Module 6 - Environmental Toxicology and Cancer PDF

# Module 6 - Environmental Toxicology and Cancer ## 01 - Environmental Toxicants * **Environmental Toxicant** - a chemical that is released into the environment and that can produce adverse health effects on living organisms * **Acute Toxicity** - associated with a single exposure to a chemical (...

# Module 6 - Environmental Toxicology and Cancer ## 01 - Environmental Toxicants * **Environmental Toxicant** - a chemical that is released into the environment and that can produce adverse health effects on living organisms * **Acute Toxicity** - associated with a single exposure to a chemical (often a large dose) * ie. chemical spill * **Chronic Toxicity** - associated with repeated exposure to a small dose of a chemical over a long period of time * ie. eating contaminated food **Example: Aflatoxin B₁** * Common food contaminant * Acute toxicity can result in liver failure/death * Chronic toxicity can cause liver cancer ## Common Environmental Toxicants ### Air Pollution * Can be divided into two main categories: **Particulate Matter** and **Gaseous Air Pollutants** #### Particulate Matter * Refers to a mixture of tiny particles composed of non-gaseous pollutants (ie. biological materials) * Can be liquid droplets or solids #### Gaseous Air Pollutants * Carbon monoxide, carbon dioxide, nitrogen oxides, sulfur oxides, ozone, etc * Can be attributed to both natural and anthropogenic sources **Natural Air Pollutants** * Volcanoes, forest/prairie fires, and dust storms **Anthropogenic Air Pollutants** * Man-made * Combustion of fossil fuels for heating + power * Automobile exhaust releases smoke, lead particles, CO₂, and nitrogen oxides * Green vehicles have helped reduce this * Industrial processes release a wide variety of pollutants * Type of pollutant depends on the manufacturing process * The predominant health effects associated with air pollution is chemical irritation of the respiratory tract. * Health problems are usually due to the combined action of particulates and sulfur dioxides * But no single pollutant seems responsible * Certain subpopulations are susceptible to air pollution **Tobacco Smoke** * The combination of mainstream smoke and sidestream smoke * It has been suggested that exposure to environmental tobacco smoke carries the same health risks as directly smoking ## Pesticides * Unique because they are used to intentionally kill organisms * **Insecticides** and **herbicides** are the two major classes that act as environmental toxicants ### Insecticides * Chemicals used to kill insects or to make them unable to reproduce or develop normally #### Organochloride Insecticides * Work by increasing the sensitivity of neurons, resulting in increased CNS stimulation that manifests as tremors, convulsions, and death. * Residues in humans, animals, and the environment can present long-term problems that are not completely understood * Ex: DDT * Originally introduced in 1945 to control malaria-containing mosquitoes. * Very effective and used until the 1970s * Stopped being used bc: * Insects were developing resistance. * Bird + fish populations were decreasing. * Soil + water DDT conc were increasing. * DDT levels in food were increasing. #### Organophosphorus Insecticides * First synthesized in WWII as potential warfare agents (ie. nerve gas) * Selective ones have since been developed that require metabolic activation which occurs rapidly in insects * They are relatively unstable and break down in the environment. * So they are said to have an overall small impact on the environment. * They are very toxic to humans. * They are absorbed through the skin and are the number one cause of poisoning in agriculture. * They irreversibly inhibit acetylcholinesterase. * This causes acetylcholine to build up causing an increase in acetylcholine-mediated neural firing. * Results in decreased heart rate, severe difficulty breathing, fecal + urinary incontinence, and blurred vision. * Can result in death. ### Herbicides - chemicals capable of killing or injuring plants * Agent Orange ## No standards for permissible levels of pharmaceuticals in drinking water and food sources exist ## Concentration of Pharmaceuticals in the Environment * Depends on a number of factors: * Extent of use * Dose administered * Persistence in the environment * Ability of sewage treatment to remove the agent * The minimum therapeutic dose is used to determine the risk of various concentrations of pharmaceuticals in the environment to humans. * This fails for anticancer drugs because even at the minimal dose, significant toxicities occur. ## 03 - Cancer and Chemotherapeutics ### Cancer Statistics * Primarily affects Canadians 50 or older. * 45% of males and 43% of females will develop cancer at some point in their lives. * One in every 2.3 people * 30% of all deaths in Canada are due to cancer. * Lung cancer contributing to this the most ### Key Features of Cancer Cells * They have the ability to grow and divide indefinitely. * They have the ability to invade surrounding normal tissue. * They can spread throughout the body (metastasize). ### Causes of Cancer **Genetics** * An individual's genetic makeup contributes to a variation in response to carcinogens. * Ex: Individuals with Xeroderma pigmentosum have a genetically-based deficiency in DNA repair, leaving them more prone to mutations. **Environmental Factors** * Include environmental chemicals, diet, infections, etc. * These factors are modifiable meaning a person can decrease the risk of exposure. * **Tobacco Use** * Smoking causes many cancers: lung, esophageal, bladder, and pancreatic. * Development of cancer depends on the tar content of the cigarette smoked, the frequency of smoking, and the duration of the habit. * Smokers are eight times more likely to develop lung cancer than non-smokers. * Passive smoking is also a risk factor for cancer. * **Adult Diet** * Saturated animal fat and red meat are strongly linked to cancer of the colon, rectum, and prostate. * High intake of salt has been linked to stomach and other cancers. * Skimping on fresh fish and vegetables can contribute to many different types of cancer. * It is thought that fruits and vegetables contain constituents that block cancer-inducing chemicals produced in the body. * **Occupational Factors** * Occupational exposure to carcinogens are not that strictly controlled in developing countries. * Common carcinogenic hazards: * Asbestos - lung cancer * Benzene - leukemia * Formaldehyde - nose * Ionizing radiation - bone marrow * Soot - Skin * **Viruses and Infection** * Helicobacter pylor (the bacterium responsible for causing stomach ulcers) is strongly associated with stomach cancer. (80% are caused by them). * Hepatitis B and C can cause liver cancer. * HPV can cause cervical cancer. ### Cancer Prevention * Avoid excessive sunlight * Monitor alcohol intake * Eliminate tobacco use * Eat healthy * Be active * Get vaccinated ### Goals of Cancer Treatment * **Prevent the Cancer** * Given to prevent cancer cell growth or remove precancerous cells that could turn into cancer. * **Cure the Cancer** * This is the primary goal of treatment. * Cures have only been achieved for a few cancers. * **Control the Cancer** * Stop it from growing and spreading. * Prolonging patient survival. * When a cure isn't possible. * **Relieve Symptoms** * When curing or controlling the cancer is not possible. * Make the patient as comfortable as possible. * Can include medications for controlling symptoms. ### Treatment of Cancer * Main types of treatments include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. ## 02 - Pharmaceuticals in the Environment ### Adverse Effects of Pharmaceuticals in the Environment * The increased use of pharmaceuticals has resulted in the recognition of them as relevant environmental pollutants in surface water, ground water, and soils. * Surface water is the most studied & relevant as it relates to human health. * Includes: rivers, streams, and lakes. * The concs of pharmaceuticals found in surface water are currently very low to low, however adverse effects have still been observed in aquatic species + birds * The adverse effects of pharmaceuticals on humans are well known as they must go through extensive pre-clinical and clinical trials before they are put on the market. * Making it possible to predict the adverse effects of pharmaceuticals in drinking water on the human population. * Though it is still difficult to predict the effects on aquatic animal and plant life. ### Ways Pharmaceuticals Enter the Environment #### Use in Agriculture * Use of antibiotics in agriculture is the primary factor in the increased levels of antibiotics in groundwater and soils. * Will eventually end up in waterways. #### Treatment of Pets * Pharmaceuticals given to pets will be metabolized and excreted, and will find their way into surface and groundwater systems. #### Disposal of Medication * 25% of all unused drugs are washed down the sink or flushed down the toilet, which end up in sewage discharge. * 30% are thrown into the garbage and disposed of in a landfill, which can contaminate groundwater. #### Aquaculture * Antibiotics are used extensively in aquaculture. * Used to prevent disease and promote rapid growth to maturity. * Aquaculture is concentrated at certain locales, so high local concs of the antibiotics may exist. * A percentage of all drugs consumed by humans are excreted unchanged, or as active metabolites. * They will pass into the municipal wastewater systems. * Treatment of sewage may or may not remove the pharmaceutical prior to the entry into the environment. #### Manufacturing Processes * Pharmaceutical discharge from manufacturing plants have a major effect in local surface and groundwater. * Their impact will increase over time as more and more chemical facilities are moving to developing countries. ### Major Classes of Pharmaceuticals in the Environment #### Neuroreactive Drugs (antidepressants, antiepileptics, etc.) * Usage has increased 60% in the last decade. * Sewage treatment plants reduce but do not effectively remove these drugs from the sewage/wastewater. * Effect on humans appears to be minimal. * Concerns about selective serotonin reuptake inhibitor antidepressants in surface waters potentially causing deleterious effects on the reproductive and physiological development of fish. #### Steroid Hormones * Those that are estrogen compounds are of the most concern. * Sources include: oral contraceptives and excretion of natural estrogens by animals. * Current concs are well below the level where effects are observed. * Major concerns: * Their additive effect. * Their deleterious effect on the reproductive capacity and sexual maturation of aquatic animals (even at low concs). #### Hypertensive Drugs (high blood pressure) * 50% of Canadians are treated daily for hypertension. * Most have been measured in surface water, but concs are well below the levels that would be toxic to humans. * Though it is still unknown whether these compounds are biomagnified in the food chain and what conc is in the seafood we eat. #### Analgesics (pain relievers (ibuprofen, NSAIDS, etc.)) ## Chemotherapy * The use of drugs to kill cancer cells. * Chemotherapeutic Drug Classes: * **Alkylating agents** - bind to and interfere with DNA replication. * **Mitotic inhibitors** - affect microtubule function and the formation of the mitotic spindle, thereby preventing cell division. * **Hormones and hormone antagonists** - used to treat hormone sensitive tumors by suppressing cell division. * **Biologicals** - drugs derived through molecular biological techniques that inhibit cell replication by blocking cytokines which normally control cell growth. ### Principles of Cancer Chemotherapy * **Benefit-Risk Assessment** * Health team and patient must weigh the possible benefits vs adverse effects of treatment in each clinical situation. * Each type of cancer therapeutic is ssociated with its own toxicities. * **Combination Chemotherapy** * Chemotherapeutics are often used in combination * To prevent the development of resistance * To limit/minimize the occurrence of toxicities * Bc they tend to have low therapeutic indexes.