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Reliability of Animal Data
Reliability of Animal Data
‘In the absence of human data, research with experimental animals is the most reliable means of detecting important toxic properties of chemical substances and for estimating risks to human and environmental health.’
What Is Necessary for Basic Research and Safety Testing?
Scientists need to study natural situations to understand life processes and to investigate how introducing a particular substance can change living systems. It is often helpful to break a process into steps and then investigate how introduction of the substance affects each step. This first stage in toxicity assessment takes place in vitro. The investigator can pinpoint the various changes that could occur when a compound encounters a living cell and then make safety recommendations. Only a few substances successfully pass these initial trials. Those substances must then be tested further. Humans and other living things—plants, animals, and even molds and bacteria—are complex systems. The processes in any organism are far more complicated than just the sum of the individual parts. It is difficult to replicate at the lab bench the complex interactions. When safety is not assured, ethical research procedures restrict testing on humans. Additional experiments must be performed using other animals first.
Many complex interactions with a chemical can occur
that can only be detected in a living organism. |
Why Is There a Need to Use Animals?
All organisms are composed of chemicals, and chemical reactions power all life processes. When a substance is introduced into an animal, it can interact in many places throughout the whole body, and effects upon one process can cause unexpected consequences in others (see diagram). Using animals in experiments is critical because such complexity cannot be duplicated in cell culture or in nonliving systems. For example, toxicity can be influenced by the speed with which the substance enters the system, how the liver and other organs change it and how it is taken up by and interacts with various body tissues. Some of the response is influenced by the tissue characteristics (e.g., liver is different than kidney tissue). Because “the dose makes the poison” at the level of the individual organ, we need to be able to analyze not only how a chemical acts, but the relationship between the dose given to the animal and the dose delivered to the different organs and tissues in the body. Studies in whole animals are required to ensure the proper use of beneficial chemicals such as medicines, because the tissue or organ receiving the beneficial effect might be harmed if exposures are greater than needed. In many cases, laboratory tools simply cannot duplicate these complicated phenomena. Ultimately, animal testing is the best method to detect effects such as cancer and birth defects.
Given the Above, What Is the Responsibility of the Toxicologist?
Scientists use whole living systems—animal models—in experiments to understand the relationships between exposure and effect, and to use them appropriately, responsibly and humanely. Data from these studies provide the essential foundation to distinguish and recommend which level of exposure is safe and which is harmful to people, animals and the environment.
What Are the Specific Benefits of Using Animals in Toxicology Research?
Safe Products and Safe Medicines—Toxicology studies are crucial to the discovery and development of safe products such as new drugs, cleaning products, plastic food containers, flame-retardant infant clothing and food additives, to name a few. Toxicologists perform research in whole animals to ensure the short-term and long-term safety of such products before they
are brought to market. If research on a new substance predicts significant risks to human or animal health, or to the environment, then that substance may never reach the marketplace. Alternatively, animal safety studies in combination with relevant information in humans can demonstrate that lower
doses of some medicines may produce the same beneficial effects with a reduction in side effects. Products previously available only by prescription can then be released. Recent examples include medicines used to treat inflammation and stomach ulcers. We all benefit from their increased availability and lower price as well as their pharmacologic properties. Animals also benefit from medicines originally developed for human use. In addition, research leads to useful safety and first aid label statements. These labels provide consumers with information to make wise choices about appropriate use. Toxicologists, using animal studies to validate results, provide a critical level of protection while enabling the use of products for an enhanced quality of life.
Avoiding Too Much of a Good Thing—All chemicals may cause harm, depending on the dose of the exposure. Toxicologists help determine the appropriate level of exposure, develop the understanding of how chemicals cause injury and, in addition, their studies provide treatment
alternatives in the event of poisoning. Information gained from research with animals is used by Poison Centers worldwide, where the majority of calls concern children under the age of five. How does a caregiver know what to do when a child drinks a household cleaner? The caregiver can call the Poison Center to learn the best action to take, based upon information from scientific studies conducted by toxicologists.
Safe Environment—Both animal and non-animal research is used to study the potential health problems associated with the world around us, including exposures to industrial processes, air pollution, soil and water contamination, hazardous waste and natural toxins. Toxicologists use these studies to determine how much of a substance is safe and how much might be hazardous. Use of lead in paints and gasoline resulted in high exposure to lead in homes and along highways. Studies with mice, for example, have demonstrated that even small amounts of lead can affect the nervous system and behavior. These effects were only evident in humans by subsequently conducting long-term studies that measured exposure in very large numbers of people. Then the importance of reducing lead exposure was clear.
Research is also necessary to reduce risk for workers who might be exposed to hazardous levels of a material in the workplace day in and day out. Animal studies can test for risk before human are exposed to dangerous situations, or help establish which mechanisms result in damage when consequences in humans are suspected. The results of these toxicity screens can be used to restrict or eliminate occupational contact with chemicals and thus protect the health of workers. For example, research in the fast-moving semiconductor industry identifies many novel chemicals, including unusual metal compounds created for their reactive properties. Animal studies are necessary in order to make informed decisions about worker protection on the production line where these compounds would be used.
In the regulatory world, the results of whole animal testing are often used to disallow or tightly regulate the amount of chemical released from facilities that treat, store or dispose of hazardous waste. Decisions must also be made about environmental remediation of possible contaminants. Human risk and hazard criteria for what constitutes a safe level of exposure to a possible environmental hazard are derived from in vitro and animal studies. Toxicologists establish the relationship between exposures received
by animals and those received by humans in order to interpret test results and predict risk. This in turn helps regulatory agencies to prioritize funding for environmental clean up.
Accurate assessment of risk from environmental exposure is difficult from laboratory models alone. Such experiments control and simplify variables. For example, in the laboratory a known dose of chemical may be administered to test animals in a liquid solution. This favors maximal absorption of the chemical. However, data from an experiment conducted in this manner may not accurately reflect how the chemical is absorbed into the body from contaminated soil. The impact of soil on the rate of absorption might be predicted from models that mimic conditions in the digestive system, but these models must be based on results obtained from living organisms. The matter is further complicated because some chemicals (such as arsenic) exist
in multiple forms in the environment. Testing absorption rates independently for each form of arsenic would only produce part of the picture. Mathematical and computer models based on the predicted relationship must be validated by tests in animals and humans.
The whole animal model, using species such as rats and miniature swine, is essential to equitably allocate limited resources to environmental remediation, just as in other decisions about human health and environmental protection.
Basic Research—Toxicology research often leads to breakthroughs in our understanding of disease and its treatment as well as in the development of new therapeutics. By studying how chemicals interact with living systems, toxicologists and other scientists unravel some of the fascinating mysteries of how living organisms normally function. For example, in the study of cancer-causing products created by ordinary combustion, such as barbecuing meat or burning plastics, toxicology research has shown that some of these (certain polynuclear aromatic hydrocarbons and chlorinated dioxins) will
combine with proteins called aryl hydrocarbon receptors that are found inside our cells. This combination can move into the cell nucleus, attach to DNA and influence the behavior of DNA and expression of genes. Further basic research in this area has shown that these protein receptors play an essential role in the normal development of mammalian cells. Therefore, research in toxicology has led to a better understanding of normal gene function.
The relationship of plants, animals and humans to the environment is a dynamic one, with normal physiological processes that allow living systems to process chemicals in constant balance with the world. Too little is known about many of these fundamental processes. The effects of disturbing this balance, for example by increasing levels of one substance, go largely unknown until some nonspecific, visible measure of toxicity becomes apparent. When predatory bird populations began decreasing in the early 1970’s, the source of the problem was not obvious. Ultimately scientists discovered that hatching failure was due to thinning of eggshells, which turned out to be a consequence of concentration of DDT in organisms high on the food chain. DDT interfered with eggshell production.
The use of animal models allows toxicologists to develop fundamental knowledge necessary to the understanding of chemical toxicity. This understanding can be translated into protection of humans, animals, and the environment from toxic levels of natural—as well as man-made—exposures.
[Necessity of Animal Research]
[Reliability of Animal Data]
[Commitment
to ResponsibleTreatment] [Advancing Valid Alternatives]
[Position Statement]
[Guiding
Principles] [Further Information] [Selected
References]
[Public Policy Statement] [Download
Printable Brochure]
In
the absence of human data, research with experimental animals is the most
reliable means of detecting important toxic properties of chemical substances
and for estimating risks to human and environmental health.
SOT
Animals in Research Public Policy Statement
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