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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Background/History:

The modern animal rights movement is a product of two converging strains of modern thought regarding the role and status of animals and the human relationship to animals. The first, epitomized in the humane movement, sought to improve treatment of animals in a number of different areas without challenging the inherent right of humans to use animals as sources of food, labor, clothing and entertainment. The American Society for the Prevention of Cruelty to Animals (ASPCA), founded by Henry Bergh in 1866, was the first formal group established in the U.S. to work for better conditions for animals. While attempting to build support for the founding of the group, Bergh gave a lecture in New York City in which he noted that the prevention of animal cruelty “is a matter purely of conscience...it is a moral question in all its aspects; it addresses itself to that quality of our nature which cannot be disregarded by any people with safety to the dearest interests. It is a solemn recognition of that greatest attribute of the Almighty Ruler of the universe, mercy, which if suspended in our own case for a single instant, would overwhelm and destroy us.” (Niven, 1967)

Soon after founding the ASPCA, Bergh successfully lobbied for the passage of the nation’s first anticruelty law passed by the New York State legislature in April 1866. The work of the ASPCA was soon taken up by a number of other state and local humane societies which shared its commitment to improving the quality of lives of animals used by humans for a broad range of uses. Bergh and the humane societies stressed the important role that animals played in human society and the need for society to protect them. (Loeper, 1991;Turner, 1980)

A second strain of nineteenth century animal protection activity was far more radical than that championed by the ASPCA and other humane groups and focused exclusively on the use of animals as the subjects of scientific research. The antivivisection movement was adamantly opposed to such research and worked to abolish the use of animals in science. Bergh himself was an antivivisectionist, however after his death the ASPCA retreated from a pure antivivisectionist position and adopted a more moderate posture--seeking to limit abuses but in general accepting the need for animals to be used in science, as they were used for labor and food. The American Antivivisection Society, founded by Caroline Earle White in 1883, was the first formal group championing the antivivisection cause founded in the U.S. White had previously helped found the Pennsylvania Society for the Prevention of Cruelty to Animals in 1867. The founding of the AAVS was followed by the establishment of other state and local antivivisection societies throughout the United States. (Lederer, 1987 and 1995)

Although the humane movement was able to exert a certain degree of influence as an advocate for animals throughout the next hundred years, the antivivisection movement withered as scientists began to discover the causes, cure and prevention of various human diseases as a result of animal research. As the power of the scientific community grew, the influence of the antivivisectionists waned. However, by the 1970’s certain key events initiated a rebirth of the antivivisection movement under a new name--animal rights. Although the animal rights movement has a much broader agenda than simple antivivisection, its first targets were scientists and the use of animals for scientific research, and its first successes, which led to a massive growth in numbers and influence, were led by antivivisectionists.

The intellectual underpinnings of the modern animal rights movement have been provided by philosophers Peter Singer and Tom Regan. Singer, the author of Animal Liberation, published in 1975, is often called the father of the modern animal rights movement although his utilitarian philosophy does permit some limited use of animals. Tom Regan, author of The Case for Animal Rights, published in 1983, promotes a more pure philosophy of animal rights advocating the complete abolition of all forms of animal use. In this latter view, all human uses of animals are exploitative and oppressive in that they violate an animal’s right to exist free of human predation. It is important to note that even prior to the publication of Singer and Regan’s books, certain individuals and organizations, particularly in England, had already begun to operate according to animal rights principles, propounding a philosophy of animal “liberation” (Finsen & Finsen, 1998; Garner, 1993). However, it was not until the publication of these and other philosophical justifications, particularly Singer’s Animal Liberation, that the movement began to receive serious consideration and to recruit large numbers of adherents.

Although human beings have long sought to evaluate the hazards of various substances, both natural and manmade, by first testing their effect on animal or human “tasters,” (including condemned prisoners) the establishment of a science of toxicology, or the systematic study of toxins, is a relatively recent development. Both pharmacology and toxicology were born as experimental sciences in the nineteenth century. It is interesting to note that both sciences were, from their inception, inextricably entwined with the growth of animal experimentation, and thus “from their very beginnings were confronted by opposition to vivisection experiments.” (Parascandola, 1991).

The first law in the United States mandating testing of consumer products was the Food, Drug and Cosmetic Act passed by Congress in 1938. This legislation was enacted after a series of accidents in which Americans were harmed by various drugs and cosmetics, including the death by poisoning of 107 Americans by a contaminated drug preparation called Elixir of Sulfanilimide, and severe eye injuries caused by a eyebrow/eyelash dye named Lash-Lure (Lamb, 1936). Although earlier legislation had prohibited interstate commerce of adulterated food, drink and drugs (Green and Bradlaw, 1992), they did not require safety testing or mandate that the manufacturer establish tolerance levels for these substances. John Draize, a pharmacologist who had previously researched the effects of agents used in chemical warfare, was hired by the FDA to develop eye and skin tests to determine the safety of cosmetic products.

“The FDC Act of 1938 established the concept that the cosmetic manufacturer must substantiate the safety of ingredients and finished products prior to marketing the product. Under the law, any ingredient or product whose safety is not adequately substantiated prior to marketing is inadequately labeled (i.e. misbranded) unless it is labeled with the statement ‘The safety of this product has not been determined,’ wrote James P. McCulley and Thomas J. Stephens in 1993. “Interestingly, the authors of the Act did not specify the types of tests required to substantiate the safety of products. This wording was not an accident. They undoubtedly expected the methods of testing to improve with time and did not want the law to specify outdated test methods.” (McCulley & Stephens, 1993).

Twenty years after the passage of the Food, Drug and Cosmetic Act, Congress passed the Delaney Amendments to the Act, which required that manufacturers furnish data proving that their products did not cause cancer. The Delaney amendments resulted in a much increased use of laboratory animals, particularly rodents, as manufacturers attempted to meet the requirements of the law. In 1976, Congress passed the Toxic Substances Control Act which gave the U.S. Environmental Protection Agency the authority to require testing of potentially harmful substances and the power to ban or restrict the manufacture or use of any chemical deemed hazardous. A number of other government regulatory agencies also either began to conduct testing themselves or to require tests of the products they were responsible for regulating. “As public pressures to protect the consumer heightened, additional legislation in the 1950’s and 1960’s introduced or strengthened regulations concerning the premarket testing of food additives, color additives, insecticides, drugs, and other products. At the same time, concerns about toxins in the environment and in the workplace led to further legislation concerning the testing and control of toxic substances. These developments contributed to a significant increase in toxicity testing, most of it involving the use of animals.” (Parascandola, 1991)

Traditional toxicology is based upon the assumption that physiological processes in mammals are much the same and that a substance which is toxic to a small mammal like a rodent is likely to prove equally toxic to a human being, if the quantity of the substance is adjusted according to body weight and other factors. Early tests mirror the concerns of the time. For example, in the wake of the cosmetics scare in the 1930’s, the Draize tests for eye and skin irritation were developed. The LD50, a test developed in 1927 to measure the potency of biological preparations such as vaccines was converted to use as a predictor of acute toxicity, establishing the lethal dose of a drug, chemical or other product. The LD50 assesses acute oral toxicity, and provides an estimate of the quantity of a substance which will kill half the members of a test population. Like the Draize test, the LD50 has been the focus of much criticism by both scientists and animal protectionists who object to exposing animals to high doses of toxic substances. This approach has been dubbed by critics the “kill ‘em and count ‘em” school of testing.Tests developed in the wake of the Delaney amendments, sought to establish the possible effects of continuous exposure to potential toxins (chronic toxicity) and a range of other biological effects, including effects on the reproductive, nervous and endocrine systems. Most of these tests also used large numbers of animals and generally used death or extreme morbidity as endpoints.

All of these are aspects of risk assessment, the process by which substances are evaluated for their potential impact on human health and safety. Risk assessment can be subdivided into two categories--assessment of exposure, which is an estimate of the number of people who may be exposed to a particular chemical, plus concentration, duration and terms of exposure--and toxicity testing, which identifies hazards. Toxicity testing is also expected to predict the type of adverse effects which may follow exposure to a chemical and provide an estimate of the exposure-response relationship. Many factors may affect the latter, including age, sex, genetic background, and health status of the subject.