What is toxicology? |

Science and Profession

Since its inception, toxicology has gone through many paradigmatic shifts and has developed several subdisciplines, each with their own approaches and techniques but united by the fundamental challenge of understanding and controlling the interaction between toxic agents and physiological processes. The scale of analysis in which toxicological questions are investigated ranges from molecules to ecosystems, and toxicologists study all kinds of organisms, from the smallest viruses to the largest terrestrial and aquatic organisms.

The popular expression “the dose makes the poison” is one of the key principles of toxicology. It refers to the fact that adverse physiological effects can be produced by practically any substance if given at a dose large enough to overwhelm the body’s natural capacity to process it. Extremely toxic chemicals impart their effects at very small doses. A key measure of toxicity is the lethal dose (LD), which is defined as the amount of a toxic substance that kills an organism. Because the individuals in a group of organisms do not exhibit identical responses, the actual quantitative measure is termed “LD-50,” which is the dose that kills 50 percent of the individuals in an exposed population.

There are three major branches of toxicology: descriptive, mechanistic, and regulatory toxicology. All three branches contribute to risk assessment, which is the main societal application of toxicological knowledge. Mechanistic toxicology is concerned with elucidating the biochemical mechanisms underpinning the expression of toxic effects of poisons at the cellular and/or molecular levels. Assessing the potential toxicity risks associated with new chemicals depends largely on the work of mechanistic toxicologists, who are able to determine whether toxic effects observed in laboratory species are relevant to human exposure levels and physiological attributes. Mechanistic toxicologists also study dose-response relationships that are important for establishing safety thresholds of exposure for industrial chemicals used in manufacturing products and for pharmaceuticals used to treat diseases.

Regulatory toxicology involves the study of how best to protect people from toxic chemicals through the formulation of regulatory policies that govern the manufacture of commercial products, the use and disposal of potentially toxic chemicals, and the protection of workers from toxic exposures at occupational settings. The final responsibility for rejecting or approving specific chemicals for use in commerce rests with regulatory toxicologists, who are trained to evaluate data generated by mechanistic and descriptive toxicologists in light of federal and regional policies designed to protect public and environmental health. Regulatory toxicologists must make judgments following an evaluation of risks associated with short-term exposures and immediate effects (acute toxicity) as well as longer-term exposures and small doses that may result in symptoms long after the initial exposure occurs (chronic toxicity).

Descriptive toxicology forms the bridge between mechanistic and regulatory toxicology. Descriptive toxicologists are responsible for using toxicity testing for comparative risk assessment. For example, the US Food and Drug Administration (FDA) is charged with protecting public health through rigorous evaluation of toxicity levels of drugs and food additives, and descriptive toxicologists employed by the FDA are experts in selecting the best toxicity tests for that purpose. Descriptive toxicologists in the service of the US Environmental Protection Agency (EPA) or the US Department of Agriculture (USDA) collaborate in the comparative toxicity assessment of pesticides used on crops or to control disease vectors. Industrial toxicologists perform similar roles for chemicals used in manufacturing, to minimize adverse impacts on people and the environment.

Toxicologists are usually trained at graduate-level institutions that award master’s or doctorate degrees following specialization in one or more subdisciplines. Clinical toxicology is typically studied and practiced in the hospital setting to quickly recognize the symptoms of toxic exposure, usually in an uncommunicative patient, and to identify the responsible poison, followed by administration of an antidote or other forms of therapy.

Environmental toxicology is the study of the sources, transportation, transformation, and sinks of toxicants in the environment, and how humans come into contact with, and suffer from, exposure to these toxicants. Ecotoxicology is a subspecialty of environmental toxicology that deals strictly with the study of the effects of toxicants on wildlife and ecosystems.

Forensic toxicology is the study of how poisons kill people and how to measure residual levels of poisons in corpses in order to determine the cause and time of death. The practice of forensic toxicology is essential in cases of suicide or homicide involving poisons.

Molecular toxicology is the study of the effects and metabolism of toxic materials in the body at the level of molecules, typically involving molecular genetic analysis and biochemical enzymology. Molecular toxicologists also study how variability in individual genetic characteristics affects human sensitivity to toxic agents, just as age, gender, and body size can all influence human exposure and sensitivity to toxic substances.

Pharmacotoxicology is the study of the toxic effects of pharmaceutical products intended for human or animal consumption. This discipline is aimed at finding the appropriate dose of a chemical that has a healing effect without overwhelmingly toxic side effects.

Most practicing toxicologists belong to the professional Society of Toxicology, an organization that defines the responsibilities of toxicologists. The first is to develop new and improved ways of determining the potentially harmful effects of chemical and physical agents and the dose that will cause these effects. This responsibility requires a thorough understanding of the molecular, biochemical, and cellular processes responsible for diseases caused by exposure to toxic substances. The second responsibility is to study commercial chemicals and products using carefully designed and controlled empirical analyses and modeling to determine the conditions under which they can be used with minimum or no adverse effects on human health, wildlife, and ecosystems. The third is to conduct toxicological risk assessments, including estimating the probability that specific chemicals or processes pose significant risks to human health and/or the environment. The risk assessments form the basis for establishing rules and regulations that underpin government policies designed to protect public health and the environment.

Diagnostic and Treatment Techniques

The diagnostic and treatment techniques used by toxicologists depend largely on the branch of toxicology in which they practice. For example, clinical toxicologists in the hospital setting must be proficient at rapid diagnostic techniques for implementing emergency response to acute exposure to poisons. According to data published by the American Association of Poison Control Centers (AAPCC), which operates the National Poison Data System, 10,830 calls are made to poison centers in the United States each day; these poison response centers deal with a new poisoning case approximately every thirteen seconds. The AAPCC reported that US poison response centers received more than 3.1 million calls in 2013.

More than half of all poisoning cases occur in children younger than six years of age, although these incidents are rarely fatal. A major challenge for toxicologists is to quickly diagnose poisoning events in children who typically may not have the vocabulary or level of consciousness to describe the exposure event to their caregivers or to the emergency response staff when they are brought to the hospital. Most poisonings occur in the home from domestic items such as cosmetics and personal care products, cleaning fluids, medications, and pest control chemicals. Therefore, the first step in diagnosis is to identify as precisely as possible the specific chemical(s) that caused the poisoning; this can most easily be achieved through perusing the list of ingredients on the suspected container but is not always possible. It is more difficult if the poison is gaseous with a remote source. Therefore, body fluid samples (saliva, urine, or blood) can be tested using rapid techniques to identify major categories of common poisons, their known physiological effects, or biomarkers of exposure.

Application of first aid techniques is the first line of treatment for poisonings after ensuring that the patient is removed completely from the source of exposure. Follow-up treatment of poisoned patients involves three major steps. The first is to facilitate the elimination of ingested or injected poison from the body. Stomach pumping is sometimes effective for ingested poisons if applied within a time frame that occurs before a fatal dose is absorbed in the stomach. Typically, in a gastric lavage process, a siphon tube is inserted into the stomach through the mouth to repeatedly flush and empty the contents.

The second step is the application of effective antidotes that aid the excretion or inactivation of the poison either through natural liver functions or through specific biochemical reactions. Activated charcoal may be given, preferably to conscious patients through the mouth, for the purpose of absorbing the poison, thereby reducing the biologically available dose. In serious situations in which poisons are injected into the bloodstream or when poisons have been absorbed extensively from the stomach or lungs, hemodialysis may be performed to filter the blood directly through the use of artificial kidneys. Where artificial kidneys are not available, charcoal may be used for blood filtration (hemoperfusion). For poisoned patients exhibiting respiratory distress, breathing support through ventilators is an essential treatment strategy.

The third step is the treating of symptoms and the aiding of recovery. Depending on the nature of the poison, treatment may involve controlling seizures, correction of irregular heartbeat, regulation of blood pressure, and repair or replacement of damaged organs, including the kidneys and liver.

Posttreatment counseling is recommended to prevent further poison exposures through educational programs, drug rehabilitation, or mental health referrals in cases of suicide attempts. Poisoning cases may also involve substantial legal proceedings for forensic toxicologists or in cases of potential homicide.

Perspective and Prospects

Poisons and their effects on human health have been known since antiquity, but the scientific study of poisons and systematic information on their synthesis and mode of action is a relatively recent development. The German scientist Auroleus Phillipus Theostratus Bombastus von Hohenheim (1493–1541), popularly known as Paracelsus, is considered by many to be the world’s first authority on and founder of toxicology as a scientific discipline. Among his several notable accomplishments, Paracelsus is credited with introducing the use of mercury and arsenic into medical practice for curative purposes. Furthermore, he is the source of the famously paraphrased maxim “the dose makes the poison.” His exact statement in German translates as, “All things are poison and nothing is without poison; only the dose makes a thing not be poison.”

Toxicology is a rapidly evolving specialty, driven by innovations in chemical manufacturing and the growing number of toxic substances accessible to the general population. Progress in toxicology is also driven by discoveries in human genomics and proteomics. The more that is learned about the variability in the nucleotide sequences of individuals in a population, the better understood are the differences in human response to toxic chemicals. Additional work in mechanistic toxicology and descriptive toxicology remains to be done to understand adequately the interactions among genetics, age, gender, body size, and behavioral traits that mediate human exposure and response to poisons. Furthermore, the human body is exposed to a large number of chemicals on a daily basis. Very little is known about how these chemicals interact to make people more or less vulnerable to the toxic effects of poisons.

It is important to create a seamless strategy for translating laboratory data, including those based on animal or microbial model systems, into regulatory policies designed to protect the most vulnerable members of society. It is also important to create a seamless strategy for understanding the interactions of toxic chemicals in ecosystems and how these interactions influence human vulnerability and sensitivity to toxic exposures at the workplace, on the streets, and at home. Finally, toxicology has been neglected for too long by the engineering professions that create the products upon which society relies. Toxicology must be engaged as much as possible in the product design stage, before large-scale manufacturing of consumer products that end up endangering the public and ecosystems through the expression of toxicity at various stages of the product life cycle.

Bibliography

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