The complexity of the biological risks humans face is matched by the complexity of chemical risks. Our modern society has developed an incredible array of chemicals to improve human health and food production, including pharmaceuticals, insecticides, herbicides, and fungicides. We have also seen that chemical by-products from manufacturing and the generation of energy can be harmful to humans and the environment. Even beneficial chemicals, when released into the environment, can harm humans and other organisms. Many pharmaceuticals, for example, have unexpected consequences when released into the environment. In this module we will look at the types of chemicals that can have harmful effects. We will see how scientists study these chemicals, and what effect the chemicals have on humans.

Learning Objectives

After reading this module you should be able to

Chemicals can have many different effects on organisms, and some of the most harmful are common in our environment; TABLE 57.1 lists those of current concern. They can be grouped into five categories: neurotoxins, carcinogens, teratogens, allergens, and endocrine disruptors.

Neurotoxins

Neurotoxins are chemicals that disrupt the nervous systems of animals. Many insecticides, for example, are neurotoxins that interfere with an insect’s ability to control its nerve transmissions. Insects and other invertebrates are highly sensitive to neurotoxin insecticides. These animals can become completely paralyzed, cannot obtain oxygen, and quickly die. Other important neurotoxins include lead and mercury. As we discussed in Chapters 14 and 15, lead and mercury are very harmful heavy metals that can damage the human kidneys, brain, and nervous system. As shown in FIGURE 57.1, since the federal government required a gradual elimination of lead in gasoline and paint in the 1970s, lead exposure in the United States has declined sharply. However, lead contamination in children remains a serious problem in low-income neighborhoods due to the presence of old lead paint in buildings. Mercury also remains a major problem.

Carcinogens

Carcinogens are chemicals that cause cancer. Carcinogens cause cell damage and lead to uncontrolled growth of these cells either by interfering with the normal metabolic processes of the cell or by damaging the genetic material of the cell. Carcinogens that cause damage to the genetic material of a cell are called mutagens (although not all mutagens are carcinogens). Some of the most well-known carcinogens include asbestos, radon, formaldehyde, and the chemicals found in tobacco.

Teratogens

Teratogens are chemicals that interfere with the normal development of embryos or fetuses. One of the most infamous teratogens was the drug thalidomide, prescribed to pregnant women during the late 1950s and early 1960s to combat morning sickness. Sadly, tens of thousands of these mothers around the world gave birth to children with defects before the drug was taken off the market in 1961 (FIGURE 57.2). One of the most common modern teratogens is alcohol. Excessive alcohol consumption reduces the growth of the fetus and damages the brain and nervous system of the fetus, a condition known as fetal alcohol syndrome. This is why physicians recommend that women not consume alcoholic beverages while they are pregnant.

Allergens

Allergens are chemicals that cause allergic reactions. Although allergens are not pathogens, allergens are capable of causing an abnormally strong response from the immune system. In some cases, this response can cause breathing difficulties and even death. Typically, a given allergen only causes allergic reactions in a small fraction of people. Some common chemicals that cause allergic reactions include the chemicals naturally found in peanuts and milk and several drugs including penicillin and codeine.

Endocrine Disruptors

Endocrine disruptors are chemicals that interfere with the normal functioning of hormones in an animal’s body. Hormones are normally manufactured in the endocrine system and released into the bloodstream in very low concentrations. As the hormones move through the body, they bind to specific cells. Binding stimulates the cell to respond in a way that regulates the functioning of the body including growth, metabolism, and the development of reproductive organs. As FIGURE 57.3 shows, an endocrine disruptor can bind to receptive cells and cause the cell to respond in ways that are not beneficial to the organism.

One high-profile example of endocrine disruptors in our environment is the group of reproductive hormones that can be found in wastewater. As we discussed in Chapter 14, wastewater may contain hormones from a variety of sources including animal-rearing facilities, human birth control pills, and pesticides that mimic animal hormones. In waterways exposed to hormones through wastewater, scientists are increasingly finding that male fish, reptiles, and amphibians are becoming feminized; males possess testes that have low sperm counts and, in some cases, testes that produce both eggs and sperm. Males normally convert the female hormone estrogen into the male chemical testosterone. Reproductive hormones in wastewater can interfere with the production of testosterone, which causes males to have higher concentrations of estrogen and lower concentrations of testosterone in their bodies. Such discoveries raise serious concerns about whether endocrine disruptors might affect the normal functioning of human hormones. These effects include low sperm counts in men and an increased risk of breast cancer in women.

To assess the risk a chemical poses, we need to know the concentrations that cause harm. Scientists have three techniques to determine harmful concentrations: dose-response studies, prospective studies, and retrospective studies.

Dose-Response Studies

Dose-response studies expose animals or plants to different amounts of a chemical and then look for a variety of possible responses including mortality or changes in behavior or reproduction. For example, dose-response studies of aquatic animals such as tadpoles are used to determine the concentrations of various pesticides that cause 50 percent of the animals to die (FIGURE 57.4). The concentration of the chemicals being considered can be measured in air, water, or food. They can also be measured as the dose of a chemical, which is the amount that an organism absorbs or consumes. For reasons of efficiency, most dose-response studies only last for 1 to 4 days. Experiments that expose organisms to an environmental hazard for a short duration are called acute studies. Studies that are conducted for longer periods of time are called chronic studies.

Dose-response studies most commonly measure mortality as a response. At the end of a dose-response experiment, scientists count how many individuals die after exposure to each concentration. When the data are graphed, they generally follow an S-shaped curve, like the one in FIGURE 57.5. If you examine the purple curve, you will see that at the lowest dose no individuals die. At slightly higher doses, a few individuals die. The dose at which an effect can be detected is called the threshold. These individuals generally are in poorer health or genetically are not very tolerant to the chemical. As the dose is further increased, many more individuals begin to die. At the highest concentrations all individuals die.

To compare the harmful effects of different chemicals scientists measure the LD50, which is an abbreviation for the lethal dose that kills 50 percent of the individuals in a dose-response study. The LD50 value helps assess the relative toxicity of a chemical to a particular species. For example, scientists can compare the LD50 value of a new chemical with the LD50 value of thousands of previously tested chemicals to determine whether the new chemical is more or less lethal to a given organism than other chemicals.

Although the vast majority of toxicology studies are only conducted for a few days, chronic studies will often last from the time an organism is very young to when it is old enough to reproduce. For some species such as fish, chronic experiments can take several months. The goal of chronic studies is to examine the long-term effects of chemicals, including how they affect survival and reproduction.

Not all dose-response experiments measure death as a response to chemicals. In many cases, scientists are interested in other harmful effects, including acting as a teratogen, carcinogen, or neurotoxin. When exposure to a chemical does not kill an organism but impairs its behavior, physiology, or reproduction, we say the chemical has sublethal effects. In these cases, the experiments are conducted to determine the ED50, which is the effective dose that causes 50 percent of the individuals in a dose-response study to display the harmful, but nonlethal, effect.

Testing Standards

In the United States, chemicals that affect humans and other species are regulated by the Environmental Protection Agency (EPA). The Toxic Substances Control Act of 1976 gives the EPA the authority to regulate many chemicals, but does not include food, cosmetics, and pesticides. Pesticides are regulated under a separate law—the Federal Insecticide, Fungicide, and Rodenticide Act of 1996. Under this act, a manufacturer must demonstrate that a pesticide “will not generally cause unreasonable adverse effects on the environment.”

Because no chemical can be tested on every one of the approximately 10 million species of organisms on Earth, scientists have devised a system of testing a few species—a bird, mammal, fish, and invertebrate—that are thought to be among the most sensitive in the world. The particular species tested from each of the four animal groups can vary, depending on which species is thought to be the most sensitive to a particular chemical. The reasoning for this is that regulations devised to protect the most sensitive species in a group will automatically protect all other species in that group. Since conducting LD50 studies on humans would be unethical, results from studies conducted on mice and rats are extrapolated to humans. For nonhuman animals, test results from mice and rats are used to represent all mammals, birds such as pigeons and quail are used to represent all birds, fish such as trout are used to represent all fish, and invertebrates such as water fleas are used to represent all invertebrates.

You might have noticed that the groups of tested animals do not include amphibians or reptiles. Unfortunately, the standards for testing chemicals were set up before there was much interest in protecting amphibians and reptiles. Currently, test results from fish are used to represent aquatic amphibians and reptiles, whereas test results from birds are used to represent terrestrial amphibians and reptiles. Because amphibians and reptiles are now experiencing population declines throughout the world, there is increased interest in requiring tests on species from these two groups as well.

Using the LD50 and ED50 values from dose-response experiments, regulatory agencies such as the EPA can determine the concentrations in the environment that should cause no harm. For most animals, a safe concentration is obtained by taking the LD50 value and dividing it by 10. The logic is that if the LD50 value causes 50 percent of the animals to die, then 10 percent of the LD50 value should cause few or no individuals to die.

The regulatory agencies, however, are much more conservative in setting concentrations for humans. Scientists determine the LD50 or ED50 values for rats or mice and then divide by 10 to determine a safe concentration for rats and mice. This value is divided by 10 again to reflect that rats and mice may be less sensitive to a chemical than humans. Finally, this value is often divided by 10 again to ensure an extra level of caution. In short, the LD50 and ED50 values obtained from rats and mice are divided by 1,000 to set the safe values for humans. “Do the Math: Estimating LD50 Values and Safe Exposures” on page 610 shows you how to make this calculation.

Retrospective versus Prospective Studies

Estimating the effects of chemicals on humans is a major challenge. We have seen that one approach is to conduct dose-response experiments on rats and mice and extrapolate the results to humans. An alternative approach is to examine large populations of humans or animals who are exposed to chemicals in their everyday lives and then determine whether these exposures are associated with any health problems. Such investigations fall within the study of epidemiology, a field of science that strives to understand the causes of illness and disease in human and wildlife populations. There are two ways of conducting this type of research: retrospective studies and prospective studies.

Retrospective studies monitor people who have been exposed to a chemical at some time in the past. In such studies, scientists identify a group of people who have been exposed to a potentially harmful chemical and a second group of people who have not been exposed to the chemical. Both groups are then monitored for many years to see if the exposed group experiences more health problems than the unexposed group. In 1984, for example, there was an accidental release of methyl isocyanate gas from a Union Carbide pesticide factory in Bhopal, India (FIGURE 57.6a). More than 36,000 kg (80,000 pounds) of hazardous gas spread through the city of 500,000 inhabitants. An estimated 2,000 people died that night and another 15,000 died later from effects related to the exposure. For more than 2 decades scientists have been monitoring many citizens of Bhopal to determine if survivors of the accident have developed any additional health problems. The retrospective studies have found that approximately 100,000 people are still suffering illnesses from the accidental exposure to the gas. The survivors have higher rates of genetic abnormalities, infant mortality, kidney failure, and learning disabilities. As shown in FIGURE 57.6b, they also have higher rates of respiratory problems and stillbirths.

In contrast to retrospective studies, prospective studies monitor people who might become exposed to harmful chemicals in the future. In this case, scientists might select a group of 1,000 participants and ask them to keep track of the food they eat, the tobacco they use, and the alcohol they drink over a period of several decades. As time passes, the researchers can determine if the habits of the participants are associated with any future health problems. Prospective studies can be quite challenging because a participant’s habits, such as tobacco use, can also be associated with many other risk factors, such as socioeconomic status. Of particular concern is when multiple risks cause synergistic interactions, in which two risks together cause more harm than expected based on the separate effects of each risk alone. For example, the health impact of a carcinogen such as asbestos can be much higher if an individual also smokes tobacco.

Studies of lead in children are often prospective. In one study, researchers at Harvard University looked at the effects of lead on children’s intelligence by following 276 children in Rochester, New York, from 6 months to 5 years of age. IQ tests are reliable at the age of 5. In addition to lead exposure, the researchers also accounted for other factors that might affect childhood IQ including the mother’s IQ, exposure to tobacco, and the intellectual environment of their homes. After controlling for these other factors, the researchers found that among children who had been exposed to lead in the environment—primarily from breathing lead dust and consuming lead paint chips—those with higher lead exposures scored lower on subsequent IQ tests. Such prospective studies can help regulators determine acceptable levels of chemical exposure.

Factors That Determine the Concentrations of Chemicals That Organisms Experience

Knowing the concentrations of chemicals that can harm humans or other animals is important, but it is only useful when combined with information about the concentrations that an individual might actually experience in the environment. If a chemical is quite harmful at some moderate concentration but individuals only experience lower concentrations of that chemical, we might not be particularly concerned. Therefore, to identify and understand the effects of chemical concentrations that organisms experience, we need to know something about how the chemicals behave in the environment.

Routes of Exposure

The ways in which an individual might come into contact with a chemical are known as routes of exposure. As FIGURE 57.7 illustrates, the full range of possibilities is complex because it includes potential exposures from the air, from water used for drinking, bathing, or swimming, from food, and from the environments of places where people live, work, or visit. For any particular chemical, however, the major routes of exposure are usually limited to just a few of the many possible routes. For example, bisphenol A is a chemical used in manufacturing hard plastic items such as toys, food containers, and baby bottles. Recent research has raised concerns that bisphenol A may be responsible for early puberty and increased rates of cancer. While these effects are being debated and investigated, it is clear that a child’s routes of exposure to bisphenol A are limited to toys, food containers, and baby bottles.

Solubility of Chemicals, Bioaccumulation, and Biomagnifications

Once we know the potential routes of exposure, scientists can then determine the chemical’s solubility and its potential for bioaccumulation and biomagnification. The movement of a chemical in the environment depends in part on its solubility, which is how well a chemical can dissolve in a liquid. For example, some chemicals such as herbicides are readily soluble in water whereas others such as insecticides are much more soluble in fats and oils. When a chemical is highly soluble in water, it can be washed off surfaces, percolate into groundwater, and run off into surface waters including rivers and lakes. In contrast, chemicals that are soluble in fats and oils are not very soluble in water so they tend not to be found percolating into the groundwater or running off into surface waters. Instead, they can be found in higher concentrations bound to soils, including the benthic soils that underlie bodies of water.

Chemicals that are soluble in fats and oils can also become stored in the fatty tissues of animals. For example, in Chapter 11 we mentioned that DDT accumulates in the fatty tissues of eagles and pelicans. This process, known as bioaccumulation, occurs when an organism increases the concentration of a chemical in its body over time. The process of bioaccumulation begins when an individual is exposed to small amounts of a chemical from the environment and incorporates the chemical into its tissues, typically its fat tissues. Fish, for example, are exposed to low concentrations of methyl mercury when they drink water, pass water over their gills to breathe, and consume food that contains mercury. A fish stores mercury in its fat tissues and, over time, the mercury accumulates. The rate of accumulation for any animal will depend on the concentration of the chemical in the environment, the rate at which the animal takes up each source of the chemical, the rate at which the chemical breaks down inside the animal, and the rate at which it is excreted by the animal.

Biomagnification is the increase in chemical concentration in animal tissues as the chemical moves up the food chain. In this way, the original concentration in the environment is magnified to occur at a much higher concentration in the top predator of the community. The classic example of biomagnification is the case of DDT, an insecticide that has been widely used to kill insect pests in agriculture and to kill the mosquitoes that carry malaria and other diseases. DDT is not soluble in water, so when sprayed over water it quickly binds to particulates in the water and the underlying soil or is quickly taken up by the tiny zooplankton that act as primary consumers on algae. As we see in FIGURE 57.8, the very low concentration of DDT in the water bioaccumulates in the bodies of the zooplankton where it becomes approximately 1,000 times more concentrated. Small fish eat the zooplankton for many weeks or months and the DDT is further concentrated approximately sixfold. Large fish spend their lives eating the contaminated smaller fish and the DDT in the large fish is further concentrated approximately fivefold. Finally, fish-eating birds such as pelicans and eagles spend years eating the large fish and further magnify the DDT in their own bodies. Because of biomagnification along the food chain, the concentration of DDT in the birds is nearly 276,000 times higher than the concentration of DDT in the water. The concentrated DDT in the fish-eating birds causes them to produce thin-shelled eggs that often break when the parent birds try to incubate the eggs. This was a primary cause in the decline of these birds in the 1960s. Since DDT was banned in the United States in 1972, the populations of fish-eating birds have dramatically increased.

Persistence

The persistence of a chemical refers to how long the chemical remains in the environment. Persistence depends on a number of factors including temperature, pH, whether the chemical is in water or soil, and whether it can be degraded by sunlight or broken down by microbes. Scientists often measure persistence by observing the time needed for a chemical to degrade to half its original concentration, known as the half-life of the chemical. TABLE 57.1 lists the persistence of various chemicals in the environment measured according to half-life. DDT, for example, has a half-life in soil of up to 30 years. Thus, even after DDT is no longer sprayed in an area, half of the chemical that was absorbed in the soil would still be present after 30 years, and one-fourth would be present after 60 years. Chemicals that cause harmful effects on humans and other organisms may become even larger risks when they persist for many years. For this reason, many modern chemicals are designed to break down much more rapidly so that any unintended effects will be short-lived.