Sleepless in Seattle: An update from the World Congress on Alternatives and Animal Use in the Life Sciences

Our experts will be working round-the-clock in Seattle this week at the World Congress on Alternatives and Animal Use in the Life Sciences! Over the next several days, staff from The Humane Society of the United States, Humane Society International & The Humane Society Legislative Fund will be at the vanguard of the discussion at this global event that brings together the world’s foremost experts on animal testing alternatives & animal welfare from industry, government, non-profits & academia.

Are you in Seattle, too? Please visit us at our booth (#309) and plan to attend the following events! Somewhere else in the world? Check out what we’re up to below and view the World Congress program.

SUNDAY, AUGUST 20

• 10:00 a.m. – noon
“Introduction to Adverse Outcome Pathways and the AOP Wiki” Satellite Meeting
Sheraton Seattle, Aspen Room
10:00 a.m. Introduction to the OECD AOP Programme and Online Training course – Kate Willett, Human Toxicology Project Council
10:40 a.m. Building AOPs for Neurotoxicity: Perspective from an Academic – Ellen Fritsche, IUF – Leibniz Research Institute for Environmental Medicine
11:20 a.m. Demonstration and Hands-On Activity with AOP Wiki – Kristie Sullivan, Physicians Committee for Responsibility MedicineSponsors: Human Toxicology Project Consortium and the Physicians Committee for Responsible Medicine

MONDAY, AUGUST 21

• 12:15 p.m. – 1:15 p.m.
“Tracking the successful implementation of Tox21 principles.”
Room 6ABC, Board number A43
Poster presenter Vicki Katrinak looks at how the chemical safety testing landscape has changed over the past ten years, as toxicologists embrace new, non-animal testing strategies.

• 12:15 p.m. – 1:15 p.m.
“Legislative process toward animal testing bans for cosmetics in Brazil.”
Room 6ABC, Board number A44
Poster presenter Antoniana Ottoni discusses how the Brazilian authorities aim to implement validated alternative, non-animal tests for commonly used toxicological endpoints and reviews plans to ensure the regulations are updated before the deadline of 2019.

• 2:00 p.m.
“Implications of the Recent 2016 Amendment of the Toxic Substances Control Act (TSCA) on the Development and Implementation of Non-Animal Methods.”
Session II-2: Government Driven Legislation – EDSP/TSCA; 1:15 p.m. – 2:45 p.m.; Rooms 613-614
Speaker Catherine Willett will explain how animal testing could actually increase under the new chemical safety act, and describe how co-ordinated efforts are needed to exploit non-vertebrate models and other evaluation tools to prevent this.

TUESDAY, AUGUST 22

• 10:30 a.m.
“Challenges in implementing the Frank R. Lautenberg Chemical Safety for the 21st Century Act: A perspective covering stakeholders, the U.S. Congress and the current Administration.”
Session IX-4: Global Regulatory Updates; 10:00 a.m. – noon; Room 607
Speaker: Sara Amundson

• 12:15 p.m. – 1:15 p.m.
“Modeling the human airways: from physiology to pathology.”
Room 6ABC, Board number A65
Poster presenter Lindsay Marshall shows how laboratory models using human cells can be used to look at the function of healthy airways and demonstrates that the models can be adapted to enable the study of airways disease, such as cystic fibrosis.

• 12:15 p.m. – 1:15 p.m.
“iPSC and 3D tissue technologies powerful alternatives to animal models for brain disease research”
Room 6ABC, Board number A77
Poster presenter Marcia Triunfol reports on an exciting, HSI-sponsored workshop held in Brazil earlier this year. Brazilian and international scientists discussed the potential for 21st century technologies to replace animals in brain research.

WEDNESDAY, AUGUST 23

• 12:15 p.m. – 1:00 p.m.
“A ‘bottom-up’ approach to accelerate new opportunities in alternatives and Adverse Outcome Pathway (AOP) practice in China”
Room 6ABC, Board number C81
Poster presenter Tina Qu reports on the progress made in promoting non-animal technologies in China, including the recent roll-out of an AOP-training program.

• 10:45 a.m.
“Towards a 21st-century roadmap for biomedical research and drug discovery”
Session IX-8: Global Efforts Moving Towards Replacement of Animals;
10:00 a.m. – noon; Rooms 619-620
Speaker Troy Seidle describes the application of pathways-based approaches to understand chemical safety and details how a series of workshops sponsored by The Humane Society of the United States and Humane Society International have introduced this concept to other stakeholders – describing the main recommendations from these events.

THURSDAY, AUGUST 24

• 10:48 a.m.
“The Human Toxicology Project Consortium: a private-public partnership to promote development and acceptance of pathway-based science”
Session IX-6: 3Rs Communication and Advocacy; 10:00 a.m. – noon; Rooms 619-620
Speaker Catherine Willett will describe the work of the Human Toxicology Project Consortium (HTPC), which aims to advance a biological pathway-based approach to toxicology. She will explain how HTPC intends to achieve this through scientific activities, communication, and advocating for financial and legislative support.

• 11:45 a.m.
“Deletion of scientifically redundant animal test requirements in the agrochemical sector: the case of the 1-year dog study”
Session IV-1: Predictive Safety Approaches Role in the Design of Inherently Safer Chemicals; 10:00 a.m. – noon; Rooms 615-616
Speaker Marco Corvaro will explain how the ongoing global effort to end a test that has been proven redundant illustrates how challenging it can be to enact regulatory change. He will also discuss strategies to improve the use of modern approaches to testing and risk assessment.

• 11:46 a.m.
“A campaign to end invasive chimpanzee research and retire all chimpanzees to sanctuaries: successful strategies and lessons learned”
Session IX-6: 3Rs Communication and Advocacy; 10:00 a.m. – noon; Rooms 619-620
Speaker Kathleen Conlee will take us from 2006, when The Humane Society of the United States launched their campaign to end the use of chimpanzees in invasive research, to today where numbers of chimps in labs have dropped and research chimps are finally being retired to sanctuaries.

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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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Human Toxicology Project Consortium coordinator participates in a TSCA science briefing on Capital Hill

At a recent Capital Hill science briefing organized by the American Chemical Society (ACS) and the American Chemistry Council (ACC), Human Toxicology Project Consortium coordinator Kate Willett joined toxicologists from industry and the EPA to discuss how reforms to the Toxic Substances Control Act (TSCA) can capitalize on scientific advances in non-animal test methods.  Participants explained how technologies such as high-throughput screening, organs-on-chips, and computational modeling will improve the relevance and efficiency of safety assessments, and produce crucial information more quickly. The Royal Society of Chemisty’s Chemistry World covered the briefing.

The experts gathered at the briefing agreed that tremendous advances had been made since the 1970s in understanding how chemicals can interact with biological systems – at the molecular, cellular and organ level. For example, high throughput screening now enables thousands of chemicals to be evaluated in a matter of hours or days….

Kate Willett, a toxicologist at the Humane Society of the US, noted that the critical goal of [TSCA] is to protect human health and the environment. This means a system is needed that can quickly identify potential problems and address them in the most time- and cost-effective way possible.

Willett stressed that any new TSCA reform measure must allow for “the continuing evolution of this science.” Therefore, she said the final updated law should require that all alternative approaches are used before moving to animal testing. “Reducing reliance on animal testing allows more chemicals to be more thoroughly assessed in the most efficient way possible – a win for environmental protection and the industry, and also for the animals that are used in this testing.”

The House and Senate have both passed TSCA reform bills (H.R. 2576 and S. 697) and now must reconcile differences between the two versions.

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artistic rendering of kidney xray

A high-speed image-based system for predicting kidney toxicity

Scientists from Singapore’s A*STAR Bioinformatics Institute and the Institute of Bioengineering and Nanotechnology have developed a computerized cell imaging system that can predict with up to 90% accuracy whether a chemical will be toxic to human kidney cells. The system is more accurate than animal tests, and faster than existing in vitro methods for predicting kidney toxicity.

To create the system, the investigators screened over 2 million individual cells that had been treated with more than 40 different compounds – including industrial chemicals, agricultural chemicals, and various pharmaceuticals. They took microscopic images of the cells following each exposure and examined the images for signs of structural changes or damage to the cells. Those cells treated with compounds known to cause kidney toxicity showed a pattern of changes the team used to construct a “toxicity profile.” By training their image analysis software to look for these features in other cell images, they developed a highly accurate, high-speed, automated screening system.

Last summer the team announced a stem cell method for producing a reliable supply of human kidney cells for in vitro screening. However, they noted in the current paper that certain steps in the earlier procedure are difficult to automate.  The new image-based screening system can be completely automated, allowing investigators to screen a much larger number of chemicals in a shorter period of time.

Original article: Su et al. (2015) High-Throughput Imaging-Based Nephrotoxicity Prediction for Xenobiotics with Diverse Chemical Structures. [Open access]

high-speed imaging non-animal tests stem cells
artistic rendering of kidney xray

A non-animal method for predicting kidney toxicity

Scientists at Singapore’s Institute of Bioengineering and Nanotechnology have created a non-animal drug screening method that uses stem cell-derived human kidney cells to predict the toxicity of drugs and other chemicals. The method improves on the reliability and availability of earlier stem cell models, promises to reduce the costs and time it takes to test and develop new drugs, and could eventually eliminate certain animal tests.

iStock_kidney-larger-cropBecause of their role in filtering blood, the kidneys are especially vulnerable to any toxic effects of drugs and other substances that pass through them, but predicting the renal toxicity of such substances has been difficult. As the authors write in their article in Scientific Reports, “Typically, compound nephrotoxicity is only detected during late stages of drug development, which is associated with high costs for the pharmaceutical industry. Animal models have limited predictivity and the development of renal in vitro models with high predictivity has been challenging.”

Using primary human kidney cells in toxicity tests is difficult, as well, due to high variability between donors, and difficulties keeping the cells fully functional during tests. For these reasons, generating a reliable supply of kidney cells from stem cells is preferable. Previous human kidney cell models (including one published by the authors) were produced from human embryonic stems cells (hESCs), which are difficult to access and which raise ethical concerns. This new method instead uses induced pluripotent stem cells (iPSCs) created from more readily available cells, such as human skin cells. iPSCs are genetically “reprogrammed” to an early developmental state, from which they can be coaxed into other kinds of cells. The team’s method produces usable kidney cells within 8 days – much faster than previous stem cell models, as well.

To learn more about using stem cells in toxicity testing, read the “primer” on AltTox.org.

alternative toxicity testing non-animal tests stem cells

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