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Updates from the Center for Alternatives to Animal Testing (CAAT)
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April 27, 2019

News and Updates from CAAT

   Contents:


Thomas Hartung Appointed Editor of Frontiers in Artificial Intelligence

Big Data and Artificial Intelligence (AI) are reshaping our world, revolutionizing the way we work and live. Last year, Frontiers launched Frontiers in Artificial Intelligence. The journal publishes a broad range of topics in AI by bridging gaps between disciplines. Frontiers in Artificial Intelligence will be led by Thomas Hartung, Director of CAAT and professor of toxicology at he Johns Hopkins Bloomberg School of Public Health. 

“AI is about making sense of Big Data, which is relevant in all sciences," Hartung explains. "It complements hypothesis-driven research by moving Data Mining from a fishing expedition to an intelligent query of assembled facts.”

“Scientists on the editorial board supporting Frontiers in Artificial Intelligence are foremost experts in their disciplines," Hartung continues. "AI is such a cross-cutting technology—it is fascinating how this disruptive and enabling technology fertilizes so many disciplines. Researchers contributing to this area demonstrate true courage. They cross those boundaries to collaborate with each other and find answers to common questions from sharing data and algorithms, to quality assurance, to ethics.”

Frontiers in Artificial Intelligence (Journal)
 





CAAT and Hopkins Researchers ID Neurotransmitter that Helps Cancers Progress

Using human cancer cells, tumor and blood samples from cancer patients, researchers at Johns Hopkins Medicine have uncovered the role of a neurotransmitter in the spread of aggressive cancers. Neurotransmitters are chemical "messengers" that transmit impulses from neurons to other target cells.

The work, described in the April 9 issue of the journal Cell Reports, found that this neurotransmitter, called N-acetyl-aspartyl-glutamate (NAAG) NAAG is more abundant in cancers with a tendency to grow and spread rapidly—or so-called higher grade cancers—than in lower grade tumors, making it a potential marker for tumor progression or regression during cancer therapy, the researchers say. The experiments also demonstrated that NAAG is a source of glutamate, a chemical that cancer cells use as building blocks to survive, in tumors that express an enzyme called glutamate carboxypeptidase II (GCPII). The group also discovered that stopping the GCPII from being active by using a drug called 2-PMPA to treat human ovarian tumors implanted in ovaries of mice, reduced tumor weights and glutamate concentrations. They noted that targeting both GCPII and glutaminase, the enzyme that converts glutamine to glutamate, resulted in a more substantial tumor reduction in patient-derived pancreatic cancer tumors implanted in pancreas of mice, since it attacked the production of glutamate from both glutamine and from NAAG.

CAAT's Thomas Hartung and Andre Kleensang co-authored the paper. 

Full Press Release

Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer (Cell Reports)
 


 

New Publication: Nonanimal Models for Acute Toxicity Evaluations: Applying Data-Driven Profiling and Read-Across

The use of animals to test the toxicity of chemicals may one day become outdated thanks to a low-cost, high-speed algorithm developed by researchers at Johns Hopkins, Rutgers, and other universities.

Toxicity testing—determining the amount of exposure to a chemical that is unsafe for humans—is vital to the safety of millions of workers in various industries. But of the 85,000 compounds used in consumer products, the majority have not been comprehensively tested for safety. Animal testing, in addition to its ethical concerns, can be too costly and time consuming to meet this need, according to the study published in Environmental Health Perspectives.

"There is an urgent, worldwide need for an accurate, cost-effective and rapid way to test the toxicity of chemicals, in order to ensure the safety of the people who work with them and of the environments in which they are used," Daniel Russo, lead researchers and a doctoral candidate at the Rutgers University-Camden Center for Computational and Integrative Biology, said. "Animal testing alone cannot meet this need."

Previous efforts to solve this problem used computers to compare untested chemicals with structurally similar compounds whose toxicity is already known. But those methods were unable to assess structurally unique chemicals—and were confounded by the fact that some structurally similar chemicals have very different levels of toxicity.

The Rutgers-led group overcame these challenges by developing a first-of-its-kind algorithm that automatically extracts data from PubChem, a National Institutes of Health database of information on millions of chemicals. The algorithm compares chemical fragments from tested compounds with those of untested compounds, and uses multiple mathematical methods to evaluate their similarities and differences in order to predict an untested chemical's toxicity.

Thomas Hartung co-authored the paper, which appears in the April issue of Environmental Health Perspectives.

https://doi.org/10.1289/EHP3614

 



DEADLINE ALERT!
CAAT Grants: Call for Preproposals

Deadline: May 5, 2019

The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) is soliciting projects that focus on the implementation of the NAS Report: Toxicity Testing in the 21st Century: A Vision and a Strategy in the following areas:

  • Proposals Relating to Toxicology: Maximum grant amount is $40,000. The objective should be to significantly reduce or replace laboratory animals. Examples of acceptable projects could include: providing mechanistic understanding of in vitro responses to toxicants in human cells, development of AOPs, or conducting systematic reviews. Consideration should be given to the translation of this new method to evaluate/predict health outcomes.

CAAT VISION

  • To be the leading force in the development and use of reduction, refinement, and replacement alternatives* in research, testing, and education to protect and enhance the health of the public.

CAAT MISSION

  • Promote and support research in the development of in vitro and other alternative techniques.
  • Serve as a forum to foster discussion among diverse groups leading to creative approaches to facilitate acceptance and implementation of alternatives.
  • Provide reliable information on the science, philosophy, and public policy of alternatives to academia, government, industry, and the general public.
  • Educate and train in the application of alternatives.

*Alternatives are defined as new methods that refine existing tests by minimizing animal pain or distress, reduce animal usage, or replace whole animal tests.

To submit, please use the Preproposal Form. Full details here
 



Intersection of Chemistry and Toxicology

April 30, 2019
Washington, DC

Databases, software, machine learning, and online marketplaces are increasingly used by chemists and toxicologists to identify and/or design safer chemicals and materials. This day-long symposium is intended to provide CSW and NCAC-SOT members with updates on advancements in each of these tools, identify what improvements are needed, and discuss strategies for increasing worldwide adoption of such tools. Recognized experts from industry, NGOs, academia, and government will present their perspectives on this topic.

Thomas Hartung will present a talk on Read-across-based structure activity relationships (RASAR)—a new kid on the block of chemical safety assessment.

Registration and Information
 



EU-ToxRisk workshop: 
New Approach Method (NAM)-supported Read-across: from Case Studies to Regulatory Guidance in Safety Assessment

May 21-22, 2019
Espoo, Finland

Co-organized with ECHA, EFSA, NTP, EPA, OECD, and SCCS
 
The workshop is open to experts with interest and background into regulatory science coming from agencies, industry, and academia, providing an exceptional forum for discussion about the regulatory aspects of NAM-supported read-across. The meeting will focus on several scientifically advanced project case studies developed within the EU-ToxRisk project, the OECD/IATA program, and NIHS Japan and it will cover different regulatory contexts—both European (e.g. REACH, EU Pesticides) and global (Canada Chemicals Management Plan and Japanese Chemical Substances of Control Law).
 
The workshop outcomes will be included in an improved regulatory guidance document for NAM-supported read-across which EU-ToxRisk team plans to disseminate for the toxicological community. This will improve the quality of the submission of real read-across cases by registrants, and eventually increase the success rate of non-animal safety approaches.

Agenda and Registration
 
 
The EU-ToxRisk project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 681002.
 


Registration Now Open!
6th Symposium on Social Housing of Laboratory Animals

June 3-4, 2019
Beltsville, MD

In collaboration with USDA Animal Welfare Information Center, NIH Office of Laboratory Animal Welfare, and the Johns Hopkins Department of Molecular and Comparative Pathobiology

This symposium brings together experts in animal behavior and welfare to address common issues in trying to achieve the mandate for social housing for social species. Participants will be encouraged to discuss  special issues they are facing at their institutions. 

Program and Registration
 



Future of Endotoxins and Pyrogen Testing: Reference Standards and Procedures

June 10-11, 2019
Rockville, Maryland

The production of parenteral products requires not only that products be sterile, but that they are also free from harmful levels of pyrogens. Bacterial Endotoxins, components of the gram-negative bacterial cell wall comprise the vast majority of pyrogens found in parenteral manufacturing. For the last thirty-eight years, the predominant methods of evaluating parenteral products for the presence of bacterial endotoxins in vitro have been defined in the Bacterial Endotoxins Test. This assay is analytically calibrated against the USP Endotoxin RS. The in vivo evaluation of the Pyrogenicity, however, may be measured using the in vivo Pyrogen Test employing rabbits as outlined in Pyrogen Tests, USP, Bacterial Endotoxins Test, although now harmonized with the Japanese Pharmacopeia and the European Pharmacopeia since 2002, has remained essentially unchanged since its introduction in USP 20-NF 15 (1980). Recently there have been reports of interferences in recovery studies, as well as the appropriate utilization of endotoxin/pyrogen calibration standards and the potential use of alternative control standards. Also, there is increased interest in non-LAL test procedures or adaptation of alternative LAL analog methods in which the reagents are recombinant rather than derived directly from animals. Additionally, the recent uptick in the use of the Rabbit Pyrogen Test has been widely debated among stakeholders.

The USP Microbiology Expert Committee has developed this workshop to enable open objective discussions of practical and science-based issues evolving in endotoxin and pyrogen testing. The purpose of this workshop is to consider new reference endotoxin standards and the requirements for the inclusion of new endotoxins test methods in the near future.

Thomas Hartung will present a talk on "Non-Endotoxin Reference Materials for The Monocyte Activation Test (MAT)."

Information and Registration
 


EBTC Workshop: Application of Evidence-based Methods to Construct Mechanistic Frameworks for the Development and Use of Non-animal Toxicity Tests

June 12, 2019
McMaster University, Hamilton, Ontario, Canada

Systematic evidence synthesis methods and adverse outcome pathways are two relatively recent arrivals in the toxicologist's toolbox, which promise to bring toxicological research into the 21st Century.


Objectives

The goal of this workshop is to explore, via discussion of four related themes, how systematic review methods and AOP concepts can be combined to develop and use non-animal test methods for predicting the toxicity of chemical substances in an evidence-based manner.

1. How do we distinguish high quality in vitro studies from low quality ones?
2. What does a systematic approach to AOP development look like?
3. How does one distinguish spurious AOPs from plausible ones?
4. How can one use AOP information to develop non-animal toxicity assays?

Registration for this meeting is free and open to everyone; however, due to limited seating the organizing committee will have to make a final decision on participation depending on demand and the scientific objectives of the workshop. Please do not make any travel arrangements until you receive an official email confirming your attendance.

Registration and Information
 
 

Upcoming: CAAT-Europe Information Day On Biology-inspired Microphysiological Systems (MPS) to Advance Medicines for Patients' Benefit

June 17, 2019
Berlin, Germany
Co-organized with the Centre for Entrepreneurship (CfE) of the Technische Universität Berlin


The Information day on “Biology-inspired Microphysiological Systems (MPS) to Advance Medicines for Patients' Benefits” will host key international experts from academia, regulatory agencies, and industry.

Microfluidic microphysiological systems (also referred to as tissues-on-a-chip, organ-on-a-chip, multi-organ-chip, human-on-a-chip, body-on-a-chip, or patient-on-a-chip tools) are considered an enabling technology for the development of approaches to reliably predict the safety and efficacy of novel drug candidates prior to their use in humans. A transatlantic toxicology think tank involving academia, industries, and regulatory bodies from all over the world reviewed the status quo of MPS in June 2015 in Berlin (Marx et al 2016, ALTEX 33,272-321).  Now, four years later, stakeholders will meet again in Berlin to update the review and to examine the roadmap for the reduction and replacement of animals by MPS tools for precision benefits for patients. 
 
Full Details
 



 

It's Time to Think Outside the Cage: Charu Chandrasekera

Animal testing is largely disfavored globally, but the world is struggling to find alternatives. Dr. Charu Chandrasekera’s research has proven that there is not only a viable replacement, but one that is cheaper, faster, and more relevant to humans. Dr. Charu Chandrasekera is the founding executive director of Canada’s first and only research center dedicated exclusively to alternatives to animal testing—Canadian Centre for Alternatives to Animal Methods (CCAAM) and its subsidiary, the Canadian Centre for the Validation of Alternative Methods (CaCVAM)—officially launched at the University of Windsor in October 2017.

Watch the Video

 


EPAA Grants and Refinement Prize

3Rs Student Grants 2019: Call for Submissions

Every year, a number of high-profile international meetings bring together world-class scientists working on the development and acceptance of 3R alternatives to animal testing (Replacement, Reduction or Refinement). Costs linked to participation may prevent students with promising work from attending these events. The EPAA partners proudly sponsor the 3Rs Student grants to facilitate the participation of students in such events.

The jury will comprise 4 representatives of the EPAA Steering Committee (2 from the Industry and two from the European Commission) who will judge the applications. For each of the eligible events, a lump sum of €1500 is available. 2 levels of grants are offered by the EPAA partners: half grant and full grant.

  • A half grant covers the reimbursement of the event registration fees for the student as well as travel and accommodation fees, on the basis of the expense receipts up to a maximum of €500.
  • A full grant covers the reimbursement of the event registration fees for the student as well as travel and accommodation fees, up to a maximum total amount of €1000, on the basis of the expense receipts.
More Information

 

Refinement Prize 2019: Call for Submissions

The European Partnership for Alternative Approaches to Animal Testing (EPAA) is proud to announce its 2019 refinement prize. This prize of €6000 will be granted to a laboratory technician, animal care- taker or technologist who has demonstrated outstanding achievements in new, novel approaches to advance implementation and/or awareness raising of Refinement of animal testing.

Laboratory technicians, technologists and animal caretakers carry out much of the work using animals for regulatory safety and efficacy testing purposes and are thus closely involved in efforts to apply refinement strategies in such studies. Refinement is one of the 3Rs (replacement, reduction and refinement of testing on animals). Refinement refers to the modification of any procedure, husbandry and care practices with laboratory animals along their entire lifetime, to minimise pain and distress and enhance their well-being.

The purpose of this prize is to target those implementing alternative approaches to animal testing and/or raising awareness of their role for the day to day application and innovation of the refinement principles in particular.

The EPAA partners will sponsor a €6000 prize to be awarded in 2019. The prize can be applied for by an individual or a team. The money awarded is a prize, not a grant, therefore it does not require any prior justification of how it will be used. Nevertheless, the EPAA recommends linking its use to (further) promotion of alternatives, e.g. for travel and accommodation fees for a conference, publication costs, etc. The winner (or the winning team) will be invited to the EPAA annual conference in October 2019 to receive the prize and briefly describe his/her/their contribution to the 3Rs.

More Information
 


New Approach Methodology Use for Regulatory Application (NURA): Evaluating Toxicological Information Using Modern Science

May 21-22, 2019
Gaithersburg, MD

 
Companies submitting information to EPA under TSCA are learning how to incorporate New Approach Methodologies (NAMs). This knowledge is becoming valuable for FIFRA and other international regulations. Come familiarize yourself with how to incorporate these useful methods into your testing strategies, consulting, and safety assessments. PCRM and Institute For In Vitro Sciences (IIVS) have partnered with regulators, industry personnel, and toxicology experts to host another free training that you won’t want to miss.
 
Program highlights:
  • Expert presentations and demonstrations outlining currently available in vitro methods for skin sensitization, eye irritation, and more
  • Hands-on demonstrations with the latest QSAR, cheminformatics, and other computational tools
  • EPA’s implementation of the strategic plan for NAMs and the New Chemical Program
  • How to incorporate exposure assessment and green chemistry using NAMs
  • Contract organizations and consultants for NAMs
Registration and Information
 


11th World Congress on Alternatives and Animal Use in the Life Sciences 2020 (WC11)

WC11 will be held in Maastricht, the Netherlands from 23-27 August 2020. The general theme of the congress, "3Rs in transition: from development to application," emphasizes the increasing focus on the use of better, more human-relevant models for personalized and preventive health care, safer products, and innovative research.

WC11 will explore the latest in 3R R&D and will provide a multidisciplinary programme covering more traditional themes as well as very latest issues and novel developments in the field of alternatives to animal testing in the life sciences.

The Scientific Committee will set up the scientific program of the congress around four main themes:

  • Safety
  • Disease
  • Innovative technologies
  • Ethics and Welfare

These themes were defined to encourage the exchange of knowledge and ideas within and between research areas and sectors. In addition to the more traditional topics, WC11 will also cover cutting-edge issues and novel developments in 3Rs, including:

  • Recent developments in 3D cell technology, organ/body-on-chip approaches, advanced technologies for multi-scaled data generation from existing and new non-animal-based models
  • Translational research connecting in vitro results to the "real life" situation
  • Approaches for improving the effective use of existing data
  • Methods for increasing the efficiency of validation efforts of emerging 3Rs models for predicting efficacy and safety of new products
  • Marketing innovative 3Rs-based products and services: successes and pitfalls
  • Regulatory issues, societal acceptance and implementation

It is now possible to submit sessions for the scientific program through the online session form via www.wc11maastricht.org. The form is available from now on until June 30, 2019. 

Stay updated via the official website www.wc11maastricht.org and subscribe for our newsletter for important news and developments.

 



Best wishes from all of us,


The CAAT Team
     

hand holding centrifuge tubes

Upcoming Events

 
Intersection of Chemistry and Toxicology
April 30, 2019
Washington, DC

CellTox 2019
May 7, 2019
Milano, Italy

Biosystems Engineering: Bioreactors and Cell Factories
May 12-17, 2019
Braunweld, Switzerland
 
New Approach Methodology Use for Regulatory Application (NURA): Evaluating Toxicological Information Using Modern Science
May 21-22, 2019
Gaithersburg, MD

ALTERTOX Academy Training:
In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhalation Toxicology
May 23-24, 2019
Neuchatel, Switzerland

6th Symposium on Social Housing of Laboratory Animals
June 3-4, 2019
Beltsville, Maryland

Society for In Vitro Biology Annual Meeting
June 8-12, 2019
Tampa, Florida

Future of Endotoxins and Pyrogen Testing: Reference Standards and Procedures
June 10-11, 2019
Rockville, Maryland

Upcoming: CAAT-Europe Information Day On Biology-inspired Microphysiological Systems (MPS) to Advance Medicines for Patients' Benefit
June 17, 2019
Berlin, Germany

ALTERTOX Academy Training:
PBPK Modeling and Quantitative In Vitro-In Vivo Extrapolation
October 3-4, 2019
Wageningen, Netherlands

ALTERTOX Academy Training:
Novel In Silico Models for Assessment of Cosmetics
October 17-18, 2019
Milan, Italy

ALTERTOX Academy Training:
In Vitro Lung Models
November 14-15, 2019
Geneva, Switzerland

Save the Date!
5th International Conference on Alternatives for Developmental Neurotoxicity (DNT) Testing
February 3-5, 2020
Konstanz, Germany

Full Listing of CAAT Programs
and Activities

 

 

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