09 Sep 2013: Report

How Tiny Fish Could Reveal
Effects of Chemical Exposure

Researchers at a lab at Oregon State University are using zebrafish to assess the impacts of multiple chemical exposures. Their findings could help lead to a better understanding of how chemicals in the environment and in consumer products affect human health.

by elizabeth grossman

Inside Oregon State University’s Sinnhuber Aquatic Research Laboratory are rooms lined with tanks filled with thousands of zebrafish — silver, striped, one- to two-inch creatures often found in home aquariums. The lab is the domain of Robert Tanguay, professor of molecular toxicology at Oregon State, whose zebrafish are helping to answer one of the most pressing questions in environmental health and toxicology: What are the health effects of chemical mixtures?

Tanguay has pioneered the use of zebrafish in toxicology. His lab is on the leading edge of this research, designing new experimental techniques and equipment that are enabling scientists to assess the impacts of multiple chemical exposures. Using zebrafish, Tanguay and other scientists are zeroing in on why certain chemical components of crude oil spilled by the Exxon Valdez in 1989 continue to adversely affect fish survival in Alaska’s Prince William Sound. With zebrafish, they also are learning why pesticide runoff can impair Pacific Northwest salmon’s ability to navigate, and how
The lab is evaluating the toxicity of thousands of chemicals used in consumer products.
oil from the ruptured Deepwater Horizon well is affecting marine species’ health in the Gulf of Mexico.

But zebrafish research goes well beyond the impact of chemical exposures on marine life. Zebrafish studies are also being used to assess the potential human health impacts of the chemical stew in U.S. Superfund sites. Tanguay’s lab is conducting research for the U.S. Environmental Protection Agency (EPA), evaluating the toxicity of thousands of chemicals used in countless consumer products. Zebrafish are also proving key to advancing our understanding of how particular chemical compounds affect the expression of individual genes that maintain and influence virtually every body system.

“Some people are still skeptical about how a fish can model human health,” said Tanguay during a tour of his lab earlier this month. “But during early development we are more similar to fish than at any other time in life.” Genes are particularly susceptible to environmental chemicals in early development. What happens then can set the stage for health throughout the rest of life.

The work of Tanguay and colleagues on mixtures is particularly important because, historically, chemicals have been evaluated and regulated one at a time. In reality, however, we are exposed to multiple chemicals daily throughout our lives. Because we now know that environmental chemical

View gallery
zebrafish in tank

Robert Tanguay
Tanks of thousands of zebrafish line the laboratory at Oregon State University.
exposure can profoundly influence the development of disease, understanding how mixtures may affect human health has taken on an urgency.

“We live in a chemical soup,” says Linda Birnbaum, director of the U.S. National Toxicology Program and the National Institutes of Environmental Health Science (NIEHS).

Zebrafish have been used since the 1990s for genetic modeling and screening, but it was Tanguay, while working as a post-doctoral fellow in 1995, who suggested they might be used in toxicology. Because they are vertebrates, these prolifically reproducing fish turn out to be an extremely useful model for understanding how cells in other vertebrates, including humans, respond to environmental chemicals. Zebrafish, which progress from a translucent egg to a recognizable baby fish in just 24 hours, are ideal for investigating how chemicals may affect biological processes at various stages of development.

Because zebrafish eggs develop outside the mother, they can be manipulated, and Tanguay’s lab has devised equipment and techniques for isolating the eggs to examine the effects of chemicals. In one lab, Tanguay showed me a petri dish containing translucent zebrafish eggs, no bigger than a poppy seed, and the thread-fine, glass needles used to extract genetic material. Tanguay’s researchers use that material to determine
What’s learned from these zebrafish can be used to inform human health research.
which base pair — a rung in the DNA double-helix ladder — is targeted by a particular chemical exposure.

The results of these perturbations will tell the scientists if the exposure prompts any physical or health abnormalities. The zebrafish genome has been sequenced, enabling scientists to identify genes associated with specific diseases. Because many zebrafish genes have human counterparts, what’s learned from these fish can be used to inform human health research.

By figuring out which chemical targets a specific genetic receptor, scientists can begin to connect chemical exposure to health effects. Zebrafish development is readily visible, enabling scientists to identify changes in a fish’s phenotype — its physical characteristics. The zebrafish’s rapid development and short generational cycle make it possible to pinpoint effects that could be difficult to see in other animals. After linking chemical and physical effects, scientists then work to connect the phenotype with the genetic mechanisms that prompt it — or, as Tanguay says, to “connect phenotype with genotype.”

Some of these changes may result in physical abnormalities. Zebrafish exposed to certain dioxins, for example, had deformed vertebrae and skulls. Dioxin exposure also impaired regeneration of wounded fins. Other changes may become apparent in neurological, cognitive, and behavioral testing. Still others may be exhibited as abnormalities in reproduction, altered developmental timing, or changes in how metabolism and other body systems function.

Zebrafish are instrumental in research to determine the effects of ‘cocktails of pollution’ on fish species.
Zebrafish are instrumental in the research that Nat Scholz, the ecotoxicology program manager at the National Oceanic and Atmospheric Administration’s Northwest Fisheries Science Center, is conducting to investigate the effects of what he calls “cocktails of pollution” on different fish species, including Pacific Northwest salmon and herring. Among the combinations of chemicals he’s studying are those of various fuel oil compounds, particularly polycyclic aromatic hydrocarbons (PAHs) and pesticides.

Using zebrafish, Scholz and his colleagues have discovered that certain PAHs adversely impact cardiovascular development, leading to a heart failure syndrome that can be lethal to fish larvae and reduce adult fish survival. The work with zebrafish has enabled the scientists to discover why fish that looked normal were dying. By examining how low levels of PAH exposure interfere with genes involved in heart development, they have begun to understand how oil from the Exxon Valdez and Deepwater Horizon spills has impaired the cardiovascular function of fish at a cellular level.

While the PAH exposure prompts changes early in development, these effects may not become apparent until later on, when defects — in how the heart processes potassium and calcium and in heart structure — reduce cardiac function and cause swimming problems. Experiments with zebrafish have helped deduce which enzymes and genetic receptors are affected by which hydrocarbon compounds, something that’s not been possible with fish in the wild.

Tanguay’s lab is also working with the EPA and NIEHS on an ongoing project known as Tox21, which is assessing more than 10,000 commercially produced chemicals for a wide number of health effects. Zebrafish are being used as part of what is called “high-throughput” screening — the rapid testing of lots of chemicals. The goal is to fill the many gaps in toxicity data that exist for these chemicals and identify which chemical compositions or concentrations prompt specific health effects. Results of this screening are expected later this year.

“We call this Robot Row,” said Tanguay, showing me the lab area devoted to robotic machines designed to precisely dose hundreds of zebrafish eggs and genetic material samples. Because zebrafish develop so quickly, lots of variables can be examined concurrently using these machines. Tanguay’s lab uses what look like tiny paint palettes with an array of 96 little wells,
The lab is working to assess the toxicity of molecules invented to clean up environmental contaminants.
each of which gets a zebrafish sample that is then dosed by a machine with a particular chemical at different concentrations. Some experimentally treated eggs are allowed to develop, while others are halted to examine impacts during embryonic development.

Tanguay is also working with Terry Collins, professor of chemistry and director of Carnegie Mellon University’s Institute for Green Science, to assess the toxicity of molecules Collins has invented to clean up environmental contaminants. These compounds, known as TAML activators, can be used to remove dyes and other toxic chemicals from water. The TAML compounds appear to be successful in degrading these hazardous chemicals, but Collins wants to make sure their use doesn’t produce other harmful compounds or effects. Collins’ and Tanguay’s labs have been testing TAML activators on zebrafish to determine any potential toxicity, including on endocrine hormones.

The scientists are examining a complex range of possible outcomes that may result from the chemicals’ interaction with specific genetic receptors at different stages of development. If no abnormal effects are seen after the various TAML exposures, Collins will be closer to determining the safety of his chemical products. If adverse effects are seen, he will have the information he needs to begin redesigning his compounds so they are safe to use.

View gallery
zebrafish embryos

Robert Tanguay
Zebrafish embryos develop from eggs to recognizable baby fish in 24 hours.

Tanguay’s lab has also designed equipment to test cognitive and behavioral responses in zebrafish. Similar to tests used with other lab animals, including humans, these experiments reveal how the brain, nervous system, and muscles may be affected by certain chemicals, such as organophosphate pesticides, known neurotoxicants that have been linked to adverse neurological effects in children. By using zebrafish, scientists have begun to locate which neurons these chemicals may affect at particular stages of development. These experiments are also being used to test the effects on fish of pesticide-laden water running off fields and roads.

The ultimate goal is to learn which chemical combinations, concentrations, and structures alter the normal function of genes and hormones. There is strong evidence, for example, that interference with endocrine system hormones and the genes that regulate them can lead to metabolic disorders such as diabetes and obesity. Research has also shown that endocrine-disrupting chemicals can upset reproductive, developmental, immune system, and neurological health. In addition, scientists have discovered that altered gene expression — distinctly different from genetic mutation — can be passed from one generation to another in what are called epigenetic effects. Pinpointing these precursors to disease is key to protecting and improving human health.

The ability to connect specific chemicals in the environment with mechanisms of disease is essential to finding and “eliminating those that are nasty,” explains Tanguay. In a world where manufactured chemicals are ubiquitous, the tiny, fecund zebrafish is playing a big role in discovering how this chemical stew is affecting our health.

POSTED ON 09 Sep 2013 IN Business & Innovation Energy Policy & Politics Pollution & Health Science & Technology Asia North America 

COMMENTS


It's about time that we start studying subtoxic combinations of thousands of chemicals. Scientists are loathe to do such experiments because of the difficulty of interpreting results, but I have always suspected there are big surprises that have been missed due to our insistence that all experiments be designed so that results can be teased apart.

What if 1,000 common chemicals are each combined at 1/10,000 of their LD50 (or some more sophisticated level) — what would be the result? I hope that these researchers at least try a few "hopelessly complex" mixtures. Perhaps that is in effect what the testing of water runoff from Superfund sites is doing?
Posted by Roger W Faulkner on 09 Sep 2013


I wonder if these results will be available and appropriate for reference with GHS hazardous material classification, now required under OSHA hazard communication. Ecotox is exempt under OSHA, but other countries require it, and possibly EPA will too.
Posted by Casey Wallace on 16 Sep 2013


I think that it is refreshing to see that someone is finally doing something about trying to uncover the hidden effects of the numerous harmful chemicals we are constantly pumping into our environment. Why should we be poisoning ourselves and the generations to come? Every artificial thing that we introduce to the environment does not belong there, so why are we continuously poisoning our home and food? It makes no sense to me.
Posted by Molly Graham on 17 Sep 2013


It's very interesting to see how the effects of multiple chemical exposures at different parts of a life cycle are being studied, rather than only focusing on one chemical or stage of development. However, studying these effects on the zebra fish can only provide so much information, and while we can't study these effects on humans, it wouldn't be a bad idea to try testing other fish and animals in the same way to see what results they give.
Posted by Tom Flynn on 17 Sep 2013


This is an interesting topic, and I am glad to see someone is taking an interest in finding out what the chemicals we are subjected to everyday really can do to us. I am curious if the science, and potential effects from chemicals, are still valid after the test subject passes the early stages of development? Can this information still be applied to humans even after the fish has passed early developmental stages?
Posted by Kelly Beall on 18 Sep 2013


This is a great stepping stone in determining just how dangerous our everyday use chemicals are. Studies like these show the urgent need to adopt the precautionary principle in relation to chemical releases into the manufacturing market.
Posted by DLR on 19 Sep 2013


This is an interesting article, and I think that it's great that they are learning the possible outcomes of chemical exposure through zebrafish. Which ultimately can help see the impacts that these chemicals can have on human health. Also the information regarding gene expression changes in early life is fascinating and invaluable.
Posted by Mahmoud A on 06 Oct 2013


POST A COMMENT

Comments are moderated and will be reviewed before they are posted to ensure they are on topic, relevant, and not abusive. They may be edited for length and clarity. By filling out this form, you give Yale Environment 360 permission to publish this comment.

Name 
Email address 
Comment 
 
Please type the text shown in the graphic.


elizabeth grossmanABOUT THE AUTHOR
Elizabeth Grossman is the author of Chasing Molecules: Poisonous Products, Human Health, and other books. Her work has appeared in Scientific American, Salon, The Washington Post, The Nation, Mother Jones, Grist, and other publications. In earlier articles for Yale e360, she reported on recent studies suggesting a possible link between prenatal exposure to pesticides and the mental abilities of children and explored how declining bee populations threaten global food security.
MORE BY THIS AUTHOR

 
 

RELATED ARTICLES


On Ravaged Tar Sands Lands,
Big Challenges for Reclamation

The mining of Canada’s tar sands has destroyed large areas of sensitive wetlands in Alberta. Oil sands companies have vowed to reclaim this land, but little restoration has occurred so far and many scientists say it is virtually impossible to rebuild these complex ecosystems.
READ MORE

As Fracking Booms, Growing
Concerns About Wastewater

With hydraulic fracturing for oil and gas continuing to proliferate across the U.S., scientists and environmental activists are raising questions about whether millions of gallons of contaminated drilling fluids could be threatening water supplies and human health.
READ MORE

In Developing World, A Push to
Bring E-Waste Out of Shadows

For decades, hazardous electronic waste from around the world has been processed in unsafe backyard recycling operations in Asia and Africa. Now, a small but growing movement is seeking to provide these informal collectors with incentives to sell e-waste to advanced recycling facilities.
READ MORE

As Uses of Biochar Expand,
Climate Benefits Still Uncertain

Research shows that biochar made from plant fodder and even chicken manure can be used to scrub mercury from power plant emissions and clean up polluted soil. The big question is whether biochar can be produced on a sufficiently large scale to slow or reverse global warming.
READ MORE

A Legal Call to Arms to Remedy
Environmental and Climate Ills

University of Oregon law professor Mary Wood says environmental laws in the United States are simply not working. In an interview with Yale Environment 360, she explains why she believes a new strategy and robust judicial intervention are needed to protect nature and the climate.
READ MORE

 

MORE IN Reports


Unsustainable Seafood: A New
Crackdown on Illegal Fishing

by richard conniff
A recent study shows that a surprisingly large amount of the seafood sold in U.S. markets is caught illegally. In a series of actions over the last few months, governments and international regulators have started taking aim at stopping this illicit trade in contraband fish.
READ MORE

A Public Relations Drive to
Stop Illegal Rhino Horn Trade

by mike ives
Conservation groups are mounting campaigns to persuade Vietnamese consumers that buying rhino horn is decidedly uncool. But such efforts are likely to succeed only as part of a broader initiative to crack down on an illicit trade that is decimating African rhino populations.
READ MORE

On Fracking Front, A Push
To Reduce Leaks of Methane

by roger real drouin
Scientists, engineers, and government regulators are increasingly turning their attention to solving one of the chief environmental problems associated with fracking for natural gas and oil – significant leaks of methane, a potent greenhouse gas.
READ MORE

Scientists Focus on Polar Waters
As Threat of Acidification Grows

by jo chandler
A sophisticated and challenging experiment in Antarctica is the latest effort to study ocean acidification in the polar regions, where frigid waters are expected to feel most acutely the ecological impacts of acidic conditions not seen in millions of years.
READ MORE

On Ravaged Tar Sands Lands,
Big Challenges for Reclamation

by ed struzik
The mining of Canada’s tar sands has destroyed large areas of sensitive wetlands in Alberta. Oil sands companies have vowed to reclaim this land, but little restoration has occurred so far and many scientists say it is virtually impossible to rebuild these complex ecosystems.
READ MORE

A New Leaf in the Rainforest:
Longtime Villain Vows Reform

by rhett butler
Few companies have done as much damage to the world’s tropical forests as Asia Pulp & Paper. But under intense pressure from its customers and conservation groups, APP has embarked on a series of changes that could significantly reduce deforestation in Indonesia and serve as a model for forestry reform.
READ MORE

In a Host of Small Sources,
Scientists See Energy Windfall

by cheryl katz
The emerging field of “energy scavenging” is drawing on a wide array of untapped energy sources­ — including radio waves, vibrations created by moving objects, and waste heat from computers or car exhaust systems — to generate electricity and boost efficiency.
READ MORE

Life on Mekong Faces Threats
As Major Dams Begin to Rise

by joshua zaffos
With a massive dam under construction in Laos and other dams on the way, the Mekong River is facing a wave of hydroelectric projects that could profoundly alter the river’s ecology and disrupt the food supplies of millions of people in Southeast Asia.
READ MORE

As Fracking Booms, Growing
Concerns About Wastewater

by roger real drouin
With hydraulic fracturing for oil and gas continuing to proliferate across the U.S., scientists and environmental activists are raising questions about whether millions of gallons of contaminated drilling fluids could be threatening water supplies and human health.
READ MORE

In Developing World, A Push to
Bring E-Waste Out of Shadows

by mike ives
For decades, hazardous electronic waste from around the world has been processed in unsafe backyard recycling operations in Asia and Africa. Now, a small but growing movement is seeking to provide these informal collectors with incentives to sell e-waste to advanced recycling facilities.
READ MORE


e360 digest
Yale
Yale Environment 360 is
a publication of the
Yale School of Forestry
& Environmental Studies
.

SEARCH e360



Donate to Yale Environment 360
Yale Environment 360 Newsletter

CONNECT

Twitter: YaleE360
e360 on Facebook
Donate to e360
View mobile site
Bookmark
Share e360
Subscribe to our newsletter
Subscribe to our feed:
rss


ABOUT

About e360
Contact
Submission Guidelines
Reprints

e360 video contest
Yale Environment 360 is sponsoring a contest to honor the best environmental videos.
Find more contest information.


DEPARTMENTS

Opinion
Reports
Analysis
Interviews
Forums
e360 Digest
Podcasts
Video Reports

TOPICS

Biodiversity
Business & Innovation
Climate
Energy
Forests
Oceans
Policy & Politics
Pollution & Health
Science & Technology
Sustainability
Urbanization
Water

REGIONS

Antarctica and the Arctic
Africa
Asia
Australia
Central & South America
Europe
Middle East
North America

E360 en Español

Universia partnership
Yale Environment 360 articles are now available in Spanish and Portuguese on Universia, the online educational network.
Visit the site.

e360 MOBILE

Mobile
The latest
from Yale
Environment 360
is now available for mobile devices at e360.yale.edu/mobile.

e360 VIDEO

Warriors of Qiugang
The Warriors of Qiugang, a Yale Environment 360 video that chronicles the story of a Chinese village’s fight against a polluting chemical plant, was nominated for a 2011 Academy Award for Best Documentary (Short Subject). Watch the video.


header image
Top Image: aerial view of Iceland. © Google & TerraMetrics.

e360 VIDEO

Colorado River Video
In a Yale Environment 360 video, photographer Pete McBride documents how increasing water demands have transformed the Colorado River, the lifeblood of the arid Southwest. Watch the video.

 

OF INTEREST



Yale