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18
Principles of Toxicology and
Risk Assessment
Chapter Outline
Principles of Toxicology
The Biological Effects of Toxicants
How Toxicants Work
Factors That Affect the Toxicity of Chemicals
Mutations, Cancer, and Birth Defects
Mutations
Cancer
Birth Defects
Reproductive Toxicity
Environmental Hormones
Case Studies: A Closer Look
Asbestos: How Great a Danger?
Electromagnetic Radiation: A Hazard to Our Health?
Controlling Toxic Substances: Toward a Sustainable Solution
Toxic Substances Control Act
Market Incentives to Control Toxic Chemicals
The Multimedia Approach to Pollution Control: An Integrated Approach
Risk and Risk Assessment
Risks and Hazards: Overlapping Boundaries
Three Steps in Risk Assessment
Risk Acceptability
How Do We Decide If a Risk Is Acceptable?
The Final Filter: Ethics and Sustainability
Key Terms
pollution prevention toxicology toxicants
enzymes mutations hypersensitized
dose dose-response curve duration of exposure
acute chronic additive response
synergistic response potentiation bioaccumulation
biological magnification mutations mutagens
somatic cells germ cells cancer
benign tumor malignant tumor primary tumor
metastasis secondary tumor DNA-reactive carcinogens epigenetic carcinogens biotransformation birth defects
teratogens teratology organogenesis
stillbirth reproductive toxicity environmental hormones
asbestosis electromagnetic radiation polychlorinated biphenyls
premanufacture notification pollution taxes green taxes
tradable permits multimedia approach anthropogenic hazards
natural hazards risk assessment hazard identification
estimation of risk threshold level risk acceptability
perceived harm perceived benefit cost-benefit analysis
space-time values
Objectives
1. Define the following terms: “immediate toxicity,” “delayed toxicity,” “local effects” and “systemic effects.”
2. List the three ways toxins are known to act at the cellular level.
3. List several factors that may affect the toxicity of chemicals.
4. Define the following terms: “dose,” “dose-response curve,” “LD50,” and “duration of exposure.”
5. Give an example of biomagnification in the environment.
6. Define the following terms and give an example of each: “toxin,” “mutagen,” “carcinogen,” and “teratogen.”
7. Discuss the health effects of reproductive toxicants and environmental hormones.
8. Summarize the primary legislation regulating exposure to toxic substances in the United States.
9. Discuss some sustainable solutions to control the use of toxic substances.
10. Discuss the major sources of lead pollution, the health effects produced by exposure to lead, and the ways in which human exposure can be reduced.
11. List the three steps used in risk assessment.
12. Discuss how we decide if a risk is acceptable.
13. Discuss the influence of ethics on our decisions concerning environmental risks.
Lecture Outline
Principles of Toxicology - Sixty thousand chemical substances are used commercially in the United States. Of these, relatively few pose serious risks, yet those risks are substantial. Due to economic and time constraints, only a small percentage of potentially harmful chemicals are tested for sub-acute toxicity.
A. The Biological Effects of Toxins
Immediate and Delayed Toxicity
Acute or immediate effects appear shortly often exposure and may be quite severe; they are usually the result of high-concentration, short-term exposures.
Chronic effects are delayed responses generally due to long-term, low-level exposure.
Reversible and Irreversible Toxic Effects
While damage from exposure to some toxins is reversible, in other cases the damage is chronic or even lethal.
Local and Systemic Toxic Effects
Some toxins exert effects at only a localized site; others may affect an entire organ or organ system.
How Toxins Work
Toxins disrupt cellular metabolism in a variety of ways.
Factors Affecting the Toxicity of Chemicals
Dose and Duration of Exposure
Higher doses and longer exposures tend to increase toxic effects.
The LD50 is the dose of a toxin lethal to 50% of the test animals.
Biological Activity and Route of Exposure
Biological activity is a measure of a substance's reactivity in living systems.
A toxin's route of entry determines how easily it enters the bloodstream and thus influences its effects.
Age
Younger organisms are usually more sensitive to toxins than are adults.
Health Status
Genetic predisposition and one's lifestyle may influence one's susceptibility to the effects of toxins.
Chemical Interactions
Two or more toxic substances present together can alter the expected response. A synergistic response is one in which the results are amplified; an antagonistic response is one in which the effects are negated; potentiation is the effect a nontoxic chemical has in intensifying the effect of a toxin.
Bioaccumulation and Biological Magnification
a. Bioaccumulation is the accumulation of certain chemicals in the body.
b. Biological magnification is the buildup of chemicals through a food chain.
Mutations, Cancer, and Birth Defects
Mutations
Mutations are alterations of the genetic material.
Agents that cause mutations are mutagens.
Mutations of germ-cells can be passed from one generation to the next.
Cancer
Cancer is an uncontrolled proliferation of cells, caused by one of a variety of agents or carcinogens.
Environmental factors, food additives and other products, and occupational exposure account for most cancers not due to smoking.
Birth Defects
These are physical, biochemical, or functional abnormalities.
Agents that cause birth defects are teratogens; their effects depend on timing of exposure and the nature of the teratogen.
Reproductive Toxicity
Many drugs and environmental agents can interfere with reproduction; the study of these is reproductive toxicology.
Environmental Hormones
A. Environmental hormones are chemical pollutants that enter organisms and can alter or mimic the body’s natural release of hormones. Hormones are regulatory chemicals produced by organs in the body.
Case Studies: A Closer Look
Asbestos: How Great a Danger
Asbestos is a naturally occurring element. It produces three serious disorders:
pulmonary fibrosis
lung cancer
mesothelioma
Asbestos is dangerous to asbestos workers and individuals who smoke.
The use of asbestos in the United States for insulation, fireproofing, and decorative purposes was banned in 1974. Further regulations enacted by the EPA in 1989 will eliminate almost 95% of all asbestos use in the United States.
Electromagnetic Radiation: A Hazard to Our Health?
Studies on the effects of extremely low-frequency (ELF) magnetic fields have been inconclusive up to this point.
Controlling Toxic Substances: Toward a Sustainable Solution
Federal Control
The Toxic Substances Control Act is intended to screen and regulate chemicals to minimize human health risk.
The Act requires premanufacture notification, testing, and hazard minimization.
Market Incentives to Control Toxic Chemicals
In California, a law requires manufacturers to either meet state-set standards for toxins or label their products accordingly, thus reducing the marketability of those products not in compliance.
The Multimedia Approach to Pollution Control
By training inspectors in several environmental media, the EPA hopes to control cross-media contamination.
Risk and Risk Assessment
Risks and Hazards: Overlapping Boundaries
Risk is a relative assessment of the threat posed by anthropogenic and natural hazards.
Three Step in Risk Assessment
Through hazard identification and risk estimation, risk assessment seeks to help us understand and quantify risks in our lives.
Risk assessment is necessarily imprecise due to the nature of probability and severity estimates.
Due to the threshold level of many toxins, it is difficult to extrapolate from lab animals to humans in toxicity tests where high doses are used to speed and make observable any toxic effects.
Risk Acceptability
Since all activities involve some degree of risk, this is a relative term.
Risk acceptability is influenced by fear, perceived benefit, and perceived harm.
How Do We Decide If a Risk Is Acceptable?
Deciding which risks to accept in order to procure benefits involves tradeoffs.
Cost/benefit analysis is a popular decision-making tool though it is impossible to accurately quantify all benefits and costs relevant to most risk decisions.
Actual Versus Perceived Risk
When actual and perceived risk do not coincide, the result may be legislative over- or under-protection.
The Final Filter: Ethics and Sustainability - Ultimately, our values determine our attitudes with regard to environmental risks.
Prioritizing Values
Our values must be prioritized in order for us to weigh and assess relative risks.
Space-Time Values
Our values also reflect certain spatial and temporal parameters that influence our decision-making.
Building a Sustainable Future
It is incumbent upon us to build a future in which risks are realistically assessed and minimized and where, if errors are made, they are made on the side of safety.
Suggestions for Presenting the Chapter
Ÿ Instructors should encourage the students to identify important environmental risks in their lives. How can we reduce or eliminate these risks? Are these risks associated with unsustainable systems/activities in our lives? How can these systems/activities be modified to become sustainable?
Ÿ A good exercise is to have students identify toxic chemicals in their homes. Students can be asked to research the harmful effects of the chemicals found and share their results in class or in a paper.
Ÿ Radon tests are easily performed and can be done in class at your educational institution. The results of these tests and the interpretation of those results provide a good review of the principles of toxicology. Students can be encouraged to perform radon tests in their own homes.
Ÿ Cancer is an excellent topic to explore with your classes. Today, much research is being done on the environmental aspects of our current epidemic. This is very relevant topic with students since few of us have not been affected in some way by this disease.
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