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

Dialogue and cooperative efforts between industry, government regulatory agencies, academic scientists and animal protection organizations have produced a workable strategy to replace, reduce and refine the use of animals for safety testing and hazard assessment. Over the past twenty years, animal use in one industry (cosmetics and personal care products) has been greatly reduced. Other industries are currently facing challenges similar to those confronted by the cosmetics industry in the past and might benefit from actively pursuing the 3Rs (replacement, reduction, refinement) approach, which integrates concern for animal welfare with a commitment to progressive scientific policy and practice.

Development of testing methodologies which are both more predictive of human response to a broad range of chemicals and finished products and less costly in animal lives and suffering.

Since the passage of the Food, Drug and Cosmetic Act and other legislation meant to assure human health and safety via mandated testing of consumer products and chemicals, animals have been used as test subjects. Over the past sixty years, a broad range of animal tests has been developed to predict possible adverse effects of chemical ingredients and finished products. Some of the first tests to be developed and required by regulatory agencies in the U.S. and throughout the world included the Draize tests for eye and skin irritation and the LD50 test for acute toxicity. Other tests to assess carcinogenicity (ability to cause cancer), genotoxicity (ability to damage genetic material), reproductive toxicity (ability to harm the developing fetus or organs of reproduction), neurotoxicity (effect on the brain and nervous system), and other adverse effects swiftly followed. By 1975, a broad range of tests requiring large numbers of animals were recommended by the Organization for Economic Cooperation and Development (OECD), whose 29 member countries produce two-thirds of the world’s good and services, to establish the safety of products.

Nonetheless, developments within science were causing some to question the validity and usefulness of some animal tests. For example, in 1976, Swiss toxicologist Gerhard Zbinden, then director of the Institute of Toxicology at the University of Zurich, charged that the LD50, a test used worldwide to establish acute toxicity by determining the amount of a substance required to kill half a population of fifty to two hundred test animals, was “a wasteful endeavor in which scientific inventiveness and common sense have been replaced by a thoughtless completion of senseless protocols.” A few years later, Zbinden further alleged that the clinical experience indicated that the LD50 value in animals “rarely bears a meaningful relation with the lethal dose in man.”

In an 1989 article titled “Environmental Pollution and Cancer: Some Misconceptions” Bruce N. Ames, director of Environmental Health Sciences at the University of California, Berkeley and Lois Swirsky Gold, staff scientist at the Lawrence Berkeley Laboratory and director of the Carcinogenic Potency Project, stated unequivocally that “animal cancer tests conducted at near-toxic doses of the test chemical cannot predict the cancer risk to humans at the much lower doses to which they are typically exposed. The prediction of cancer risk requires knowledge of the mechanisms of carcinogenesis...recent understanding of these mechanisms undermines many of the assumptions of current regulatory policy regarding rodent carcinogens and requires a reevaluation of the purpose of routine animal cancer tests.”

The same problem was evident in animal tests for teratogenicity, Ames and Gold indicated, when test animals were fed doses of chemicals which far exceeded the amount of a chemical to which humans were naturally exposed. “Alcohol is the most important known human chemical teratogen. In contrast, there is no persuasive evidence that TCDD (dioxin) is either carcinogenic or teratogenic in humans, although it is both in rodents at near toxic doses. If one compares the potential of TCDD for causing birth defects with that of alcohol (after adjusting for their relative potency as determined in rodent tests) then daily consumption of TCDD at the EPA reference dose (the allowable dose) would be equivalent in teratogenic potential to a daily consumption of alcohol from 1/300,000 of a beer. That is equivalent to drinking a single beer (15 g ethyl alcohol) over a period of 8,000 years.”

At the same time that some scientists were instituting a critique of commonly performed protocols and their impact on regulatory policy, a social movement interrogating the human use and treatment of animals began to assert moral and ethical objections to the use of animals for product safety testing. This movement, although apparently appearing de novo in the middle decades of the twentieth century, nonetheless expressed longstanding objections to the scientific study of animal physiology through vivisection (French, 1975; Lansbury, 1985; Orlans, 1993; Rupke, 1990; Vyvan, 1969). By 1971, the number of animals used in scientific research and testing throughout the world exceeded 100 million, with at least 51 million animals per year used in research and testing in the United States alone (Rowan, 1984). Rats and mice comprised the great majority of laboratory animals, but dogs, cats, rabbits, hamsters, guinea pigs, birds, frogs and primates were also commonly used as research subjects.

Within a relatively brief period of time in the early 1980’s, the animal rights movement was able to mobilize large numbers of Americans who objected to the practice of animal testing, particularly of cosmetics. Movement leaders were quick to seize upon cosmetics as a particularly effective tool to illustrate both the suffering of animals used as test subjects for eye and skin irritation, and the apparently trivial cause of their suffering--the development of lipsticks, skin creams, and other nonessential items. (Blum, 1994; Jasper & Nelkin, 1992; Rowan, Loew & Weer, 1995) For example, the Draize test for eye irritation was viewed by many animal advocates as a particularly egregious example of cruelty, although it was viewed as a scientific advance when developed in the nineteen forties. In the standard Draize test, a test substance was placed in one eye of a group of rabbits. The rabbits’ eyes were inspected periodically (usually at 24, 48 and 72 hours and at 4 and 7 days) after administration of the test substance and scientists observed and quantified changes in the cornea, conjunctiva and iris. Recovery from damage was also observed and measured. Animal protectionists argued that the test was both scientifically crude and cruel. Some scientists (Smyth, 1978; Weil and Scala, 1971) also supported replacement of the test, but in 1980 the great majority of toxicologists and regulatory officials maintained that the test, despite its acknowledged flaws, was both useful and necessary because it provided some basis for standardization and quantification of a product’s potential for irritation and more serious damage to the eye.

Although the limitations of available testing practices were increasingly evident, reformers were confronted with a dilemma. Although some scientists were willing to admit that available tests were inadequate, in 1978, few non-animal tests were available (notwithstanding Bruce Ames’ development of a bacterial test for mutagenicity in 1971). It was clear that the traditional protocols would never be replaced without a concerted effort to develop new tests. Such an endeavor would require large sums of money for research and a long-term commitment by key stakeholders to what would likely be a protracted and contentious transition from animal tests to “alternatives.” This has indeed been the case. The commitment of the cosmetics industry, fueled by consumer objections to animal testing, has created large-scale insitutional change. By 1999 an international effort to develop, validate and implement alternatives to animal use in other areas is also underway.

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