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Topic 1.docx

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University of Waterloo
HLTH 340
Steve Mc Coll

Topic 1 Topic 1: Overview Exploring the Different Sides of Toxicology  Give the two definitions of toxicology, and explain why one of them is more accurate. o OK, so there is a "naïve" and a "more accurate" definition for toxicology  Naively, we would say that toxicology is the science of poisons  However, the more accurate definition is that environmental toxicology studies the potentially harmful AND beneficial effects of environmental chemicals on living organisms o This is because many poisonous substances have beneficial effects in small doses, and so they can be helpful to us if we incorporate them into our systems in a controlled manner  Example: Digoxin is a treatment for CHF that is actually a poison when it is taken too much  What is one exception to the above concept? o It should be noted that not all substances act like this -- some substances are so toxic that they are not beneficial at ANY level  Example: heavy metals such as mercury and lead  What implication does this tension have for policy making? Give an example. o This issue was present with DDT, where it was originally made because it was effective at killing mosquitoes and thus preventing them from damaging crops  However, it was quickly banned when it was discovered that DDT could build up in living organisms and cause reproductive failure  The tension developed when the WHO decided that the benefits were worth the risks in African countries, where mosquitoes not only destroy crops but also carry malaria  So now countries such as Canada have to consider this tension when developing policy, such as "Should we export DDT to African countries?" o So this exemplifies the tension - when we are making policies such as whether to ban substances, we need to be aware of many things:  The benefits of a substance versus its harmful effects  Whether the substitute solution is any better (some say that organophosphates, which replaced DDT, are even worse than DDT)  What are the effects of banning the substance (other than the fact that it will be no longer a risk)? (For example, the financial consequences)  How severe are the risks, really? (With the acrylamide example below, you would have to eat an unrealistic amount of fries to suffer from its harmful effects)  What is another application of toxicology (besides policy making)? Explain it. o Modern toxicology often studies the use of chemicals as probes (into a cell) to better understand molecular/cellular processes that affect health o The toxic substance goes into the cell and exerts its effect - by perturbing or changing some aspect of the cell's metabolism, and by observing the results we can learn more about these processes Exposure to Toxicants  Compare and contrast the two different kinds of exposures, and give examples. o There are unintentional exposures (COMMON) and intentional exposures (RARE) o Unintentional exposure are rampant throughout our environment, and so there are many examples:  Fish that have lots of omega-3 also have lots of mercury  Ephedra is also a big deal: it is a herb which is (was) frequently used (especially amongst natural health practitioners) for colds and flu  However, since it is a mild stimulant, if you are UNINTENTIONALLY exposed to excessive amounts of it, you can get heart arrythmias, strokes, and so on  California started issuing warnings for fries, because if the fries are over- heated then we get the toxicant known as acrylamide  Acrylamide is carcinogenic and also toxic to the nervous system o Intentional exposures require INTENT on the part of some human to put a lot of toxin into someone else, for example Victor Yushchenko (politician in the Ukraine)  A special form of Dioxin called TCDD was used to do this, and it was so purified that we were able to see what h725appened when someone ingests a LARGE amount of Dioxin  Result: he has chloroacne and severe liver damage Factors to Consider When Thinking About Toxicity/Toxicology  Explain why TIME is such an important factor to consider when we think about toxicology. o Well firstly, toxicology is arguably the oldest scientific discipline, as the earliest humans had to recognize which plants were safe to eat  One implication of this is that it is not just recently that toxicology has become a relevant issue on the public agenda: we may INCORRECTLY think that it is because of things like the Industrial Revolution - that is, it is MAN's fault that we have to worry about toxicology as a subject o Another reason why TIME is relevant is because over time, humans have been able to adapt biochemical defenses against all the toxic combustion products in the environment, such as wood smoke (which we did a LONG time before the Industrial Revolution)  One implication of this is how well our bodies can deal with toxic substances that we have NOT adapted defenses for - more specifically, ARTIFICIAL toxins (things made by us, and not the environment)  However, it remains true that MOST EXPOSURE of humans to chemicals is (still) via naturally occurring compounds consumed in the diet from food plants o Lastly, time is also important because none of us are toxicological virgins -- as soon as we were born , we were exposed to all sorts of trace chemicals in the environment -- some bad, some not so bad  And the POINT here is that these chemicals (can potentially) build up in our tissues over TIME (if they are persistent) and ultimately cause damage in the FUTURE: thus environmental health is a discipline not only concerned about the present, but also about the future -- they have to consider the deleterious potential of chemicals on a long-term scale  Notably, even if certain chemicals are not accumulative, short-lived substances can still do DNA damage and THAT damage can build up over time to give us stuff like cancer…or other genetic problems like birth defects  What is one important source of variation when we are thinking about the kind of damage which we may experience due to toxins?  HUMAN UNIQUENESS -- or more formally, genetic differences -- must be considered in toxicology  The thing about environmental health that makes things complicated is that there is biochemical individuality -- everyone has a different enzyme profile, so a toxic exposure that might not affect most people could affect a small number of people because they are less resistant than the general population  This uniqueness can result from:  Genetic inheritance  But also life experiences -- what we have been exposed to before, and have been able to build up resistance to How did we get here? (Toxicologically speaking)  Explain how the discipline of toxicology evolved, especially our MOTIVATION to learn about this area. o Firstly, this is the big picture: modern environmental toxicology developed from increased public awareness of environmental hazards (specifically, DDT) o Here is how that happened:  Firstly, we had a book named "Silent Spring" written (in 1960) by Rachel Carson in which she talked about her concerns for what synthetic pesticides were doing to the health of the ENVIRONMENT  More specifically, she was a wildlife biologist so she was concerned for the health of eagles, hawks, fish, etc.  She saw that the pesticides were negatively affecting the hormone balance in these animals so that they were losing reproductive capacity  From there, it was realized that toxicants which affected wildlife could ALSO AFFECT HUMANS  Thus by the mid 1970's, many new laws were put in place in countries like CAN and USA to more tightly control the production and release of pesticides and toxic heavy metals  So within a 10-year span, a lot of the worst sources of environmental pollution were put under control (note that it was only the worst ones -- more on this later)  Another issue that the field of toxicology had to work through is the idea of different degrees of toxicity. What are the problems/issues that arise when we think about how some toxicants are worse than others? What single factor worsens all these problems? o The idea is that it is harder to know what to do with the less extreme cases -- with the extreme ones it is easy…we just ban them! o However, with less toxic compounds it is going to be REGULATIONS (i.e. production limits for industrial factories) instead of bans -- and careful thinking has to be done to decide where these regulations will be set o Also the degree of toxicity of some compound can be tricky because it may fool us -- a chemical may appear safe, but actually be dangerous o The factor that multiplies our headaches is that there are so many chemicals being manufactured, and it is difficult to get through all of them  In fact, approximately 100,000 chemicals are currently in use worldwide, and 500 new chemicals enter the marketplace annually Different Areas within Toxicology  What are major areas of specialization in toxicology? o Mechanistic toxicology (basic biology and chemistry) o Descriptive toxicology (testing) o Regulatory toxicology (standard-setting and compliance) o Risk assessment (modeling) Mechanistic Toxicology  What are the major traits of mechanistic toxicology? o It focuses on "how" -- it is an explanatory discipline  How does a chemical produce an adverse health effect?  i.e. What is it about a benzene ring that allows it to enter a cell and do damage?  How does a biological system protect itself against a possible adverse health effect? o It involves certain other fields of science  Firstly, cellular and molecular biology are big players here  Chemistry is also heavily involved here, because it is often (obviously?) the chemical properties of some substance that allow it to do damage  What are 3 terms which are used to describe chemical compounds and how they relate to the body? o Xenobiotic compound: a chemical that is foreign to the organism  It is "foreign" to the body -- not naturally manufactured, nor is it taken in as a natural food substance o Byproduct/metabolite: a chemical produced by metabolic biotransformati
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