toxicology

The study of the nature, effects, and detection of poisons and the treatment of poisoning.

The study of the adverse effects of chemical and physical agents on living organisms. Toxicology has also been referred to as the science of poisons. See also Environmental toxicology; Poison.

The most important factor that influences the toxic effect of a specific chemical is the dose. All chemicals, including essential substances such as oxygen and water, produce toxic effects when administered in large enough doses. Another significant factor is the route of exposure. Living organisms may be exposed to a chemical by inhalation (into the lungs), ingestion (into the stomach), penetration through the skin, or, in special circumstances, injection into the body. In general, substances are absorbed into the body most efficiently through the lungs so that inhalation is often the most serious route of exposure.

A third factor is the fate of the chemical after the organism is exposed. The chemical may not be absorbed at all, limiting its possible adverse effects to the site of exposure. If it is absorbed, then it may travel throughout the body and has the potential to cause toxic effects at one or more sites remote from the site of entry. The remote sites where these adverse effects occur are called target organs.

Another significant variable is the time course of the exposure. A quantity of chemical administered at one time may have an effect even though the same quantity administered in small doses over time has no effect.

In view of the importance of timing in producing adverse effects, toxicologists distinguish between two broad classes of toxicity, acute and chronic. Acute toxicity refers to effects that occur shortly after a single exposure or small number of closely spaced exposures. Chronic toxicity refers to delayed effects that occur after long-term repeated exposures.

Traditionally, the effect of most concern for acute toxicants (such as cyanide) is death. Acute toxicity is generally measured by using an assay to determine the lethal dose; rodents are given single doses and the number that have died 14 days later is recorded. The data are plotted for each dose, and the dose that is lethal for 50% of the animals (lethal dose 50 or LD₅₀) is used as the criterion for acute toxicity. See also Lethal dose 50.

Some synthetic chemicals, such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT), exhibit their effects only after a number of repeated exposures and are considered chronic hazards, with cancer and reproductive effects being of greatest concern. To determine the dose at which chronic effects occur, rodents are exposed to daily doses of the chemical under study for long periods of time—from a few months to a lifetime. The highest dose at which no effects can be observed, the no observed effect level (NOEL), is used as a measure of chronic toxicity. See also Mutagens and carcinogens.

Toxicology is essentially the science of poisons. It was recognized long ago that the toxicity of any substance is related to dose. The sixteenth-century iconoclast Paracelsus is credited with the statement: ‘All substances are poisons, there is none which is not a poison. The right dose differentiates a poison from a remedy.’ Toxicology had its origins in medicine and therapeutics, and to this day one of the key steps in the development of new drugs is the evaluation of the ‘therapeutic window’. This window corresponds to the range of doses where a beneficial effect is obtained but below the dose which causes unacceptable side-effects.

Throughout history the substances that have been used for medicine — as well as the poisons used to eliminate political rivals, as practised from classical times through to the Renaissance — have been almost exclusively derived from natural sources. Despite a recent emphasis on the toxicity of synthetic chemicals, arising in part from the influential writings of Rachel Carson, it is interesting to note that Nature has been endlessly inventive in its production of toxic agents. Such natural toxic substances are sometimes used as part of defence mechanisms as, for example, in the case of snake venoms. However, sometimes the toxic substances are by-products of normal metabolism by many different species. Several varieties of the mould Aspergillus produce a group of carcinogens called aflatoxins, which cause liver injury and cancer. A proper understanding of the occurrence and actions of natural toxins is vital to the maintenance of a healthy lifestyle. In a number of countries cassava is a major source of carbohydrate, but if it is not properly treated ingestion of the naturally occurring cyanogenic (cyanide-forming) glycosides can be fatal.

From the mid nineteenth century onwards the increasing use of pure chemicals as drugs paved the way for the development of toxicology as a more exact science which aimed to unravel the mechanisms of action of toxic substances. Very few drugs or toxic agents are active without some sort of metabolic activation; a chemical or physical change brought about in the body. Usually the effect of these changes is to render the substance more water soluble so that it may be excreted as rapidly as possible. In some instances metabolism results in the formation of a reactive chemical species, which binds to cellular macromolecules such as DNA or proteins. Such modifications can then lead to biological consequences, which are manifested as a frank toxic effect. However, there are protective mechanisms for dealing with such reactive species within cells; many are converted into substances that are ultimately excreted in urine.

In some cases unfortunate toxicological incidents can have beneficial consequences in the long term. For example, it was noted that soldiers returning from World War I who had been exposed to sulphur mustard had very depressed white blood cell counts. Ultimately, this observation led to the development of nitrogen mustards which, soon after World War II, began to be widely used in the treatment of cancers such as leukaemia. A rather different story relates to the discovery of a class of potent carcinogens, the nitrosamines. Several poisoning incidents in the textile industry, starting in the late 1930s, were associated with the use of dimethylnitrosamine (DMN) as a solvent for rayon. It was shown in animal models that acute administration of DMN produced a characteristic type of liver damage similar to that seen in workers. However, chronic administration of low doses of DMN produced liver tumours. It was subsequently found that many other nitrosocompounds produced tumours in different organs in many species of animals. Paradoxically, some nitrosocompounds were found to have antitumour activity and, like the nitrogen mustards described above, probably act by damaging the DNA in tumours in such a way that the cells cannot repair the damage and die.

There are sometimes great differences between species and between individuals with regard to the toxicity of a particular substance. A famous example is penicillin, which was tested for toxicity in rats before being given to humans. As rats tolerated large doses of penicillin with no ill effect, the drug was considered safe enough to be administered to humans, and the age of antibiotics was born. It was subsequently found that guinea pigs are very susceptible to toxicity from penicillin — history might have been very different if guinea pigs had been the test animal of choice. For many drugs which require metabolism to be active, or, in some cases, for toxicity to be apparent, polymorphism (occurrence in more than one form) of key metabolic enzymes can lead to spectacular differences in individual susceptibility. Debrisoquine, a drug used in the treatment of high blood pressure, was found to be very slowly metabolized by 1 in 10 Caucasian people, due to a genetic polymorphism for a particular enzyme. In affected individuals, administration of the drug caused a dramatic fall in blood pressure due to the persistence of the active drug in the circulation.

Despite much current public concern about health effects from environmental chemicals, there is little or no evidence of large numbers of cases of any disease being due to exposure to such agents. It is not that chemicals are any more or less toxic than those to which earlier generations were exposed — it is rather that contemporary exposure levels have been progressively reduced to such an extent that effects are almost undetectable. As our understanding of the mechanisms of toxicity of chemicals has improved, it is less likely that highly dangerous industrial chemicals will be present in the environment. However, as indicated above, our exposure to natural toxic agents remains a major source of concern.

Over much of its history the study of toxicology has relied upon the manifestation of some adverse health effect, in either humans or experimental animals, as an indication of the toxic effects of any particular substance. As the Human Genome Project attains one of its first goals of obtaining the complete sequence of the human genome (and as the complete sequences of the genomes of many other species have either already been, or will shortly be, completed), it is likely that approaches to toxicological questions will be quite different in the near future. Many pharmaceutical companies have led the way in the exploitation of this technology for rapid and comprehensive screening of adverse side effects of the increasing numbers of novel substances that are being examined for beneficial effects.

— David Shuker

Bibliography

• Klassen, C. D. (1996). Casarett and Doull's Toxicology: the basic science of poisons. McGraw Hill, New York.
• Timbrell, J. A. (1991). Principles of biochemical toxicology, (2nd edn). Taylor and Francis, London

See also drug; environmental toxicology; poisoning.

A person versed in toxicology.

Toxicology is the science of poisons. Understanding the potential for toxicity of agents found in nature has been a necessity for human survival. Learning to use natural toxins for purposes such as hunting and warfare was as much a part of human adaptation of the environment as was the taming of fire. One of the first known examples of the unwanted toxicity of a manufactured product was the lead poisoning that occurred in Roman times as a result of lead plumbing and lead dishware. Today, the emphasis of toxicology is on detecting and preventing the unwanted effects of chemical and physical agents, although concerns about the intentional misuse of chemicals, including chemical warfare, will persist for the foreseeable future.

As a science, toxicology is at the interface between chemistry and biology. There are three "laws" of toxicology. The oldest, that "the dose makes the poison," is attributed to Paracelsus, a fifteenth-century German physician. The concept that all chemical agents are toxic at some dose is central to a respect for the inherent hazard of all chemicals. The second "law" of toxicology, that the biologic actions of chemicals are specific to each chemical, has been attributed to Ambroise Paré, a sixteenth-century French surgeon who recognized that toxic agents have different effects dependent upon their inherent nature. Understanding the specific action of chemicals, known as hazard identification, depends upon recognizing the structural determinants of the activity of chemicals, and the biological niches in which chemicals interact. Very subtle changes in chemical structure can make an enormous difference in biological effects. The third "law" is that humans are animals. Protection against the toxicity of chemicals today would be impossible without the ability to study the effects of toxic agents in laboratory animals. As a corollary, animal rights activists advocating a ban on all animal research present a major threat to environmental protection and public health.

Toxicologists generally consider two types of dose-response relationships. One has a threshold below which no effect is expected. For example, one drop of fuming sulfuric acid will burn a hole in skin, yet this same drop in a bathtub full of water dilutes the sulfuric acid to a level at which no effects will occur. This theoretical threshold (experimentally known as a "no-observed-effect level") is presumed to exist for all agents, except for those that produce their effects through mutation, most notably many cancer-causing agents. A mutation can theoretically occur through a single chemical molecule producing a specific change in the chemical structure of a DNA molecule, thereby altering the genetic code from that of a normal cell to that of a mutated cell. As a further simplification, two molecules have twice as much chance as causing this effect. This can be described as a linear one-hit relationship between the dose of a mutational agent and the likelihood that the mutation will occur. The theoretical risk for any one molecule causing a mutation is infinitely small—there are about 1 trillion molecules of benzene, a known cause of leukemia, in every breath taken in an average American city, yet very few people develop leukemia. There are also many defense mechanisms within cells, as well as DNA repair mechanisms, that can impact on the likelihood of chemical exposures causing cancer.

Extrapolation of data from laboratory animals to humans, and from high to low doses, is central to modern toxicology. In addition to understanding dose-response relationships, knowledge about differences among species in the uptake, metabolism, and disposition of chemicals is also of importance. There is a strong similarity among mammalian species. Where differences do exist, attention to the kinetics of the processes that determine how an external exposure level is translated to the dose of a chemical at a target organ provides information of value to cross-species extrapolation.

A major challenge in modern toxicology is to prevent unwanted effects of otherwise valuable chemicals, including therapeutic agents. Understanding chemical mutagenesis and carcinogenesis has permitted the development of bacterial mutagenesis assays, such as the Ames test. These and other short-term assays for toxic effects are routinely used during the development phase of new chemicals to screen out potential toxic agents. Before marketing, additional testing is often required, depending in part on the use of the chemical. For new pharmaceutical agents, extensive toxicity and efficacy data are required, including studies in humans. Such agents are expected, at anticipated human dose levels, to have a biological effect of benefit to the consumer. In contrast, the developers of consumer chemicals, such as a new paint, hope that no biological effects will occur at usual doses to humans.

There are intermediate agents, such as insecticides and herbicides, for which a biological effect is intended at usual doses—for these agents, protection of humans depends, in large part, on our different biology. Accordingly, premarket testing is usually less rigorous for consumer chemicals than for therapeutic agents, and there is more dependence on structure-activity relationships (SAR). SAR, in essence, is a comparative analysis of aspects of chemical structure in relation to the existing toxicological database—a useful, but not completely effective, approach. In the United States, the Toxic Substances Control Act requires premanufacturing notification of new chemicals to the U.S. Environmental Protection Agency, which has the option of asking for additional testing. Such tests might include a battery of shorter-term and longer-term tests for acute and chronic diseases, including cancer. The recognition of the dangers inherent in compounds that bioaccumulate or otherwise persist in the environment has led to tests to identify and exclude such compounds from commerce.

Long-term animal assays, usually two-year studies in male and female rats and mice, are the mainstay of thorough safety assessment of chemicals, particularly those for which there is a concern about cancer or other chronic effects. The basic approach is to first perform a multiple-dose ninety-day study to choose the maximum tolerated dose (MTD). This dose is then used for a two-year study. Sole reliance on standard safety-assessment approaches carries a small but finite risk of missing a potentially toxic agent, a risk which is lessened if studies assessing the mechanism of toxicity of the chemical are also performed. A major goal of toxicological research is a better understanding of the processes by which chemical agents produce adverse biological effects, which will lead to the development of better safety-assessment tests.

The pathways of chemicals into and through the body are usually considered under the headings of absorption, distribution, metabolism, and excretion. Absorption, the process by which an external dose is converted to an internal dose, occurs by ingestion, inhalation, or through the skin. Distribution of a chemical depends in part on the pathway of entry and on specific chemical and biological factors; for example, only certain types of chemicals are able to penetrate the blood-brain barrier and enter the central nervous system.

Much emphasis has been placed on understanding chemical metabolism, as this is central both to the impact and to the detoxification of chemicals. The activity of many of the metabolic enzymes can vary greatly among individuals due to genetic and environmental factors, including types of food. Further, metabolic rates may vary within a given individual at different times due to induction of metabolic enzymes by these same environmental factors. Studies of resistance to cancer chemotherapeutic agents have led to an understanding of mechanisms by which toxic agents can be rapidly transported out of an otherwise susceptible cell, including specific transporter proteins, which can also be induced in response to environmental factors.

The major metabolic organ is the liver, but all organs have some level of metabolic enzymes. Certain chemicals, such as benzene, are harmless until they are metabolized by the body to form toxic chemical intermediates. Further, not all chemicals are metabolized; some pass through the body unchanged, while others react directly with biological targets.

Major excretory pathways are through urination, defecation, and exhalation. Lactation is also a means of excretion, particularly of fat-soluble chemicals, to the potential detriment of the infant.

Differential sensitivity to chemicals is an important subject to toxicologists for which modern molecular biology is providing new insights, particularly through the understanding of the human genome. For most human disease, genetics will determine what is necessary, but the environment, defined broadly, will determine what is sufficient. A reasonable estimate is that over two-thirds of human disease is environmentally determined. Many of the genetic and environmental factors responsible for disease operate at the level of modifying the absorption, distribution, metabolism, or excretion of exogenous chemicals, including food constituents.

Susceptibility to toxic agents is also conferred by factors such as age, gender, and concomitant conditions. Children, the elderly, and those with preexisting disease tend to be more susceptible to environmental toxins than are healthy adults. For example, the greater respiratory ventilation per unit of body mass in children accounts for the tragic finding of death due to carbon monoxide poisoning in the children, but not the adults, in a snowbound car.

So-called safety factors have traditionally been used in establishing public health and regulatory guidelines and standards based on toxicological data. These are based on no-observed-effect levels in animals, which are then reduced by a factor of ten to provide assurance that the animal data is protective of humans. In general, a tenfold factor is used to account for the possibility that humans are more sensitive than the animal species from which the data are obtained. Another tenfold factor is based on the greater diversity in susceptibility factors among humans than in inbred laboratory animals. The resultant hundredfold safety level has been used on a relatively routine basis for establishing acceptable daily intake (ADI) levels by the Food and Drug Administration, as well as for other regulatory standards. Additional factors of ten can be added based upon the toxic endpoint involved, or in order to protect children. Conversely, when there is a sufficiently robust database on humans, such as for certain air pollutants, routine factors of ten are not used, and scientific judgment contributes to the determination of an appropriate margin of safety.

The effect of toxic agents on ecosystems has become increasingly recognized as being important to human health. Traditionally, ecotoxicology (in relation to human health) has focused on contamination of the food chain, including the biomagnification and bioaccumulation of toxic agents within foods. The recognition of the role of ecosystems in overall planetary health, including feedback loops affecting climate, desertification, and crop yield, as well as the importance of the natural world and its animal and plant components to human well-being, has led to additional emphasis on understanding the toxicity of chemical and physical agents to components of nature.

(SEE ALSO: Ames Test; Benzene; Carcinogenesis; Ecosystems; Environmental Determinants of Health;Environmental Protection Agency; Ethics of Public Health; Genes; Genetics and Health; Lead; Maximum Tolerated Dose; One-Hit Model; Risk Assessment, Risk Management; Safety Assessment; Safety Factors; Threshold)

Bibliography

Goldstein, B. D., and Henifin, M. S. (2000). "Reference Guide on Toxicology." In Reference Manual on Scientific Evidence, 2nd edition. Washington, DC: Federal Judicial Center.

Klaassen, C. D., ed. (1996). Casarett and Doull's Toxicology: The Basic Science of Poisons, 5th edition. New York: McGraw-Hill.

Lippman, M., ed. (1999). Environmental Toxicants: Human Exposures and Their Health Effects, 2nd edition. New York: John Wiley.

— BERNARD D. GOLDSTEIN

For more information on toxicology, visit Britannica.com.

The science of toxicology is concerned with the adverse effects of chemicals on biological systems and includes the study of the detection, action and counteractions of poisons. Toxicologists today generally use the techniques of analytical chemistry to detect and identify foreign chemicals in the body, with a particular emphasis on toxic or hazardous substances. Toxins can be simple metal ions or more complex, inorganic and organic chemicals, as well as compounds derived from bacteria or fungi and animal-produced substances such as venoms. Poisons can range in their effects from a low-level debilitation to almost immediate death. Many drugs used to counter diseases can also be poisons at higher concentrations.

One of the most significant historical figures in the development of the science of toxicology was the Swiss physician and alchemist Paracelsus (1493–1541). He realized that there was a need for proper experimentation in the field of chemical therapeutics and distinguished between the therapeutic and toxic properties of substances, recognizing that they are indistinguishable except by dose. Paracelsus realized that it is not possible to categorize chemicals as either safe or toxic and laid the foundations for a key principle in toxicology known as the dose-response relationship. There is a graded dose-response relationship in individuals and a quantal dose-response relationship in a population. The quantal "all or none" dose-response is used to determine the median lethal dose (LDm), which estimates what percentage of the population, would be affected by a dose increase. Estimation of LDm involves the use of at least two different animal species and doses of the chemical under test are administered by at least two different routes. Initially most of the test animals die within 14 days. Subacute exposure is then tested for a period of 90 days and long-term exposure testing takes a further 6 months to 2 years. Mathematical extrapolation is used to generalize results from animal testing to human risk incidence.

Another significant figure in toxicology was Spanish physician Orfila (1787–1853) who contributed to the specialty known as forensic toxicology. He devised methods of detecting poisonous substances and therefore provided the means of proving when criminal poisoning had taken place. After Orfila, toxicology developed further to include the study of mechanisms of poison action.

Forensic toxicology involves the use of toxicological methods for legal purposes. There is a considerable overlap between forensic and clinical toxicology, criminology, forensic psychology, drug testing, environmental toxicology, pathology, pharmacology, sports medicine and veterinary toxicology. The work of a forensic toxicologist generally falls into three main categories: identification of drugs such as heroin, cocaine, cannabis; detection of drugs and poisons in body fluids, tissues and organs; and measuring of alcohol in blood or urine samples. Results of the laboratory procedures must then be interpreted and presented to the legal courts.

A forensic toxicologist is normally given preserved samples of body fluids, stomach contents, and organ parts along with a coroner's report containing information on symptoms and postmortem data. Specimens are generally divided into acidic and basic fractions for drug extraction from tissue or fluid. As an example, most of the barbiturate drugs are acid-soluble while most of the amphetamine drugs are base-soluble. After preliminary acidbase procedures, tissue or fluid samples are subjected to further laboratory tests consisting of screening tests and confirmation testing. Screening tests allow the processing of many specimens for a wide range of toxins in a short time and any positive indications from the screens are then verified with a confirmation test.

Laboratory methods used in toxicological analysis are various. Screening tests include (1) physical tests: testing the boiling point, melting point, density, and refractive index of a substance; (2) crystal tests: treatment of a substance with a chemical reagent to produce crystals; (3) chemical spot tests: treatment with a chemical reagent producing color changes; (4) chromatographic tests (thin layer or gas): these separate the mixtures under investigation. Confirmatory tests generally involve mass spectrometry in combination with gas chromatography. Every toxin has a characteristic mass spectrum that identifies it absolutely.

Drugs analysis in tissue samples can be very complicated and a substance under analysis must be subjected to rigorous tests with no margin for error. A range of screening tests employing color reactions exist for the detection of illegal drugs. Some commonly used color tests include the Marquis test for opium, Duqunois-Levine test for Marijuana, Van Urk test for LSD, Scott test for cocaine, and Dillie-Koppanyi test for barbiturates.

The challenges of modern science call on clinical and forensic toxicologists to expand their services. They are now encouraged to engage in research and development to meet a number of changing needs. Modern molecular biology has opened up a number of interesting possibilities for toxicologists. For example, genotyping for interpretation of potential toxic drug interactions and criminality testing is becoming a field of great interest. With the emergence of pharmacogenetics, genotyping may enhance rational drug therapy for better patient care, and may explain unexpected adverse or fatal drug reactions in postmortem analysis.

Expanding responsibilities for forensic toxicologists also derive from the greater threat of terrorism. Terrorism via weapons of mass destruction has moved out from war zones to civilian settings. Modern terrorist weapons may be in the form of nuclear, biological, and chemical devices. Recently, the possible use of chemical or biological weapons in the Middle East conflicts, the use of sarin gas in a Tokyo subway station, and the unregulated availability of nuclear fuel in some countries have all heightened the potential risks. Toxicologists must now be knowledgeable about the clinical pharmacology, safe samples processing, and possible screening and/or analysis of substances such as vesicants, cyanide, nerve agents, and riot control agents.

Further Reading

Books

Bodziak, J., and Jon J. Nordby. Forensic Science: An Introduction to Scientific and Investigative Techniques. CRC Press, 2002.

Klaassen, C. D. Toxicology: The Basic Science of Poisons. McGraw-Hill Companies, 2001.

Periodicals

Goldberger, B. A., and A. Polettini. "Forensic Toxicology: Web Resources." Toxicology 173 (2002): 97–102.

Maurer H. H. "Liquid Chromatography-mass Spectrometry in Forensic and Clinical Toxicology." J Chromatogr B Biomed Sci Appl. 713 (1998): 3–25.

Richardson T. "Pitfalls in Forensic Toxicology."Ann Clin Biochem. 37 (2000): 20–44.

Thormann, W., Y Aebi, M. Lanz, and J. Caslavska "Capillary Electrophoresis in Clinical Toxicology." Forensic Sci Int. 92 (1998): 157–83.

Wong, S. H. "Challenges of toxicology for the millennium." Ther Drug Monit. 22 (2000): 52–7102.

A specialist in toxicology.

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Toxicology and Poison

General Toxicology (Forensic) Toxinology History of poison

Concepts Poison Venom Toxicant (Toxin) Acceptable daily intake Acute toxicity Bioaccumulation Biomagnification Fixed Dose Procedure LD50 Lethal dose Toxic capacity Toxicity Class

Treatments Antidote Gastric lavage Whole bowel irrigation Activated carbon Cathartic Hemodialysis Chelation therapy Hemoperfusion

Incidents Bradford Minamata Niigata Alexander Litvinenko Bhopal 2007 pet food recalls Seveso disaster List of poisonings

Related topics Hazard symbol Carcinogen Mutagen List of Extremely Hazardous Substances Biological warfare Food safety

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Toxicology (from the Greek words toxicos and logos) is the study of the adverse effects of chemicals on living organisms.^[1] It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people.

Contents 1 History 2 Relationship between dose and toxicity 3 Toxicity of metabolites 4 Subdisciplines of toxicology 5 Chemical toxicology 6 See also 7 References 8 Further reading 9 External links

History

See also: History of poison

Mathieu Orfila is considered to be the modern father of toxicology, having given the subject its first formal treatment in 1813 in his Traité des poisons, also called Toxicologie générale.^[2]

Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493–1541) (also referred to as Paracelsus, from his belief that his studies were above or beyond the work of Celsus - a Roman physician from the first century) is also considered "the father" of toxicology.^[3] He is credited with the classic toxicology maxim, "Alle Dinge sind Gift und nichts ist ohne Gift; allein die Dosis macht, dass ein Ding kein Gift ist." which translates as, "All things are poison and nothing is without poison; only the dose makes a thing not a poison." This is often condensed to: "The dose makes the poison".

An even earlier writer on toxicology was Ibn Wahshiya (Arabic: أبو بكر أحمد بن وحشية Abu Bakr Ahmed ibn Wahshiyah ), who wrote the Book on Poisons in the 9th or 10th century.^[4]

Relationship between dose and toxicity

The relationship between dose and its effects on the exposed organism is of high significance in toxicology. The chief criterion regarding the toxicity of a chemical is the dose, i.e. the amount of exposure to the substance. All substances are toxic under the right conditions. The term LD₅₀ refers to the dose of a toxic substance that kills 50 percent of a test population (typically rats or other surrogates when the test concerns human toxicity). LD₅₀ estimations in animals are no longer required for regulatory submissions as a part of pre-clinical development package.^{[citation needed]}

The conventional relationship (more exposure equals higher risk) has been challenged in the study of endocrine disruptors.

Toxicity of metabolites

Many substances regarded as poisons are toxic only indirectly. An example is "wood alcohol," or methanol, which is chemically converted to formaldehyde and formic acid in the liver. It is the formaldehyde and formic acid that cause the toxic effects of methanol exposure. As for drugs, many small molecules are made toxic in the liver, a good example being acetaminophen (paracetamol), especially in the presence of chronic alcohol use. The genetic variability of certain liver enzymes makes the toxicity of many compounds differ between one individual and the next. Because demands placed on one liver enzyme can induce activity in another, many molecules become toxic only in combination with others. A family of activities that engages many toxicologists includes identifying which liver enzymes convert a molecule into a poison, what are the toxic products of the conversion and under what conditions and in which individuals this conversion takes place.

Subdisciplines of toxicology

There are various specialized subdisciplines within the field of toxicology that concern diverse chemical and biological aspects of this area. For example, toxicogenomics involves applying molecular profiling approaches to the study of toxicology.^[5] Other areas include Aquatic toxicology, Chemical toxicology, Ecotoxicology, Environmental toxicology, Forensic toxicology, and Medical toxicology.

Chemical toxicology

Chemical toxicology is a scientific discipline involving the study of structure and mechanism related to the toxic effects of chemical agents, and encompasses technology advances in research related to chemical aspects of toxicology. Research in this area is strongly multidisciplinary, spanning computational chemistry and synthetic chemistry, proteomics and metabolomics, drug discovery, drug metabolism and mechanisms of action, bioinformatics, bioanalytical chemistry, chemical biology, and molecular epidemiology.

See also

• Aquatic toxicology
• Automatism (toxicology)
• Certain safety factor
• Children's Environmental Exposure Research Study (CHEERS) (in the US)
• Ecotoxicology
• Entomotoxicology
• Environmental toxicology
• Enzyme inhibition
• Forensic toxicology
• In vitro toxicology
• Indicative limit value
• Important publications in toxicology
• Overdose
• Pollution
• Toxic 100 (list of companies)
• Toxicity
• Toxicogenomics

References

1. ^ "What is Toxicology" -Schrager, TF, October 4, 2006
2. ^ U.S. National Library of Medicine, Biography of Mathieu Joseph Bonaventure Orfila (1787–1853)
3. ^ Paracelsus Dose Response in the Handbook of Pesticide Toxicology WILLIAM C KRIEGER / Academic Press Oct01
4. ^ Martin Levey (1966), Medieval Arabic Toxicology: The Book on Poisons of ibn Wahshiya and its Relation to Early Indian and Greek Texts
5. ^ Afshari CA, Hamadeh HK (2004). Toxicogenomics: principles and applications. New York: Wiley-Liss. ISBN 0-471-43417-5. 
   Review: Omenn GS (November 2004). "Toxicogenomics: Principles and Applications". Environ Health Perspect 112 (16): A962. 

Further reading

• Nelson, Lewis H.; Flomenbaum, Neal; Goldfrank, Lewis R.; Hoffman, Robert Louis; Howland, Mary Deems; Neal A. Lewin (2006). Goldfrank's toxicologic emergencies. New York: McGraw-Hill, Medical Pub. Division. ISBN 0-07-147914-7. 
• Richards IS. 2008. Principles and Practice of Toxicology in Public Health. Jones and Bartlett Publisher, Sudbury Massachusetts.

External links

Look up toxicology in Wiktionary, the free dictionary.

• Gilbert SG. A Small Dose of Toxicology – The Health Effects of Common Chemicals. CRC Press, Boca Raton, February 2004, p 266.
• Critical Reviews in Toxicology, A peer-reviewed academic research journal covering all aspects of toxicology, edited by Dr. Roger O. McClellan.
• Agency for Toxic Substances and Disease Registry (ATSDR)
• American College of Medical Toxicology
• European Centre for Ecotoxicology and Toxicology of Chemicals
• Department of Health and Human Services National Toxicology Program (NTP)
• American Association of Poison Control Centers (AAPCC)
• Info. Tox. International Inc.

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Dansk (Danish)
n. - toksikologi, læren om giftstoffer

Nederlands (Dutch)
toxicologie (vergiftenleer)

Français (French)
n. - toxicologie

Deutsch (German)
n. - Toxikologie, Giftkunde

Ελληνική (Greek)
n. - (ιατρ.) τοξικολογία

Italiano (Italian)
tossicologia

Português (Portuguese)
n. - toxicologia (f)

Русский (Russian)
токсикология, учение о ядах и отравлениях

Español (Spanish)
n. - toxicología

Svenska (Swedish)
n. - toxikologi

中文（简体）(Chinese (Simplified))
毒物学, 毒理学

中文（繁體）(Chinese (Traditional))
n. - 毒物學, 毒理學

한국어 (Korean)
n. - 독물학

日本語 (Japanese)
n. - 中毒学, 毒物学

العربيه (Arabic)
‏(الاسم) علم ألسموم‏

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n. - ‮תורת הרעלים, טוקסיקולוגיה‬

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