All you need to know about Toxicology
Toxicology studies the unwanted effects of chemical or physical agents, including drugs and pollutants on living organisms. There are many branches of toxicology, including those that focus on the toxicity of a specific organ system. It is also associated with food safety, metal toxicity, reproductive and developmental toxicology, regulatory toxicology, forensic toxicology, and cancer development. Some of these specialties are described below.
All drugs have the potential to produce unwanted and toxic effects. The scope of undesired effects is broad. Some are only bothersome, like dry mouth, while others are life-threatening. The potential for toxicity is accessed during the development of all new drugs. If the narrow margin exists between an effective dose and a toxic dose, the drug generally requires close monitoring. A blood test may be used to determine if the drug is present at a therapeutic concentration or may be used to assess the effect of the drug on certain targets of toxicity.
Some manifestations of toxicity:
At toxic levels, drugs and other substances can cause cells of a target organ to die. If the insult is severe or prolonged, the organ may not regain normal function. The outcome reflects the ability of the particular organ to regenerate and respond to damage.
The lungs are exposed to many biologically active substances such as asbestos and ozone through inhalation. The bloodstream can also deliver toxic substances to the lung. Certain cancer chemotherapeutic substances can cause lung damage, and the potential for this toxic manifestation has to be weighed against the potential life-saving effects of these drugs. During the repair process, total recovery may be achieved; however, sometimes the damaged cells are replaced by fibrous tissue that does not allow the normal gas exchange processes, intensifying the damage caused by the initial insult.
The liver is a target of many toxic substances. The blood draining the stomach and small intestine are transported directly to the liver, exposing it to high amounts of ingested toxins. The liver provides a protective effect by altering many drugs or ingested toxins, thereby "neutralizing" and/or increasing the removal of these "foreign" substances from the body. In some cases, this process goes awry, and a more toxic substance is produced. For example, with an acetaminophen (Tylenol) overdose, one of the products the liver produces attacks the liver itself and can result in liver failure. The neutralizing substance that normally detoxifies this product and increases its excretion is exhausted in the presence of excessive amounts of the drug. Other drugs can affect the liver through an immune response or by impairing bile flow. The sunlight can convert certain drugs present in the skin to forms that increase the potential for sun burning.
The kidneys are susceptible to the toxic effects of certain drugs in part due to their high blood flow and role as an excretory organ. A large percentage of kidney function must be lost before the impairment causes symptoms or is detected by routine examination.
Examples of non-drug toxins:
Increased incidence of toxicity to chemicals in the environment has increased as the number of chemicals used in everyday life has increased. These chemicals affect not only those that work with them directly but also those who use the products and those exposed to contamination in the air and in the water supply. The Environmental Protection Agency (EPA) oversees the chemical industry, while workers' safety is the focus of the Occupational Safety and Health Administration (OSHA).
Toxic substances present in outside air include carbon monoxide, sulfur dioxide, and nitrogen dioxide. Carbon monoxide impairs the ability of red blood cells to transport oxygen to tissues for respiration. The action of UV light on nitrogen dioxide leads to ozone production that can cause impaired lung function. Sulfur dioxide can also be converted to substances that cause lung damage. Inhalation of particulates such as asbestos and coal dust can likewise cause lung damage. Indoor toxins can result from the use of cleaning products, paints, and solvents in the presence of poor air circulation.
Food additives, metals, and pesticides are other forms of environmental toxins. By normal hand to mouth activity, many children experience lead poisoning through chronic, low-level exposure.
Toxicity involving the immune system:
Toxicity to certain drugs may involve the immune system. The immune system can be impaired (immunosuppression), leading to an increased chance of developing an infection or infrequently, an increased risk of developing cancer. (Sometimes drugs with an immunosuppressant action are intentionally used. An example is in the prevention of rejection in the case of organ transplants.)
The activity of the immune system in response to a drug can also cause tissue damage. Hypersensitivity reactions or drug allergies may be immediate or delayed. The immediate reactions occur quickly after exposure to the offending substance to which the person has been previously sensitized. It may manifest as difficulty breathing, rashes, whelps, increased nasal secretions, and decreases in blood pressure that may proceed to shock. It is thought that some forms of asthma result from an immune response to certain chemicals in the workplace. Other forms of drug hypersensitivity involve the destruction of cells of the circulatory system. It also causes the precipitation of immune complexes in the blood vessels, causing an inflammatory response known as serum sickness. Serum sickness generally manifests as skin eruptions, painful joints, swollen lymph glands, and fever.
Most side effects of drugs do not represent true allergies, and it is important to distinguish the difference. It is possible to adjust the dose of a drug in a non-allergic situation to avoid side effects, but a true allergic response can occur at any dose. Therefore, the drug should never be taken again.
A teratogen is a substance that is capable of causing congenital disabilities in a fetus. The Food and Drug Administration has developed a classification of drugs based on the information available about their safety during pregnancy. Drugs are rated A, B, C, D, or X. Drugs in the A category are considered safe in human pregnancy, and those in the X category have been proven to cause fetal abnormalities. Unfortunately, most drugs have not been adequately tested, and there are few in the A category. Some examples of drugs in the X category are isotretinoin (Accutane) and warfarin.
The forensic toxicologist may also evaluate the presence of drugs or toxins that can modify behavior or performance by analyzing blood, breath, or other specimens. The urine is commonly tested for the presence of drugs and their metabolites as an indicator of prior use or abuse.
In vitro toxicology testing:
There is much interest in developing nontraditional methods to determine drug toxicity. An example of a standard "in vitro" test is the Ames bioassay, in which a chemical shown to be a bacterial mutagen may be further evaluated as a mammalian carcinogen.
Mathematical and computer models can complement animal experimentation by enabling scientists to predict how an organism may respond to exposure at varying levels of a chemical and to design better experiments. Other alternative methods include tissue cultures, transgenic cells and animals, and increased use of invertebrates and non-mammalian species such as fish. The Frog Embryo Teratogenesis Assay-Xenopus (FETAX), for example, can be used to screen chemicals for their potential to cause congenital disabilities. This system can potentially detect growth retardation, structural malformation, and behavioral and functional deficits.