Alternatives In Testing

“There is no doubt that the best test species for humans are humans. It is not possible to extrapolate animal data directly to humans due to interspecies variation in anatomy, physiology and biochemistry.”[1]

To predict toxicity, corrosivity, and other safety variables as well as the effectiveness of a new product for humans, traditional testing of chemicals, consumer products, medical devices, and new drugs has involved the use of animals. But today, scientists have developed and validated alternative methods shown to lead to safer and more effective products and drugs for humans than animal testing.

For example, skin corrosivity and irritation can be easily measured using three-dimensional human skin equivalent systems such as EpiDerm and SkinEthic. Additional alternatives include EpiSkin (a model of reconstructed human epithelium) and a variety of sophisticated, computer-based Quantitative Structure Activity Relationship (QSAR) models that predict skin corrosivity and irritation by means of correlating a new drug or chemical with its likely activity, properties, and effects with classification accuracy between 90 and 95 percent[2].

Some alternatives to the use of animals in testing include

  • in vitro (test tube) test methods and models based on human cell and tissue cultures
  • computerized patient-drug databases and virtual drug trials
  • computer models and simulations
  • stem cell and genetic testing methods
  • non-invasive imaging techniques such as MRIs and CT Scans
  • microdosing (in which humans are given very low quantities of a drug to test the effects on the body on the cellular level, without affecting the whole body system)

Benefits of non-animal testing

  1. Alternative scientific tests are often more reliable than animal tests.

For example, experiments on rats, hamsters, guinea pigs, mice, monkeys, and baboons revealed no link between glass fibers and cancer. Only after human studies related the two did the Occupational Safety and Health Administration (OSHA) label these fibers as carcinogenic. EpiDerm, an in vitro test derived from cultured human skin cells, was found to be more accurate in identifying chemical skin irritants than traditional animal tests. In comparison studies, EpiDerm correctly detected all of the test chemicals that irritate human skin, while tests on rabbits misclassified 10 out of 25 test chemicals—a full 40% error rate.

  1. The use of human tissue in toxicity testing is more accurate than the animal models.

The “Lethal Dose 50” (LD50) test forces animals to ingest toxic and lethal substances to the endpoint of where 50% of the animals in the study die—and those that do not are later killed. The late Dr. Bjӧrn Ekwall (Cytotoxicology Laboratory in Sweden) developed a replacement for the LD50 test that measured toxicity at a precision rate of up to 85% accuracy compared to the LD50 rate of 61-65%. This test, far more accurate than the animal models, uses donated human tissue rather than animal. Further, the test can target toxic effects on specific human organs, whether or not the toxic substance permeates the blood barrier, and other highly sophisticated and precise information that the agonizing death of an animal of a different species would not reveal.

  1. Non-animal tests are more cost-effective, practical, and expedient.

InVitro International’s Corrositex (synthetic skin) can provide a chemical corrosivity determination in as little as 3 minutes to four hours, unlike animal testing that often takes two to four weeks. DakDak, an alternative test used to measure the effectiveness of sunscreens, was reported to do in days what it takes animal studies months to do, and estimates that it can test five or six products for less than half the cost to study a single product in animals. The traditional testing of chemicals using animals can take up to five years per substance and cost millions of dollars, while non-animal alternatives can test hundreds of chemicals in a week for a fraction of the cost.

  1. Cruelty-free products are more environmentally friendly.

In toxicity testing, researchers breed, test, and ultimately dispose of millions of animals as pathogenic or hazardous waste. Cruelty-free testing is less harmful to the environment or creates less waste.

In 2007, the U.S. National Research Council (NRC) released a report titled “Toxicity Testing in the 21st Century: A Vision and a Strategy,” which addressed the limitations of animal-based toxicology tests and called for a shift toward non-animal, human-based testing methods. The report was issued in response to a request from the U.S. Environmental Protection Agency (EPA), asking for the NRC to conduct a comprehensive review of toxicity testing methods. In their report, the NRC summarized that “[a]dvances in toxicogenomics, bioinformatics, systems biology, epigenetics, and computational toxicology could transform a system based on whole-animal testing to one founded primarily on in vitro methods that evaluate changes in biologic processes using cells, cell lines, or cellular components, preferable of human origin.”[3]

In 2008, the EPA and the NIH’s National Toxicology Program and Chemical Genomics Center signed a “Memorandum of Understanding” to follow the NRC report’s vision and begin developing new methods of toxicity testing that involve the use of lab grown human cells instead of animals. After the EPA began evaluating 300 chemicals using the new methods, they found that it allows for thousands of chemicals to be tested at once. This method is much faster, less expensive, and does a better job of protecting human health. According to former NIH Director Elias Zerhouni, “It won’t mean that animal testing will disappear overnight, but it signals the beginning of the end.” Today, the EPA is in the process of building virtual human organs. The EPA's "virtual tissue" researchers are developing a set of computer simulations that may one day be able to identify the risks posed by common industrial pollutants such as pesticides, saving thousands of animals from horrific toxicity tests.[4]

ICCVAM

The need for alternatives to the traditional use of animals in toxicity testing was officially recognized by the U.S. government in 1993 with passage of the NIH Reauthorization Act. Requirements under the Act led to the establishment of an ad hoc committee called the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM). ICCVAM was made a permanent committee under the ICCVAM Authorization Act of 2000 and is composed of representatives from 15 U.S. federal regulatory and research agencies.

Under the National Toxicology Program’s Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), ICCVAM’s mission is “to promote the development, validation, and regulatory acceptance of new, revised, and alternative regulatory safety testing methods. Emphasis is on alternative methods that will reduce, refine (less pain and distress), and replace the use of animals in testing while maintaining and promoting scientific quality and the protection of human health, animal health, and the environment.”[5]

Conclusion

As science continues to transform our world beyond what we know, and technology continues to transform and expand upon what we depend on as our “rule of thumb,” medical research and testing will also transition to embrace and depend on alternatives rather than the use of animals. In fact, three states (CA, NJ, NY,) have already passed legislation mandating that federally approved non-animal alternatives, when available, be used for product testing in place of animals. Additionally, the Mandatory Alternatives Petition (MAP) coalition (of which NEAVS is a founding member) submitted a scientific petition to the U.S. Food and Drug Administration (FDA) requesting that instead of using animals, pharmaceutical companies, device manufacturers, and other entities regulated by the FDA must use validated non-animal methods whenever they exist. If accepted, such a mandate would change the way industry meets requirements to show drug and product safety for humans thus sparing tens of millions of animals from horrific testing and death. After consideration of the petition, the FDA is currently developing (with MAP input) better policy guidelines that will make it clear that animal tests are not required to meet FDA criteria for safety and efficacy—a partial but significant accomplishment of the MAP.

Science—fueled by the work of scientists themselves as well as by public demand for more humane science—is moving toward the day when cruelty-free research and testing will be the status quo. Science can and must protect animals’ lives, the environment, research dollars, and promote better health and well-being for humans. Science, thanks to modern technologies, is finally moving forward to realize the premise that the “best test species for humans are humans”—without harm and with enormous benefit to humans.


[1] MacLennan & Amos. (1990). Clinical Science Research Ltd., UK, Cosmetics and Toiletries Manufacturers and Suppliers, XVII, 24.

[2] European Commission. (n.d.). Joint Research Centre: QSAR Review Irritation.

[3] National Research Council. (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. Washington, DC: The National Academies Press.

[4] Johns Hopkins University. (n.d.). EPA Developing "Virtual Liver" Computer Simulation.

[5] National Toxicology Program. (n.d.). NICEATM - ICCVAM, Frequently Asked Questions.

[6] Ibid.

 

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