10 Environmental Health and Toxicology PowerPoint® Slides prepared by Jay Withgott and April Lynch

This lecture will help you understand: Environmental health hazards Environmental health goals Synthetic and natural toxicants The study of hazards and their effects Risk assessment and risk management Policy and regulation

Central Case: Alligators and Endocrine Disruptors at Lake Apopka, Florida Biologist Louis Guillette found alligators with reproductive abnormalities in a Florida lake. The lake had been contaminated with pesticides. Research revealed that chemicals in the lake were disrupting the animals’ reproductive hormones.

Environmental health Assesses environmental factors that influence human health and quality of life Seeks to prevent adverse effects on human health and ecological systems Contains environmental toxicology within its scope

Environmental health hazards Types include: • Physical hazards (floods, blizzards, landslides, radon, UV exposure) • Chemical hazards (disinfectants, pesticides) • Biological hazards (viruses, bacterial infections) • Cultural or lifestyle hazards (drinking, smoking, bad diet, crime in neighborhood)

Environmental health hazards LE 10-1 Physical hazard Chemical hazard Biological hazard Cultural hazard

Infectious disease In communicable or transmissable disease, a pathogen attacks a host, either directly or through a vector (e.g., mosquito that transfers a malaria parasite to hosts) … and the pathogen can be transmitted from one host to another. Infectious disease causes 25% of deaths in the world and nearly half of deaths in developing nations.

Annual deaths (millions) Infectious disease LE 10-2 4.0 Respiratory and digestive diseases Other 3.5 3.0 Maternal and perinatal conditions 7.9% 2.5 10.0% Infectious diseases 14.9 million 26.1% Annual deaths (millions) 2.0 5.2% 1.5 9.1% Injuries Cardiovascular diseases 29.3% 1.0 12.5% 0.5 Cancers Respiratory infections (influenza, pneumonia, etc.) AIDS Diarrheal diseases TB Malaria Childhood diseases (measles, Pertussis, tetanus, etc.) Leading causes of death across the world, 2004 Leading causes of death by infectious disease, 2004

Many health hazards also exist indoors Substances in plastics and consumer products Lead in paint and pipes Radon Asbestos PBDE fire retardants

Toxicology …is the study of poisonous substances and their effects on humans and other organisms. Toxicologists assess and compare toxic agents, or toxicants, for their toxicity, the degree of harm a substance can inflict. Environmental toxicology focuses on effects of chemical poisons released into the environment.

Environmental toxicology Toxicants are studied that come from or are discharged into the environment and their: Health effects on humans Effects on animals Effects on ecosystems Animals are studied: For their own welfare As “canaries in a coal mine” to warn of effects on humans

Synthetic chemicals are everywhere in our environment Many thousands have been produced and released. Some persist for long time periods or travel great distances. Of the 100,000 synthetic chemicals on the market today, very few have been thoroughly tested for harmful effects. 2002 USGS study: 80% of U.S. streams contain up to 82 wastewater contaminants, including antibiotics, perfumes, detergents, drugs, steroids, disinfectants, and so forth.

Rise of synthetic chemicals There has been widespread synthetic chemical production since WWII. People were largely unaware of the health risks of many toxicants. The potent insecticide DDT was sprayed widely in public areas, even on people.

Silent Spring and Rachel Carson Carson’s 1962 book alerted the public that DDT and other pesticides could be toxic to animals and people. Further research led the EPA to ban DDT in 1973. These developments were central to the modern environmental movement.

Types of toxicants Carcinogens: cause cancer Mutagens: cause mutations in DNA Teratogens: cause birth defects Allergens: cause unnecessary immune response Neurotoxins: damage nervous system Endocrine disruptors: interfere with hormones

Endocrine disruption Some chemicals, once inside the bloodstream, can “mimic” hormones. If molecules of the chemical bind to the sites intended for hormone binding, they cause an inappropriate response. Thus these chemicals disrupt the endocrine (hormone) system.

Normal hormone binding LE 10-4 Hormone Response Receptor Cell membrane Inside cell Normal hormone binding Hormone mimic Hormone Response (identical to that caused by hormone) Receptor Cell membrane Inside cell Hormone mimicry

Endocrine disruption The hormone system is geared to working with tiny concentrations of hormones … … so, it can respond to tiny concentrations of environmental contaminants. Have chemicals in the environment acted as endocrine disruptors in humans?

Frogs, people, and atrazine Frogs show reproductive abnormalities in response to small doses of the herbicide atrazine, researcher Tyrone Hayes has found. Others suggest that atrazine may have effects on humans as well. The fierce criticism from atrazine’s manufacturer reflects the high stakes in environmental toxicology.

Declining sperm counts? A 1992 study summarized results of sperm count studies worldwide since 1938. Data showed a significant decrease in men’s sperm counts over 50 years.

Declining sperm count in humans, based on 61 studies LE 10-6a Declining sperm count in humans, based on 61 studies

Testicular cancer Others hypothesize that endocrine disruptors are behind the rise in testicular cancer in many nations.

Increasing incidence of testicular cancer LE 10-6b Denmark Norway Germany Sweden Finland Estonia Increasing incidence of testicular cancer

Toxicants move in specific ways Synthetic chemicals take many routes in traveling through the environment.

Industry and manufacturing Human fetuses and babies LE 10-7 Industry and manufacturing Consumer products Medicines and materials Pesticides and fertilizers Waste Waste Waste Workplace products Medical facilities and public spaces Agriculture: crops, rangeland, feedlots Water: surface and groundwater Home Work Soil Air Workplace exposure Medicines and materials Food Consumer products Plant growth Drinking water Air for breathing Drinking water Non-target effects Air for breathing Humans Hunting and harvesting Genes, womb, breast milk Non-human biota Human fetuses and babies

Toxicants concentrate in water Surface water and groundwater can accumulate toxicants. Runoff from large areas of land drains into water bodies, becoming concentrated. Toxicants in groundwater or surface water reservoirs used for drinking water pose potential risks to human health.

Airborne toxicants Volatile chemicals can travel long distances on atmospheric currents. PCBs are carried thousands of miles from developed nations of the temperate zone up to the Arctic, where they are found in tissues of polar bears and seals.

Persistence Some chemicals are more stable than others, persisting in the environment. DDT and PCBs are persistent. Bt toxin in GM crops is not persistent. Temperature, moisture, sun exposure, and so forth, affect the rate of degradation. Most toxicants degrade into simpler breakdown products. Some of these are also toxic. (DDT breaks down to DDE, also toxic.)

Poisons accumulate in tissues The body may excrete, degrade, or store toxicants. Fat-soluble ones are stored. DDT is persistent and fat soluble, … so it builds up in tissues: bioaccumulation. Bioaccumulated chemicals may be passed on to animals that eat the organism—up the food chain…

Poisons move up the food chain At each trophic level, chemical concentration increases: biomagnification. DDT concentrations increase from plankton to fish to fish-eating birds.

LE 10-8 DDT concentration (parts per million) Osprey 25 ppm Large fish 2 ppm Small fish 0.5 ppm Zooplankton 0.04 ppm Water 0.000003 ppm

Not all toxicants are synthetic Although toxicology tends to focus on man-made chemicals, it’s important to keep in mind that there are plenty of natural toxicants. Many are toxins produced by animals or plants for protection against predators and pathogens.

Studying effects of hazards Toxicologists study effects in several major ways: • Wildlife toxicology studies • Human epidemiological studies • Dose-response studies in the lab

Approaches in environmental health research Human studies rely on: Case history = observation and analysis of individual patients Epidemiological studies = long-term, large-scale comparisons of different groups of people Animal testing

Epidemiology Advantages: Realistic All real-life factors included Disadvantages: Statistically correlational only; does not prove causation Takes many years to get results

Mixing toxicology with anthropology Mexican children were tested for pesticide effects. From The Science behind the Story

Drawings by children in the foothills LE 10-SBS 4-year-olds 5-year-olds Drawings by children in the foothills 4-year-olds 5-year-olds Drawings by children in the valley

Dose-response analysis Dose-response analysis is a method of determining the toxicity of a substance by measuring response to different doses. Lab animals are used. Mice and rats breed quickly and give data relevant to humans because they share mammal physiology with us. Responses to doses are plotted on a dose-response curve.

Dose-response curve LD50 = dose lethal to 50% of test animals Threshold = dose at which response begins

Dose-response curve Dose-response curves allow us to predict effects of higher doses. By extrapolating the curve out to higher values, we can predict how toxic a substance may be to humans at various concentrations. In most curves, response increases with dose. But this is not always the case; the increase may not be linear. With endocrine disruption, it may decrease.

Factors affecting toxicity Not all people are equal. Sensitivity to a toxicant can vary with sex, age, weight, and so forth. Babies, older people, or those in poor health are more sensitive. Type of exposure: acute = high exposure in short period of time chronic = lower amounts over long period of time

Mixtures of toxicants Substances may interact when combined together. Mixes of toxicants may cause effects greater than the sum of their individual effects. These are called synergistic effects. A challenging problem for toxicology: There is no way to test all possible combinations! (And the environment contains complex mixtures of many toxicants.)

Risk Risk = the mathematical probability that some harmful outcome will result from a given action, event, or substance Probability = a quantitative description of the likelihood of a certain outcome “Harmful outcome” could be defined as injury, death, environmental damage, or economic loss

Perception differs from reality Our perception of risks tends not to match statistical reality. smoking plane crash

Risk assessment Analyzes risks quantitatively Measures and compares risks involved in different activities or substances Helps identify and prioritize serious risks Helps determine threats posed to humans, wildlife, and ecosystems

Risk management Considers risk assessments in light of social, economic, and political needs and values Weighs costs and benefits, given both scientific and nonscientific concerns Results in decisions whether or not to reduce or eliminate risk

Risk assessment and risk management inform policy Following risk management, policy decisions are made.

ethical considerations LE 10-11 Scientific results and measurement of probability Political, social, economic, and ethical considerations Risk assessment Risk management Policy Scientific data on Information, opinion, and lobbying from Hazard identification Toxicity character- ization Extent of exposure Private citizens Industry and manufacturing Nonprofit Interest groups

Philosophical approaches “Innocent until proven guilty”: Assume harmless until shown to be harmful Precautionary principle: Assume harmful until shown to be harmless

Implications for product testing “Innocent until proven guilty”: Industry can introduce any products it wants. Government bears the burden of proof to show if products are dangerous. Precautionary principle: Industry cannot introduce a product until it is very thoroughly tested and shown convincingly to be harmless.

Implications for product testing Industry has pressured government to take an “innocent-until-proven-guilty” approach. Environmental advocates have pressured government to follow the precautionary principle.

“Innocent until proven guilty” approach Precautionary LE 10-12 “Innocent until proven guilty” approach Precautionary principle approach Sequence of events Industrial research and development Pre-market testing by industry, government, and academic scientists Limited testing; all products brought to market Rigorous testing; only the safest products brought to market Consumer use of products Some products harm human health Minimal impact on human health Post-market testing by industry, government, and academic scientists Rigorous testing demanded Limited testing required Regulations and bans of unsafe products Unsafe products recalled Consumer use of safe products

Federal agencies and risk management In the United States, most risk management is conducted by federal and state agencies. Particularly: Environmental Protection Agency and Food and Drug Administration

Policy on toxicants Key agencies and products they regulate: Food and Drug Administration (FDA) food, additives, cosmetics, drugs, medical devices Environmental Protection Agency (EPA) pesticides, industrial chemicals, and any synthetic chemicals not covered by other agencies Occupational Health and Safety Administration (OSHA) workplace hazards

EPA regulation: Pesticides Pesticides to be introduced to market in the United States need to be registered with the EPA. Registration involves risk assessment and risk management. The EPA assesses research from the manufacturer along with any outside research. The EPA can set restrictions on use, or even ban a product.

EPA regulation: Industrial chemicals The EPA is charged with monitoring 75,000 industrial chemicals. There are too many chemicals and not enough time, people, or resources. Only 10% of chemicals on the market are thoroughly tested. Only 2% are screened for carcinogens, mutagens, and teratogens. <1% are government regulated. ~0% are tested for endocrine, nervous, or immune effects.

International policy on toxicants The EU has proposed legislation to require 30,000 chemicals to be tested and registered, and 1,500 hazardous chemicals to be restricted. Stockholm Convention, 2001: international treaty to phase out 12 persistent organic pollutants (POPs), “the dirty dozen”

Viewpoints: Industry or government? Warren Porter Marian Stanley “Given the inherent inadequacies of the testing process and the uncertainty of the economic impacts, both government and industry should share the responsibility of testing to ensure public safety.” “Manufacturers often voluntarily conduct new studies to support the continued safe use of their chemicals. … It is important that the EPA and manufacturers work together in evaluating chemicals.”

Conclusion International agreements are a hopeful sign that governments will control environmental hazards. But solutions may come more easily when they do not arise from government regulation alone. Consumer choice can influence industry if consumers have accurate information. But we will never attain complete knowledge of risks. A safer future depends on knowing risks, phasing out harmful substances, and replacing them with safer ones.

QUESTION: Testing Your Comprehension Which causes birth defects? a. Allergen b. Mutagen c. Carcinogen d. Teratogen e. Endocrine disruptor

QUESTION: Testing Your Comprehension Which causes birth defects? d. Teratogen

QUESTION: Testing Your Comprehension Which statement is NOT correct regarding the insecticide DDT? a. It was criticized in the book Silent Spring. b. It helps fight malaria. c. It is persistent and bioaccumulates. d. It has no toxic breakdown products. e. Its use was banned by the EPA.

QUESTION: Testing Your Comprehension Which statement is NOT correct regarding the insecticide DDT? d. It has no toxic breakdown products.

QUESTION: Testing Your Comprehension Epidemiological studies… ? a. Can prove a certain toxicant causes a certain effect. b. Search for statistical association between hazard and effect. c. Are rapidly completed. d. Take place with lab animals.

QUESTION: Testing Your Comprehension Epidemiological studies… ? b. Search for statistical association between hazard and effect.

QUESTION: Testing Your Comprehension Which statement is FALSE? a. Babies are more sensitive to toxicants than 30- year-olds. b. Synergistic effects can occur with mixtures of chemicals. c. Chronic exposure occurs over a short period of time. d. Some doses may elicit no measurable response.

QUESTION: Testing Your Comprehension Which statement is FALSE? c. Chronic exposure occurs over a short period of time.

QUESTION: Seeking Solutions Describe some environmental hazards you think you may be living with indoors. How do you think you may have been affected by indoor or outdoor environmental hazards? What steps do you plan to take to deal with these toxicants in your own life?

QUESTION: Seeking Solutions Do you feel laboratory-bred animals should be used in experiments on toxicology? Why or why not? Can you envision any alternatives?

QUESTION: Viewpoints In testing new synthetic chemicals, should we follow the “innocent-until-proven-guilty” approach, or the precautionary principle? a. “Innocent-until-proven-guilty” approach b. Precautionary principle c. A hybrid of both approaches