Toxicology, Specialty Areas

Broadly speaking, poisons are substances that cause harmful effects when they are introduced to living organisms. Toxicology is the systematic study of poisons. There are many different ways in which toxicology can be approached.

Interest in poisons, and their practical relevance to humans, goes back to antiquity. No doubt the earliest of humans recognized the effects of poisons in the form of animal venom or poisonous plants. Many poisons were included in the medical writings of ancient Egypt in the Ebers Papyrus (the oldest preserved medical document, written about 1552 b.c.), and by the time Greek culture had risen to prominence, the systematic study of poisons and their uses in everyday life had become fairly well developed. It was common practice throughout the ages for rulers and leaders to employ a cupbearer to taste their wine and food to avert threats of poisonings. Focus on toxicology has increased in recent years because of concerns for environmental pollutants and worries over toxic food additives. This resulted in the creation of the Environmental Protection Agency in 1970, and the Toxic Substances Control Act in 1976, which requires all uses of new chemicals be reported to the EPA prior to their use.

Forensic toxicology is a combination of analytical chemistry and general principles of toxicology. This is a branch of medicine that focuses on medical evidence of poisoning, and tries to establish the extent to which poisons were involved in human deaths. Forensic toxicology is in many ways a kind of detective work that assembles the subtle clues found in the tissues of the body during autopsy .

Clinical toxicology is the study of diseases and disease states caused by exposure to toxins . This differs from forensic toxicology in that it is most often a study of the living, rather than only the dead. It often involves a study of toxicokinetics, the study of how the levels of toxicants and their metabolites change over time, the time that it takes to eliminate toxicants after exposure, and ways in which the toxic effects of various poisons can be reduced in persons who have been exposed, or how elimination of the toxicant can be increased.

Descriptive toxicology is concerned directly with toxicity testing. In descriptive toxicology, the toxic properties of chemical agents are systematically studied for various endpoints using a variety of different organisms. At what point does a chemical agent cause death to 50% of the animals under study? To what extent are various agents irritating to the eyes? How frequent are birth defects in the offspring when mothers are exposed during pregnancy? Descriptive toxicology is an attempt to characterize the toxic potential of various agents in a wide array of systems.

Mechanistic toxicology is the study of the many mechanisms by which toxins exert their effects on living systems. This is the identification of the targets to which toxins may bind, the tracking of the toxin as it is absorbed and distributed throughout the body, and the process as it is metabolized and altered by the body. This includes study of the stepwise manner in which toxicants enter the system, find their targets, and make incremental changes on the natural system. Mechanistic toxicology also involves the study of how these agents are metabolized and excreted after exposure has occurred.

Regulatory toxicology is the translation of laboratory testing data into policies concerning the applications and uses of chemicals in society, and the limits of allowable exposure in various settings. The regulatory toxicologist compares the toxicity profile with other known toxicants and tries to establish standards for allowable limits that are consistent with other agents with similar effects. Regulatory toxicology is the primary basis for laws that limit exposures for people and for the environment.

Biochemical toxicology is the study of the interactions toxicants have within living systems. Many of the aspects of mechanistic toxicology are found in the study of biochemical toxicology. What are the portals of entry into the living system? How is the agent distributed and metabolized once it is taken in? How does toxicity vary by age, sex, diet, and during pregnancy? What are the sites of action of the toxicant? How is the toxicant eventually metabolized and eliminated?

It wasn't very long ago that lakes, rivers, and oceans were considered to be a nearly infinite in size; the atmosphere an infinitely large reservoir of air; and the ground a nearly endless reserve for solids. Consequently, wastes from manufacturing or daily living were dumped into the ocean, released through smokestacks into the air, or buried into landfills without concern for the long-term consequences. Rachel Carson's book Silent Spring, published in 1962, served as a powerful warning that continuing these practices would lead to a progressive erosion of many different ecosystems. The area of environmental toxicology arose to a high level of social concern for the study of the impact of toxic agents on the environment, and the fate of toxicants released into various ecosystems.

Pollutants in the air that can have sweeping consequences in human health and in various ecosystems have been long recognized as a problem in society. Environmental toxicology studies of the air can include the types and sources of airborne pollutants, acute and chronic health effects of various pollutants in the air, transport of particulate and gaseous pollutants in air, changes in the ozone layer resulting from natural and man-made pollutants, chemical and photochemical transformations and reactions, and monitoring of toxicant levels over time. Similarly, environmental toxicology studies of soil and water follow many of the same kinds of issues and problems seen with air pollutants.

Teratology is the study of the effect of toxicants on the developing embryo when the mother is exposed during pregnancy. Teratogens are agents that are capable of causing birth defects when exposure occurs during pregnancy. Embryonic and fetal growth and development begins at the time of conception, and continues on for a period of approximately 9 months. This is a time of remarkable growth, and a unique period of development of body tissues, organs, and structures.

For teratogens, the timing of exposure is a key consideration. The two-week period from conception until implantation into the uterus is generally regarded as an all-or-none period where toxins will either cause pregnancy failure altogether, or have no effect at all. As pregnancy proceeds from this point, many changes are taking place. The embryo starts off as a single cell, but very quickly grows and becomes highly organized, first with the development of specific tissues, followed by development of many different organs and body structures. Toxins that might not be very harmful in adults or children could disrupt these unique events during embryonic or fetal development. Because the various stages of development are carefully timed, it becomes essential to know the timing of exposures to various potential teratogens in assessing their safety. As in most other areas of toxicology, the amount of the toxicant reaching the target tissue is another important variable. As prescription drug exposures are fairly well defined both for dose and for timing, most of the reliable data on potential teratogens is associated with prescription drug use. Illicit drugs , and other environmental exposures are harder to track, and it is often difficult to establish the safety or risk associated with these kinds of agents. True teratogens generally leave a distinctive pattern of specific birth defects following exposure at a specified critical time during pregnancy. Exposures at times outside of the critical time period often have no toxic effects on the developing baby.

Genetic toxicology is the study of the effects of chemicals and other environmental agents that can cause mutations or cancer. Agents that cause cancer are called carcinogens, and those that cause genetic mutations are called mutagens. Agents that causechromosome breaks and rearrangements are called clastogens.

The Delaney Clause prohibits the use of any chemical intended for use in food in the United States that is found to induce cancer when ingested by humans or animals. Every new chemical that is proposed for use in foodstuffs therefore undergoes extensive testing to evaluate its carcinogenic potential, and all drugs and candidate drugs are subjected to similar scrutiny.

There are a number of approaches used to investigate the carcinogenic potential of chemicals. One method is to expose laboratory animals such as mice, rats, or dogs to a range of doses of a drug or chemical for the duration of their lives, and to compare their rates of cancer with control animals that are not exposed. A true carcinogen will generally show a significant difference in cancer rates between animals that are exposed compared with those that are not, and usually there is a higher rate of cancer in animals receiving higher doses compared with those receiving lower doses.

Other tests for cancer causing potential are focused on cells grown in culture. In these tests, the endpoint is usually not cancer, but some other physiological or biochemical change known to be associated with cancer such as breaks in DNA , chemical modifications of DNA, or a wide variety of other biochemical changes. Testing, such as the Ames test, may involve bacterial cells. Yeast, insect, rodent, and human cells may be utilized in different assays. These tests are relatively inexpensive compared to long-term animal exposure studies. Most often these tests are used to screen for carcinogens to avoid long-term whole animal studies, or are used to support the apparent safety of agents that test negative in long-term studies.

see also Air and water purity; Animal evidence; Botulinum toxin; Death, cause of; FDA (United States Food and Drug Administration); Toxicological analysis; Toxins.