Reliability of Animal Data 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.
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.
Many complex interactions with a chemical can occur that
can only be detected in a living organism.
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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