Development of Alternatives to Animal Use for Safety Testing and Hazard Assessment, continued.

Summary Problem Background/History Animal protection Toxicology and Safety Testing The Process of Change Implementation Definition	Motivation to Adopt In Vitro Testing and SAR: Two Models Obstacles to Implementation Validation International Controversy Current Challenges Literature Review/Bibliography
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Current Challenges

On October 9, 1998 the Clinton Administration, the Environmental Defense Fund and the Chemical Manufacturers’ Association jointly announced a six-year program to test 2800 major industrial chemicals for their health and environmental effects. This announcement followed three major studies which indicated that most industrial chemicals produced in high volume in the U.S. lack even the most rudimentary information on potential health effects (EDF, 1997; CMA, 1998; EPA, 1998) In an attempt to remedy this situation, chemical manufacturers have agreed to participate in a “voluntary challenge program” to provide basic toxicity information, a Screening Information Data Set (SIDS) on their High Production Volume (produced in greater quantities than 1 million pounds) or HPV chemicals. EPA will then pursue additional testing of chemicals believed to persist in the environment and exhibit cumulative effects on the health of human beings, animals and the environment. This program is based on the OECD’s SIDS program initiated a decade earlier, although the timetable for data accumulation and reporting has been much accelerated in the U.S. program.

The HPV program, one aspect of the Chemical Right to Know Initiative announced by Vice-President Al Gore on Earth Day 1998, has come under attack by a number of animal protection organizations, particularly People for the Ethical Treatment of Animals (PETA), which has initiated a campaign attacking the HVP program in general and Vice President Gore in particular. On February 24, 1999 PETA ran a full-page ad in The New York Times denouncing Gore and his support of the HPV and RTK testing programs. “If you think Al Gore is an environmentalist, think again. First he was caught in a secret White House memo supporting commercial whaling. Now he’s pushing a government program that will kill millions of birds, fish, rabbits and other animals in useless and painful experiments,” the ad read. “It may sound like something to vote for but it’s really just bad news for the environment, the animals and public health. Animal tests are so unreliable that they can actually clear chemicals we already know to be harmful to humans. Or, when animals die, companies can claim the results don’t apply. Either way, government action will be delayed for years. Modern, reliable, non-animal tests are available but are being ignored.”

On June 17, 1999, the House Committee on Science, Subcommittee on Energy and Environment, held its first hearing on the HPV Chemical Testing Program. The hearing was held three months after Science Committee Chairman F. James Sensenbrenner sent a letter to EPA director Carol M. Browner, requesting the agency’s response to ten questions on the methodological and scientific assumptions underlying the program. In his opening statement Ken Calvert, chair of the House energy and environment subcommittee, expressed his dissatisfaction with the EPA and their planned strategy in the strongest terms, questioning both the scientific assumptions upon which the program is based (“production quantity does not necessarily entail risk...there are certainly more serious threats posed by lower production, higher toxicity chemicals. Shouldn’t we focus on them ?”) and the methodologies which will be used to assess toxicity (“Significant doubt exists about the validity of animal testing results when applied to humans,” he said. “I would like to hear about some of the humane alternatives to animal testing.”) Calvert concluded his remarks by noting that “it might be better to go back to the drawing board on the HPV program, spend a little bit more time and apply some well-considered sound science to design a better chemical testing program.”

Meanwhile, the Johns Hopkins Center for Alternatives to Animal Testing, and its partners at the Environmental Defense Fund, University of Pittsburgh, and Carnegie-Mellon University, have adopted a policy termed “TestSmart,” characterized as a humane and efficient approach to acquiring SIDS Data. “The immediate objective is to reduce the number of animals tested by incorporating in vitro and other alternatives into the SIDS battery of tests. Our long-term goal is to provide a more humane and efficient model for collecting data for hazard evaluation and safety assessment,” the program literature states. “In the long run, we believe appropriate molecular-based, mechanistic assays can be developed that will lead to a more accurate assessment of chemicals--and to a safer environment for the public.” CAAT held a TestSmart workshop on April 26-17, 1999 in Fairfax, VA. Participants included representatives of the Environmental Defense Fund, OECD, EPA, Humane Society of the United States, PETA, Physicians Committee for Responsible Medicine, National Institute of Environmental Health Sciences, Food and Drug Administration, ICCVAM, ECVAM and various academic researchers creating new testing methodologies, including the use of human cells in culture.

Workshop participants created a list of recommendations which included the following goals:

1) Reduction and refinement alternatives for acute toxicity testing should be incorporated, including the fixed dose procedure, the up-and-down procedure, the acute toxic class method and the limit test. (Each of these uses far fewer animals than traditional methods of acute toxicity testing and avoids death as an endpoint).

2) Existing in vitro tests for genetic toxicity should be employed immediately. These include the Ames-Salmonella and mouse lymphoma assays for bacterial and mammalian mutations and the Chinese Hamster Ovary cell assay for chromosomal aberrations.

3) In vitro tests evaluating sperm motility and sperm morphology should be used to screen for reproductive toxicity and SAR (structure-activity relationships) to establish chemical categories and to select specific chemicals within categories.

5) Promising in vitro tests should be evaluated as soon as possible and incorporated into the testing process. Potential candidates include the in vitro micronucleus assay for genetic toxicity, the FETAX, limb bud, and whole embryo culture assays for developmental toxicity and the basal cytotoxicity and neutral red uptake assays for acute toxicity.

The group also identified several promising areas worthy of additional research, including the use of organ cell cultures, human cells and tissue, and identification of mechanistic endpoints for toxicity screening. The full list of recommendations from this workshop and an explanation of the TESTSMART initiative are available on the ALTWEB site: http://altweb.jhsph.edu

TestSmart represents the continued effort to find common ground between scientists, regulatory officials and the activist community (environmental and animal protection). As in the earlier conflict over cosmetic testing, TestSmart offers a centrist approach, one which recognizes the validity of opposing viewpoints and seeks to create humane and efficient alternatives. Although the motivation of individuals adopting these principles may differ, a commitment to the goals of replacement, reduction and refinement offers a way to overcome the kind of protracted and pointless confrontation which serves neither human or animal well-being.

The TestSmart approach is being adopted by other groups and programs and may serve as a model for future efforts to achieve regulatory change. Those individuals and organizations who have adopted this model believe that in doing so they are following in the footsteps of Henry Spira, the activist whose efforts led to the founding of CAAT. “Rather than daydreaming about perfect solutions, activists need to push for the most rapid progress that can be realistically achieved,” Spira wrote in “Blueprint for Change,” first published in 1994 and reprinted in his 1997 guide, Strategies for Activists. Writing for activists who wish to promote corporate and government change, Spira (who died in September 1998) advised: “Keep building on previous achievements. Aim for initiatives that grow and proliferate, and become self-sustaining. It is an enterprise that develops a life of its own. Each action, each event is a step forward. And with each step forward, you can look further ahead.”

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