Toxicology & risk

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Environmental Health, Risk and Toxicology


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

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

Synthetic and natural toxicants are only one type of environmental health threat. Others are:

• 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)


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 worldand nearly half of deaths in developing nations.


Infectious disease

2nd-leading cause of death worldwide

6 diseases account for 80% of infectious disease deaths


Many health hazards exist indoors

• Substances in plastics and consumer products

• Lead in paint and pipes

• Radon

• Asbestos

• PBDE fire retardants


Toxicology

• 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.

• Analagous to a pathogenicity or virulence of the biological hazards that spread infectious disease.

• Environmental toxicology focuses on effects of chemical poisons released into the environment.


Environmental toxicology

• Studies toxicants that come from or are discharged into the environment, and:

• 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.

• 2002 USGS study: 80% of U.S. streams contain up to 82 wastewater contaminants, include antibiotics, perfumes, detergents, drugs, steroids, disinfectants, etc.


Synthetic chemicals

Of the 100,000 synthetic chemicals on the market today, very few have been thoroughly tested for harmful effects.


Synthetic chemicals are numerous


Rise of synthetic chemicals

• Widespread synthetic chemical production after WWII

• People are 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


Types of toxicants: Teratogens

The drug thalidomide, used to relieve nausea during pregnancy, turned out to be a potent teratogen, and caused thousands of birth defects before being banned in the 1960s.

“Thalidomide baby” Butch Lumpkin learned to overcome his deformed arms and fingers to become a professional tennis instructor.


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.


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.


Testicular cancer

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


Toxicants take many routes through the environment


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.


Transport to the Arctic: “Global distillation”


Persistence• Some chemicals are more stable than others, persisting

for longer in the environment.

• DDT and PCBs are persistent.• Bt toxin in GM crops is not persistent.

• Temperature, moisture, sun exposure, etc., affect 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 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.


All toxicants are not 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


Wildlife toxicology

• Determine causes of mortality in die-off events (e.g., toxoplasma)

or

• Test animals in the lab for response to toxicants

or

• Correlate chemical presence and animal presence in the field


Human epidemiology

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


Human 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

Children were tested for pesticide effects.

Drawings by nonexposed children

Drawings by exposed children


Dose-response analysis

• Method of determining 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 toxicant can vary

with sex, age, weight, etc.

• 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.)


Policy on toxicantsKey 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


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, economic loss, etc.


Perceiving Risk

• Most individuals evaluate the relative risk they face based on:

- Degree of control.

- Fear of unknown.

- Whether we voluntarily take the risk.

- Whether risk is catastrophic.

- Unfair distribution of risk.

• Sometimes misleading information, denial, and irrational fears can cloud judgment.


Perception different from reality

Our perception of risks tends not to match statistical reality. smoking

plane crash


RISK ANALYSIS

• Annual deaths in the U.S. from tobacco use and other causes in 2003.

Figure 18-AFigure 18-A


RISK ANALYSIS

• Number of deaths per year in the world from various causes. Parentheses show deaths in terms of the number of fully loaded 400-passenger jumbo jets crashing every day of the year with no survivors.

Figure 18-13Figure 18-13


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, ecosystems


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.


“The dirty dozen” POPs• Aldrin (insecticide)

• Chlordane (insecticide)

• DDT (insecticide)

• Dieldrin (insecticide)

• Dioxins (industrial by-product)

• Endrin (insecticide)

• Furans (industrial by-product)

• Heptachlor (insecticide)

• Hexachlorobenzene (fungicide, industrial by-product)

• Mirex (insecticide, fire retardant)

• PCBs (industrial chemical)

• Toxaphene (insecticide)


Conclusion

• International agreements are a hopeful sign that governments will prevent environmental hazards.

• But solutions can come more easily when they do not arise from government regulation alone.

• Consumer choice can influence industry if consumers have scientific 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.

Toxicology & risk

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