Robot Allows High-Speed Testing of Chemicals
For the first time, toxic screening is underway for
thousands of chemicals in daily use
By David Biello
Scientific American
October 13, 2011
http://www.scientificamerican.com/article.cfm?id=robot-allows-high-speed-chemical-testing

Of the more than 80,000 chemicals used in the U.S., only
300 or so have ever undergone health and safety testing.
In fact, only five chemicals have ever been restricted
or banned by the U.S. Environmental Protection Agency
(EPA). But now some 10,000 agricultural and industrial
chemicals-as well as food additives-will be screened for
toxicity for the first time, with the help of a rapid-
fire testing robot.

"We are screening 10,000 chemicals using these rapid
tests to characterize the bioactivity of the chemicals
to predict their hazard and to use that information to
prioritize for further screening and testing," says
biologist David Dix, deputy director of EPA's National
Center for Computational Toxicology. "We can test a lot
of chemicals with a lot of repetitions at a lot of
different concentrations."

The program, initially started at EPA as ToxCast to
assess 1,000 chemicals (and known as Tox21 in its
expanded form), employs a robot to speed chemical
screening. On plastic plates filled with 1,536 tiny
wells, the robot drops varying amounts of different
chemicals onto human cells and human proteins.
Essentially, each plate has 1,536 experiments underway
at the same time. "In a stack of 100, we have 150,000
combinations of chemicals and targets," Dix says.

The robot arm and its numerous five- to 10-microliter
wells replace the old standby of toxicology-animal
testing. In addition to being slow and controversial,
animal tests do not reveal how a chemical might impact
humans, nor do they deliver any insight into the
mechanisms by which a given chemical produced toxic
outcomes. Simply by running the robotic tests, the EPA
and its partner agencies will generate more information
on chemical toxicity in the next few years than has been
created in the past century. The effort has already
screened more than 2,500 chemicals, including the
dispersants employed to clean up BP's 2010 oil spill in
the Gulf of Mexico.

The new information may allow toxicology to evolve from
a reactive science to a predictive one; models of liver
toxicity based on chemical testing, for example, could
predict how new chemicals would interact with the liver,
based on molecular structure and other information.
Already, ToxCast scientists have made such a predictive
model for liver toxicity: It forecast accurately tumor
formation in rats and mice that had been exposed for two
years to certain chemicals. A similar effort proved
accurate for reproductive toxicity, including vascular
development and endocrine disruption-an area of keen
interest for human exposure to chemicals such as
bisphenol A (BPA).

In addition, the high-speed robotic testing will allow
toxicologists to better understand mixture and low-dose
effects by testing both combinations of chemicals for
additive damage as well as how, for example, 15
different concentrations of a given chemical impact
human cells. "We suspect that when we look at 10,000
chemicals we'll see a lot of activity that we didn't
know about," Dix says of the two-year effort, in which
the EPA has partnered with a handful of federal health
agencies.

"For a lot of chemicals, there's no requirement for
animal toxicity testing or any other type of testing,"
Dix notes. "Tox21 is going to provide information where
there is no information."

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