That Reduce or Replace the Use of Animals
following is a brief overview of some new test methods available for use in the
high production volume (HPV) program to reduce or eliminate animal use:
Mammalian acute toxicity can be studied using cell culture (in vitro) systems because the actions of
toxic chemicals are often focused at the cellular level. For example, a series
of four cell culture tests can predict toxicity in humans with nearly 85
percent accuracy (compared to 65 percent in acute toxicity studies using
Fish acute toxicity is intended to
predict the potential for economic loss and ecological damage resulting from
fish death on a large scale. If exposure to test substances is toxic to the
food on which fish subsist, fish populations could be affected even without
direct fish toxicity. It is therefore reasonable to characterize the toxicity
of test substances to aquatic plants and invertebrates prior to consideration
of acute toxicity testing on fish. In addition, fish are often not the most
sensitive species, so in cases where fish acute toxicity is required, a single fish test can be
performed based on information from algae and shrimp.
In addition, fish
acute toxicity can be studied using computerized
(in silico) test methods such as ecological
structure-activity relationships (ECOSAR), rather than in vivo testing, which kills approximately 60 animals for each
test. In fact, no endpoint is better suited to the use of quantitative structure-activity
relationships (QSAR) tools than aquatic toxicity. (See the description of structure-activity
relationships below.) Even the Environmental Protection Agency (EPA) noted that if a QSAR
model is available, it may be used with the appropriate rationale for its
applicability to the HPV candidate chemical and identifies ECOSAR (a QSAR
program) as an available model to estimate aquatic ecotoxicity.
Repeated dose toxicity can be studied using cells cultured
from different body tissues to estimate the effects of a chemical on different
organ systems. For example, human liver cells in culture could be exposed to repeated,
low doses of a chemical in order to study how it is broken down (metabolized)
by the body and to identify any toxic by-products (metabolites) that may be
produced in the process. Stable human cell cultures have been produced for
kidney, nervous, immune, reproductive, and other essential organ systems. A
tiered testing strategy that combines several of these tissues in culture with
the use of computer and mathematical modeling has the potential to do away with
animal use in repeated-dose toxicity studies.
Reproductive toxicity and aspects of male and female
reproductive function can be modeled to some extent in vitro, and several cellular components of reproductive organs
can be maintained in cell culture. Although no test method has yet been used or
validated for routine use in reproductive toxicity studies, it is possible that
a battery of such systems may in the future be able to model a large proportion
of the male and female reproductive cycles, thereby reducing or replacing
animal use in reproductive toxicity testing.
Developmental toxicity can be studied in cell culture using an
embryonic stem cell test, which has been validated by the European
Centre for the Validation of Alternative Methods as a test for embryotoxicity—a
critical parameter and manifestation of developmental toxicity. This validated
test method is ideally suited for immediate use as a reduction measure in a
basic, screening-level program such as the EPA's HPV Challenge. Chemicals that
test positive for embryotoxicity could be classified as probable developmental
toxicants without further testing.
Genetic toxicity can be studied entirely without the use of
animals. Three methods in particular (the bacterial reverse mutation test, the
in vitro cell gene mutation test, and the in vitro chromosomal aberration test)
have been accepted by government regulators worldwide as valid alternatives to
using animals. Combined with information on metabolism, in vitro methods could replace the need for in vivo testing all together.
More generally, the following computer-based modeling approaches have
shown great promise in contributing to the replacement of animals in toxicity
Structure-activity relationship (SAR) analyses use computers
to seek to predict adverse biological effects of chemicals based on their molecular
structure, weight, and electronic charge. SAR data can be used to estimate
whether a specific chemical produces a particular biological response,
including toxicity, without recourse to animals. Such approaches have shown 85
to 97 percent accuracy in predicting dermal sensitization, teratogenicity, and
carcinogenicity for related groups of chemicals.
Computer-based mathematical modeling involves the use of
computers to model living biological systems, such as the human circulatory and
respiratory systems. For example, physiologically based bio-kinetic models
(PBBKs) use computers to study the absorption, distribution, metabolism, and
excretion of a chemical by the body. They can also be used to determine the
relationship between the dose of a chemical and a particular metabolic effect.
One such model, the ED01, studies tumor production in response to chemical
exposure. It can detect an increased tumor activity of 1 percent, and at doses
of a chemical much lower than those customarily used in rodent studies.
here to read more about the HPV chemical-testing program.
Almost all of us grew up eating meat, wearing leather, and going to circuses and zoos. We never considered the impact of these actions on the animals involved. For whatever reason, you are now asking the question: Why should animals have rights? Read more.