In addition to the 3Rs advancement efforts by US federal agencies and NICEATM/ICCVAM, several independent nonprofit and academic centers also operate with similar mandates. These include:

• Alternatives Research & Development Foundation
• American Society for Cellular and Computational Toxicology
• Human Toxicology Project Consortium
• Institute for In Vitro Sciences
• International (Q)SAR Foundation
• Johns Hopkins Center for Alternatives to Animal Testing
• University of California at Davis Center for Animal Alternatives Information

Alternatives Research & Development Foundation

The Alternatives Research & Development Foundation (ARDF) was established by the American Anti-Vivisection Society in 1993 to provide an independent vehicle for its non-animal alternatives research funding program. The stated ARDF mission is to fund and promote the development, validation, and adoption of non-animal methods in biomedical research, product testing, and education. Since its inception, ARDF has provided more than $2.5 million dollars in direct funding of alternatives research.

Recent awards with potential relevance to regulatory toxicology include the following:

• In vitro model for cytotoxicity using mouse embryonic stem cells (2007)
• Human oligodendrocytes derived from embryonic stem cells for in vitro assessment of neurotoxicity (2007)
• Human embryonic stem cell model to predict neural tube birth defects (2007)
• A novel human mini-liver model for studying drug toxicity (2008)
• Multianalyte microphysiometry of human cell lines to replace animal toxicology (2008)
• Cellular and enzymatic microarrays to reduce the use of animals in toxicology studies (2009)
• Development of virtual rat liver for pharmacological and toxicological investigations (2010)
• Medical device testing in human blood vessel mimics (2010)
• Human blood vessel mimics as in vitro aneurysm models for evaluation of endovascular devices (2011)
• An in vitro model of human breast cancer metastasis (2012)

ARDF also funds educational activities that advance alternatives, sponsors scientific meetings such as the World Congresses on Alternatives and Animal Use in the Life Sciences, and supports the online alternatives resource sites, AltTox and Altweb.  The William and Eleanor Cave Award is made by ARDF  in recognition of scientists “who have made extraordinary contributions to the advancement of alternatives.”

In addition to its funding programs, ARDF advocates for public policy that advances alternatives. For example, having funded successful development of a practical in vitro alternative to the animal-based ascites production of monoclonal antibodies, ARDF petitioned the National Institutes of Health (NIH) in 1997-98 for a ban on the ascites method. While NIH did not agree to the ban, it informed all NIH-funded research facilities that in vitro monoclonal antibody production was to be considered the default method, with justification required for the use of animals.

American Society for Cellular and Computational Toxicology

The American Society for Cellular and Computational Toxicology (ASCCT) was established as a non-profit scientific society in 2010 by the Institute for In Vitro Sciences and the Physicians Committee for Responsible Medicine to promote the development and use of nonanimal toxicological testing methods.

Through regular meetings and activities, the Society aspires to facilitate the development, acceptance, and routine use of cellular and computational methods by open dialog between industry, academic, advocacy, and regulatory scientists.
The first meeting of ASCCT, held in Bethesda, Maryland in September 2012, was summarized in a recent issue of the AltTox Digest.

Human Toxicology Project Consortium

The Human Toxicology Project Consortium (HTPC) is a group of stakeholder organizations that “share the objective of accelerating implementation of the vision in the National Research Council’s 2007 report on Toxicity Testing in the 21st Century

The paradigm shift described in the NRC report is taking root via several large-scale efforts, primarily in the US and Europe, for example:  Tox21, a US government-sponsored collaboration between the Environmental Protection Agency, Food and Drug Administration, and the National Institute of Environmental Health Sciences, and several Framework Programme projects co-sponsored by the European Commission and industry, including Safety Evaluation Ultimately Replacing Animal Testing (SEURAT).  The Consortium aims to accelerate implementation of methods that result from these and other efforts by providing complementary support in 3 key areas:  1) addressing critical scientific needs not covered by current efforts, 2) communication with stakeholders including non-governmental organizations, government officials and the public, 3) providing an independent venue for lobbying and fundraising to support pathway-based science and policies.

The HTPC held their first workshop in Washington, DC on November 9-10, 2010. Speakers at this workshop, “Accelerating Implementation of the National Research Council Vision for Toxicity Testing in the 21st Century,” described current programs in the US and EU, and proposed innovative and collaborative approaches for moving the “vision” forward. The workshop summary is published in Toxicological Sciences. An AltTox article, “Accelerating the National Research Council Vision for 21st Century Toxicology,” provides additional details on the goals of the HTPC and outcomes of this workshop.

Institute for In Vitro Sciences, Inc.

The Institute for In Vitro Sciences (IIVS) in Gaithersburg, Maryland, is a technology-driven, nonprofit organization created to advance the development, validation, and use of in vitro methods in toxicology.

Since its founding in 1997, IIVS has come to be recognized as a leading national and international authority on the 3Rs and toxicity testing through the following program activities:

• Contract testing services: provide quality in vitro toxicity testing for a broad range of industry and government sectors in the areas of skin and eye irritation/corrosivity, phototoxicity, embryotoxicity, percutaneous absorption, basal cytotoxicity, and other specialized areas.
• Assay development and validation: provide assay optimization services and experienced management of validation projects. IIVS has served as a participating laboratory in numerous prevalidation and validation studies, and participated in the European Union integrated project ACuteTox.
• Education and training: provide clients and other stakeholders with a range of education and training opportunities, including hands-on practical demonstrations designed for new users, as well as more involved ‘technical workshops’ and ‘user groups’ of experts in a particular assay. The goal of these outreach efforts is “to improve and expedite in vitro method development and validation through cooperation, exchange of information, and training.”
• Advocacy: participate in national and international efforts to promote the validation and acceptance of in vitro toxicity test methods, which includes IIVS scientist appointments to ICCVAM and ECVAM advisory committees and other international scientific task forces.

International (Q)SAR Foundation

Established in 2004 by a former US Environmental Protection Agency senior scientist and program manager, the International (Q)SAR Foundation (IQF) is a nonprofit research entity working to develop quantitative structure-activity relationship [(Q)SAR] and other in silico models as non-animal alternatives for identifying chemical hazards. The stated mission of the IQF is to “develop computerized tools as alternatives to animal testing in order to decrease our reliance on animal tests in regulation, research and education.” The goals of IQF include demonstrating “the reliability of (Q)SAR-based methods in hazard identification.”

Activities of the IQF include the organization of workshops, support of various research projects, and providing access to relevant software, databases, and training. Central to the foundation’s mission is the organization of focused workshops to bring together experts from the regulatory, regulated, and other stakeholder communities to identify barriers to alternative approaches, as well as priorities for research to overcome these barriers. The topics of recent workshops include reactive toxicity, aquatic toxicity, and predictive toxicology. The IQF also supports and collaborates on various research projects including: (Q)SAR for inhalation toxicity in mammals, (Q)SAR for aquatic toxicity of reactive chemicals, (Q)SAR for classification of skin/lung sensitization, and more.

Johns Hopkins Center for Alternatives to Animal Testing

The Center for Alternatives to Animal Testing (CAAT) is “an international, non-profit organization dedicated to improving health for both people and animals.” The goal of CAAT is to “promote humane science by supporting the creation, development, validation, and use of alternatives to animals in research, product safety testing, and education.”

CAAT was established in 1981 by Alan Goldberg at the Johns Hopkins University Bloomberg School of Public Health (Baltimore, Maryland). Dr. Goldberg served as the Director of CAAT for over 25 years.

In 2009, Thomas Hartung, former Director of the European Centre for the Validation of Alternative Methods (ECVAM), was appointed as the second Director of CAAT. CAAT continues to grow and evolve, and in 2010 established the new European center, CAAT-Europe at the University of Konstanz, Germany.

CAAT’s 3Rs activities include providing research grants and 3Rs awards; organizing and sponsoring numerous international workshops and symposia; conducting a robust research program; providing educational courses and programs; and providing 3Rs information through the alternatives information website, Altweb, as well as the journal ALTEX: Alternatives to Animal Experimentation.

University of California at Davis Center for Animal Alternatives Information

Based at the University of California at Davis (UCD), the UCD Center for Animal Alternatives Information operates principally as an information resource for university administrators, scientists, students, and others with an interest in animal welfare and the 3Rs.

Specific objectives of the center are described by the Center as follows:

• To act as coordinating office for the UCD campus on improved and alternative methods for the use of animals and to coordinate a program of information and dissemination regarding approaches for alternative methods and the sharing of written and electronic materials and information
• To create, maintain and provide access to up-to-date resources and library materials on animal alternatives that are easily accessible to UC faculty, staff and students
• To offer outreach and educational activities regarding new developments in animal alternatives, providing leadership to the public and other educational institutions
• Within the context of the responsible conduct of science, to create a forum for discussion of ethical issues and dilemmas involving animal use
• To encourage use of teaching methods and materials incorporating alternatives at all educational levels

The center’s website includes resources such as a guide to relevant databases, tips on appropriate literature reviews, alternatives in education, humane endpoints, and more.