methods could be used by both industry and governmental agencies to reduce the costs associated with safety testing and accelerate the pace of chemical risk assessment.” And Julia Fentem, Vice President of Unilever’s Safety and Environmental Assurance Centre, said, “This research collaboration is strategically very important for Unilever’s long-held ambition to eliminate the need for any animal testing while also continuing to ensure the safety of consumers and our environment. If we had robust scientific tools to accurately and rapidly predict exposures to chemicals at the cellular and molecular levels within the human body, this would be a huge step forward in being able to conduct safety risk assessments without using animal data.”

alternative toxicity testing EPA HTPC members in the news non-animal tests pathway-based approaches Tox21 ToxCast Unilever
organovo bioprinter

“L’Oreal at work on bioprinted skin for cosmetics testing”

5/21/2015 Update: News of the Organovo/L’Oreal partnership, posted here in December, seems to be captivating the wider press, now.  See especially these stories in the Washington Post, Bloomberg Business, and Wired UK.

In the span of just a few years, 3D-bioprinting (3D-printing of biological cell and organ components) has moved from the realm of science fiction to scientific reality – a technology capable of printing viable skin, liver, and other organ tissues that can be used for more human-relevant drug testing, disease-modeling, and even transplantation research.

This article from CosmeticsDesign.com highlights the collaboration between 3D-bioprinting pioneer Organovo and HTPC corporate partner L’Oreal, who are working together to create a bioprinted skin tissue that can be used in cosmetics testing:

L’Oreal at work on bioprinted skin for cosmetics testing.

(For more on Organovo’s bioprinting technology, watch this video.)

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