Principles of Toxicology

Toxicology is the study of the harmful effects on living organisms of substances that are foreign to them. The substances of interest include both synthetic chemicals and those that exist naturally in the environment. In toxicology, the effects are normally determined by injecting or feeding animals with the substance of interest and observing how the health of the animal is affected. By contrast, in epidemiology, scientists do not run experiments in a lab but instead determine the health history of a selected group of human beings and attempt to relate differences in disease rates and so on to differences in substances to which they have been accidentally exposed.

Toxicological data concerning the harmfulness of a substance to an organism, such as an organochlorine pesticide or a heavy metal, are gathered most easily by determining its acute toxicity, which is the rapid onset of symptoms—including death at the extreme limit—immediately following the intake of a dose of the substance. For example, experiments show that it takes only a few tenths of 1 microgram of the most acutely toxic synthetic compound—the "dioxin" to be discussed in Chapter 11—to kill most rodents within a few hours after it is administered orally to them.

Although the acute toxicity of a substance is of interest when we are exposed accidentally to pure chemicals, in environmental toxicology we are usually more concerned about chronic (continuous, long-term) exposures at relatively low individual doses of a toxic chemical that is present in the air that we breathe, the water we drink, or the food we eat. Generally speaking, any effects of such continuing exposures are also long-lasting and therefore also classified as chronic.

The same chemical may give rise to both acute and chronic effects in the same organism, although usually by different physiological mechanisms. For example, a symptom of acute toxicity in humans of exposure to many organochlorines is a skin irritation that leads to chloracne, a persistent, disfiguring, and painful analog to common acne, and there is the fear that persistent exposure to much lower individual doses than those which produce the skin disease could eventually lead to cancer.

The three types of substances that produce detrimental effects on human health that are of most concern are

• mutagens, substances that cause mutat ions in DNA, most of which are harmful and can produce inheritable traits if they occur in DNA of cells present in sperm or eggs;

• carcinogens, substances that cause cancer; and

• teratogens, substances in the mother that cause birth defects in the fetus.

Some carcinogens operate in an initiation step, in which the substance— sometimes after itself having been transformed in the body—reacts directly with a strand of DNA. This alteration in DNA can lead to the growth of cancer cells. Others, called promoters, act only after cancer has been initiated, but they speed up the process of tumor formation.

Continue reading here: Dose Response Relationships

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