Animals 24-7
April 2016
Testing device uses cells instead of animals
WASHINGTON D.C.––Can a robot detect substance toxicity toward humans faster and more accurately than a traditional test on rats, mice, fish, or other animals?
The Tox21 robot. (EPA photo)
Lab rabbit. (PETA photo)
The developers of the Tox21 robot, whose name is short for “Toxicology in
the 21st Century,” are betting that the robot can outperform traditional
tests––and betting, as well, that the robot can take the gamble out of
toxicity testing that results from the differences in how humans and animal
models digest and absorb chemical substances.
Developed by the toxicology establishment
For additional twist, the Tox21 robot developers are not animal advocates or
other outsiders from the regulatory process, trying to overturn the
biomedical research and safety testing establishment.
Rather, the Tox21 robot has emerged from the establishment, from an
eight-year collaboration among the four U.S. government agencies most
involved in toxicology research: the Environmental Protection Agency, the
National Toxicology Program, the National Institute of Environmental Health
Sciences, and the Food & Drug Administration.
10,000 chemicals
Explains the Tox21 web site, “Using a high-throughput robotic screening
system housed at the National Center for Advancing Translational Sciences,
researchers are testing a collection of 10,000 environmental chemicals and
approved drugs, called the Tox21 10K library, for their potential to disrupt
biological pathways that may result in toxicity. The team prioritizes
promising compounds identified from primary screening for further in-depth
investigation.”
Lab fish. (McMurry University photo)
Translation: there are only so many ways that chemicals can enter the human body and interact with it in ways that can cause harm. Tox21 looks at the points of entry for hints of vulnerability to each chemical being tested. Only if there are signs of vulnerability is the chemical flagged for more comprehensive testing, which may involve animal testing, or may not, depending on what sort of symptoms might be indicated.
Potential mitochondrial toxicants, as identified by a Tox21 screening
process. (NIH photo)
Cell-based assays
Elaborated Anna Azvolinsky in the January 26, 2016 edition of The Scientist,
describing data published the same day in the peer-reviewed journal Nature
Communications, “To reduce harm to animals and decrease the cost and time it
takes to generate animal-safety data, Ruili Huang, an informatics group
leader at NCATS, and her colleagues screened 10,000 chemicals through 30
different automated cell-based assays,” meaning a type of test that
determines the biologically active characteristics of each chemical.
All of the chemicals were of special interest to the EPA, National
Toxicology Program, or the National Institutes of Health.
Endocrine signaling
“Each assay,” Azvolinsky wrote, “assesses the ability of the chemicals to
interact with either a nuclear receptor pathway or a cellular stress
response pathway, including mitochondrial signaling pathways. The nuclear
receptor assays include testing environmental chemicals for their abilities
to disrupt endocrine signaling, which can result in harmful effects on
development, reproduction, and neurological functions.”
The Nature Communications study, Azvolinsky said, “demonstrates an ability
to test environmental chemicals found in drugs, food and food packaging,
consumer products, and chemicals produced during manufacturing and
industrial processes, using cell-based assays,” instead of live animals.
“Very efficient”
“The system is very efficient,” Huang told Azvolinsky. “We can test all the
chemicals at 15 different concentrations each and in three independent
experiment runs in one week. With animal testing, this would take years.”
But the Tox21 robot is not quite ready to take over toxicity testing
entirely.
“We can partly predict animal and human toxicity data,” Huang said, “but the
information is not perfect. We still need to add chemical structure data to
achieve a more accurate prediction,” explained Huang.
Still developmental work to do
Added British government toxicologist Fiona Sewell, “The [Tox21] data has so
far been more predictive of human rather than animal toxicity,” which
remains a concern of regulators.
Even in application to humans, Sewell cautioned, “This [study] is a positive
first step, but there is still a long way to go before we reach the ultimate
goal of being able to assess the safety of chemicals to humans without using
animals.”
During the next several years the Tox21 10k library is to be expanded to
cover data on about 80,000 chemicals, and to include a variety of additional
assays.
Shift from in vivo to in vitro
The Tox21 program began in 2008, recounted BioCentury staff writer Mark
Zipkin, “not only to reduce unnecessary use of animals, but to find better
and faster ways of predicting which chemicals and drug development
candidates might be toxic, because animal results translate so poorly to
humans.
“We propose a shift from primarily in vivo animal studies to in vitro
assays, in vivo assays with lower organisms, and computational modeling for
toxicity assessments,” jointly explained then-National Humane Genome
Research Institute director Francis S. Collins, EPA research and development
director George M. Gray, and National Toxicology Program associate director
John R. Bucher.
Following P&G path
Procter & Gamble, the largest U.S. consumer chemical maker, had already
pursued similar approaches for nearly a quarter century, in fulfilling a
1984 agreement P&G had reached with the late Henry Spira. founder of Animal
Rights International. Since then P&G has spent more than $350 million to
develop and win regulatory approval for more than 50 alternatives to animal
tests.
The Tox21 robot evolved from a high throughput test that National Institutes
of Health Chemical Genomics Center director Christopher Austin early in the
program described to Elizabeth Weise of USA Today as being “done in a
3-by-5-inch glass tray with 1,536 tiny wells, each a fraction of a
millimeter across. A few hundred human cells grown in a test tube go into
each well,” Weise wrote. “The testing machine drips a different chemical
into each well. After some time has passed, the machine shines a laser
through each well to see how many cells remain. A computer analyzes the
toxicity of each compound based on how the cells react.”
USGS Photo
Only 2,500 substances tested in 30 years
National Institutes of Health director Elias Zernouni indicated to Weise
that this relatively quick and simple test might replace animal-based
methods which as of 2008 had rigorously tested only about 2,500 potentially
toxic compounds in 30 years.
National Institutes of Environmental Health Sciences head Samuel Wilson told
Reuters that automated laboratories could, at the time, already use
non-animal methods to test 100,000 compounds at up to 15 different
concentrations in only two days.
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