Toxicology

Toxicology is the scientific study of poisons (or toxins). Major topics in toxicology include the detection and chemical analysis of poisons, the study of the metabolic effects of these substances on organisms, and the investigation of methods for treatment of poisoning.

The Swiss physician and alchemist Philippus Aureolus, also known as Paracelsus (1493-1541) and said to be the father of the modern science of toxicology, wrote "All things are poison, and nothing is without poison, the dose alone makes a thing not a poison." In other words, if poisoning is to be caused, an exposure to a potentially toxic chemical must result in a dose that exceeds a physiologically determined threshold of tolerance. Smaller exposures do not cause poisoning.

Physiology is the study how organisms function, and the disruption of biochemical pathways by poisons is a key aspect of toxicology. Poisons affect normal physiology in many ways, but some of the more common mechanisms involve the disabling of enzyme systems, induction of cancers, interference with the regulation of blood chemistry, and disruption of genetic processes.

Organisms vary greatly in their tolerance of exposure to chemicals, and even within populations of the same species there can be great variations in sensitivity. In rare cases, some individuals may be extremely sensitive to particular chemicals or groups of similar chemicals, a phenomenon known as hypersensitivity.

Organisms are often exposed to a wide variety of potentially toxic chemicals through medicine, food, water , and the atmosphere. Humans are exposed to complex mixtures of chemicals, many of which are synthetic and have been either deliberately or accidentally released into the environment.

In some cases, people actively expose themselves to chemicals that are known to be toxic, such as when smoking cigarettes, drinking alcohol , or taking recreational drugs. Voluntary exposure to chemicals also occurs when people take medicines to deal with illness, or when they choose to work in an occupation that involves routinely dealing with dangerous chemicals. However, most exposures to potentially toxic chemicals are inadvertent, and involve living in an environment that is contaminated with small concentrations of pollutants, for example, those associated with pesticide residues in food, lead from gasoline combustion , or sulfur dioxide and ozone in the urban atmosphere.

Traditionally, the discipline of toxicology has only dealt with the direct effects of poisonous chemicals on organisms, and particularly on humans. Recently, however, ecologists have broadened the scope of toxicological investigations to include the indirect effects of chemicals in the environment, a field known as ecotoxicology. Ecotoxicology could be defined as the study of the ecological effects of toxic chemicals, including the direct effects, but also the indirect consequences caused by changes in the structure of habitats, or in the abundance of food. A herbicide used in forestry may not cause direct, toxic effects to animals at the doses given during the pesticide application, but the pesticide may change the vegetation, and thereby change the ecological conditions upon which animals depend.

Toxicology in practice

The toxicologist employs the tools and methods of science to better understand the consequences of exposure to toxic chemicals. Toxicologists typically assess the relationship between toxic chemicals and environmental health by evaluating such factors as:

• Risk. To assess the risk associated with exposure to a toxic substance, the toxicologist first measures the exposure characteristics and then computes the doses that enter the human body. He or she then compares these numbers to derive an estimate of risk, sometimes based on animal studies. In cases where human data exist for a toxic substance, such as benzene , more straightforward correlations with the humans risk of illness or death are possible.
• Precautionary strategies. Given recommendations from toxicologists, government agencies sometimes decide to regulate a chemical based on limited evidence from animal and human epidemiological studies that the chemical is toxic. Such decisions may have both ethical and political ramifications; to fail to issue warnings about a "suspect" chemical could leave vulnerable members of the population at risk of contracting an avoidable illness; on the other hand, any restrictions placed on the use of the chemical could place burdensome cleanup costs on private industry.
• Clinical data. Some toxicologists devise new techniques and develop new applications of existing methods to monitor changes in the health of individuals exposed to toxic substances. For example, one academic research group in the United States has spent many years developing new methods for monitoring the effects of exposure to oxidants (e.g., free radicals) in healthy and diseased humans.
• Epidemiological evidence. Another way to understand the environmental factors contributing to human illness is to study large populations that have been exposed to substances suspected of being toxic. Scientists then attempt to tie these observations to clinical data. Ecologic studies seek to correlate exposure patterns with a specific outcome. Case-control studies compare groups of persons with a particular illness with similar healthy groups, and seek to identify the degree of exposure required to bring about the illness. Other studies may refine the scope of environmental factor studies, or examine a small group of individuals in which there is a high incidence of a rare disease and a history of exposure to a particular chemical.
• Evidence of bio-accumulation. When a chemical is nonbiodegradable, it may accumulate in biosystems, with the result that very high concentrations may accumulate in animals at the top of food chains. Chlorinated pesticides such as dieldrin and DDT, for example, have been found in fish in much greater concentrations than in the seawater where they swim.

Common toxic materials

Toxicologists have ranked the most commonly encountered toxic chemicals in the United States. In descending order of frequency of encounter, they are as follows:

• Arsenic. Toxic exposure occurs mainly in the workplace, near hazardous waste sites, or in areas with high natural levels. A powerful poison, arsenic can, at high levels of exposure, cause death or illness.
• Lead. Toxic exposure usually results from breathing workplace air or dust, or from eating contaminated foods. Children may be exposed to lead from eating lead-based paint chips, or playing in contaminated soil . Lead damages the nervous system , kidneys, and the immune systems.
• Mercury. Toxic exposure results from breathing contaminated air, ingesting contaminated water and food, and possibly having dental and medical treatments. At high levels, mercury damages the brain , kidneys, and developing fetuses.
• Vinyl chloride. Toxic exposure occurs mainly in the workplace. Breathing high levels of vinyl chloride for short periods can produce dizziness, sleepiness, unconsciousness, and, at very high levels, death. Breathing vinyl chloride for long periods of time can give rise to permanent liver damage, immune reactions, nerve damage, and liver cancer .
• Benzene. Benzene is formed in both natural processes and human activities. Breathing benzene can produce drowsiness, dizziness, and unconsciousness. Long-term exposure affects the bone marrow and can produce anemia and leukemia.
• Polychlorinated biphenyls (PCBs). PCBs are mixtures of chemicals. They are no longer produced in the United States, but remain in the environment. They can irritate the nose and throat, and cause acne and rashes. They have been shown to cause cancer in animal studies.
• Cadmium. Toxic exposure to cadmium occurs mainly in workplaces where cadmium products are made. Other sources of exposure include cigarette smoke and cadmium-contaminated foods. Cadmium can damage the lungs, cause kidney disease, and irritate the digestive tract.

Toxicology and the private citizen

Whenever a group of citizens becomes concerned about the toxicity of a chemical substance, they typically want immediate answers to the following questions:

• Is this chemical harmful?
• At what level of exposure is this chemical harmful?
• What are the symptoms of exposure to this chemical?

Unfortunately, from the point of view of the toxicologist, the answers to these questions are seldom simple. This problem is compounded by the fact that most chemicals of unknown toxicity did not exist until at most a few decades ago, so data for long-term exposure may not exist.

Even when the question is as apparently straightforward, such as "Is such-and-such a chemical harmful?", the answer will seldom be as simple as, "Yes, in amounts exceeding 16 parts per million." This is because a complete scientific answer must take into account other factors such as the age of the individual exposed, the duration of exposure, and whether other environmental pollutants are present that could interact with and magnify the substance's toxicity. In the same way, workplace guidelines for adults who spend an eight-hour day in a factory may be difficult to apply to a residential setting where children and homemakers spend most of their time.

Because modern science and technology developed many of the chemicals scientists are now evaluating for toxicity, it is perhaps not surprising that many laypersons have grown skeptical about the ability of scientists to identify toxic materials. Because toxicologists report their findings in the form of statistics and probabilities, separate government agencies have been known to issue conflicting regulations governing exposure to substances based on different interpretations of the same data.

See also Contamination; Poisons and toxins.

Bill Freedman
Randall Frost