Canadian researchers leading development of better, faster, less costly ways to test safety of chemicals

Developing and enforcing regulations to protect the health and safety of citizens is one of the most fundamental responsibilities of government. We may not think about them very often, but regulations help to ensure that everything from the medicines we take to the foods we eat and even the air we breathe are as safe as possible.

All of those things, and many more, contain chemicals. It is the job of regulatory toxicologists to study those chemicals, and recommend to government whether our exposure to them should be limited by regulation. For many chemicals, the damage they can do may not be apparent for many years — chemicals that can cause cancer, for example.

An inexact science

Traditional methods of testing for these kinds of chemical toxicities have been in use for decades. Basically, they involve exposing laboratory animals to a chemical, and studying the animals to see how it affects them. To be on the safe side, the animals are usually exposed to much higher levels of a chemical than would ever be likely to happen in everyday life. It is an expensive and slow process and, in a sense, a somewhat inexact science.

At Health Canada, a team of research scientists led by Dr. Carole Yauk is studying how genomics can provide a faster, less expensive and more accurate way to determine the toxicity of chemicals we may be exposed to in our daily lives.

"Existing toxicity testing can tell us what a chemical does," says Dr. Yauk, "But it doesn't really give us much information about the mechanics of its toxicity — we can't see how it is causing the damage."

New understanding, new precision

Genomics is changing that, opening the relatively new field of toxicogenomics. As Dr. Yauk explains, "Everything is getting smaller and smaller. Today, we can see functions of a cell that we'd never been able to see before, and we can see how cells respond to the different stresses that exposure to chemicals can cause."

Working with chemicals that are known to be toxic, the Health Canada researchers are developing genomics-based testing methods that will allow, among other benefits, for much more accurate ways to judge the level at which exposure to a particular chemical poses a danger.

Today, for example, one of the first tests for a chemical or drug is seeing how it affects human cells in a test tube. If the drug causes breaks in the DNA of the cells — a strong indication that it can cause cancer — alarm bells are raised and appropriate follow-up tests are called for. The big drawback to that method is that this kind of positive response in a cell culture in a test tube does not necessarily mean the same positive response will happen in a living animal — in part because the doses used in the testing are far higher than anything that would happen in the real world.

"With the test method we are developing, we are able to see the impact of various dosages of a chemical with much greater accuracy," says Dr. Yauk. "In addition, we can study the biology underlying how the chemical causes harm in order to understand how relevant this would be in human tissues at the doses they are likely to experience in real life."

Protecting Canadians

In the longer term, Dr. Yauk says the new tests will allow scientists to provide regulators with more and better information about the toxicity of chemicals at less cost and in less time, leading to better regulation and greater protection for the health and safety of Canadians.

While the research being conducted by Dr. Yauk and her team is still at a relatively early stage, it is already making a name for Canada in the global genomics community. Dr. Yauk has been invited to join the Organization for Economic Cooperation and Development (OECD) group that is developing international strategies for using toxicogenomics in regulatory policy. Dr. Yauk and her team also collaborate with experts around the world through the Washington-based International Life Sciences Institute.

Raising Canada's profile

As for the impact of the Government of Canada's Genomics Research and Development Initiative (GRDI) on her work, Dr. Yauk says, "We would never have been able to make this kind of progress or achieve this level of international credibility for Canada without the funding we've received through the GRDI. From enabling us to acquire the lab equipment and other infrastructure that allows us to do the work to leveraging funds from other sources to expand our research, GRDI has been absolutely fundamental."

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