Toxin

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A toxin is a poisonous substance produced within living cells or organisms; [1] [2] synthetic toxicants created by artificial processes are thus excluded. The term was first used by organic chemist Ludwig Brieger (1849–1919), [3] derived from the word toxic. [4]

Poison substance that causes disturbances to organisms

In biology, poisons are substances that cause disturbances in organisms, usually by chemical reaction or other activity on the molecular scale, when an organism absorbs a sufficient quantity.

A biocide is defined in the European legislation as a chemical substance or microorganism intended to destroy, deter, render harmless, or exert a controlling effect on any harmful organism by chemical or biological means. The US Environmental Protection Agency (EPA) uses a slightly different definition for biocides as "a diverse group of poisonous substances including preservatives, insecticides, disinfectants, and pesticides used for the control of organisms that are harmful to human or animal health or that cause damage to natural or manufactured products". When compared, the two definitions roughly imply the same, although the US EPA definition includes plant protection products and some veterinary medicines.

Contents

Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their toxicity, ranging from usually minor (such as a bee sting) to almost immediately deadly (such as botulinum toxin).

Within the fields of molecular biology and pharmacology, a small molecule is a low molecular weight organic compound that may regulate a biological process, with a size on the order of 1 nm. Most drugs are small molecules. Larger structures such as nucleic acids and proteins, and many polysaccharides are not small molecules, although their constituent monomers are often considered small molecules. Small molecules may be used as research tools to probe biological function as well as leads in the development of new therapeutic agents. Some can inhibit a specific function of a protein or disrupt protein–protein interactions.

Peptides are short chains of amino acid monomers linked by peptide (amide) bonds.

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

Terminology

Toxins are often distinguished from other chemical agents by their method of production—the word toxin does not specify method of delivery (compare with venom and the broader meaning of poison—all substances that can also cause disturbances to organisms). It simply means it is a biologically produced poison.

Venom form of toxin secreted by an animal for the purpose of causing harm to another; poisonous substance injected by animals into a victim

Venom is a secretion containing one or more toxins produced by an animal to cause harm to another. Venom has evolved in a wide variety of animals, both predators and prey, and both vertebrates and invertebrates.

According to an International Committee of the Red Cross review of the Biological Weapons Convention, "Toxins are poisonous products of organisms; unlike biological agents, they are inanimate and not capable of reproducing themselves", and "Since the signing of the Constitution, there have been no disputes among the parties regarding the definition of biological agents or toxins". [5]

International Committee of the Red Cross humanitarian institution

The International Committee of the Red Cross (ICRC) is a humanitarian institution based in Geneva, Switzerland, and a three-time Nobel Prize Laureate. State parties (signatories) to the four Geneva Conventions of 1949 and their Additional Protocols of 1977 and 2005 have given the ICRC a mandate to protect victims of international and internal armed conflicts. Such victims include war wounded, prisoners, refugees, civilians, and other non-combatants.

Biological Weapons Convention Treaty banning production of bioweapons

The Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction was the first multilateral disarmament treaty banning the production of an entire category of weapons.

According to Title 18 of the United States Code, "... the term "toxin" means the toxic material or product of plants, animals, microorganisms (including, but not limited to, bacteria, viruses, fungi, rickettsiae or protozoa), or infectious substances, or a recombinant or synthesized molecule, whatever their origin and method of production..." [6]

Title 18 of the United States Code is the main criminal code of the federal government of the United States. The Title deals with federal crimes and criminal procedure. In its coverage, Title 18 is similar to most U.S. state criminal codes, which typically are referred to by such names as Penal Code, Criminal Code, or Crimes Code. Typical of state criminal codes is the California Penal Code. Many U.S. state criminal codes, unlike the federal Title 18, are based on the Model Penal Code promulgated by the American Law Institute.

Toxicity The ability of a chemical to cause damage to life

Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ such as the liver (hepatotoxicity). By extension, the word may be metaphorically used to describe toxic effects on larger and more complex groups, such as the family unit or society at large. Sometimes the word is more or less synonymous with poisoning in everyday usage.

Plant multicellular eukaryote of the kingdom Plantae

Plants are mainly multicellular, predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, plants were treated as one of two kingdoms including all living things that were not animals, and all algae and fungi were treated as plants. However, all current definitions of Plantae exclude the fungi and some algae, as well as the prokaryotes. By one definition, plants form the clade Viridiplantae, a group that includes the flowering plants, conifers and other gymnosperms, ferns and their allies, hornworts, liverworts, mosses and the green algae, but excludes the red and brown algae.

A rather informal terminology of individual toxins relates them to the anatomical location where their effects are most notable:

Hemotoxins, haemotoxins or hematotoxins are toxins that destroy red blood cells, disrupt blood clotting, and/or cause organ degeneration and generalized tissue damage. The term hemotoxin is to some degree a misnomer since toxins that damage the blood also damage other tissues. Injury from a hemotoxic agent is often very painful and can cause permanent damage and in severe cases death. Loss of an affected limb is possible even with prompt treatment.

Hemolysis or haemolysis, also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid. Hemolysis may occur in vivo or in vitro.

Phototoxins are toxins that can cause allergic reactions in particularly susceptible individuals and which can cause dangerous photosensitivity in a much broader range of subjects.

On a broader scale, toxins may be classified as either exotoxins, being excreted by an organism, or endotoxins, that are released mainly when bacteria are lysed.

Biotoxins

The term "biotoxin" is sometimes used to explicitly confirm the biological origin. [7] [8] Biotoxins can be further classified, for example, as fungal biotoxins, microbial toxins, plant biotoxins, or animal biotoxins.

Toxins produced by microorganisms are important virulence determinants responsible for microbial pathogenicity and/or evasion of the host immune response. [9]

Biotoxins vary greatly in purpose and mechanism, and can be highly complex (the venom of the cone snail contains dozens of small proteins, each targeting a specific nerve channel or receptor), or relatively small protein.

Biotoxins in nature have two primary functions:

Some of the more well known types of biotoxins include:

Environmental toxins

The term "environmental toxin" can sometimes explicitly include synthetic contaminants [10] such as industrial pollutants and other artificially made toxic substances. As this contradicts most formal definitions of the term "toxin", it is important to confirm what the researcher means when encountering the term outside of microbiological contexts.

Environmental toxins from food chains that may be dangerous to human health include:

Finding information about toxins

The Toxicology and Environmental Health Information Program (TEHIP) [21] at the United States National Library of Medicine (NLM) maintains a comprehensive toxicology and environmental health web site that includes access to toxins-related resources produced by TEHIP and by other government agencies and organizations. This web site includes links to databases, bibliographies, tutorials, and other scientific and consumer-oriented resources. TEHIP also is responsible for the Toxicology Data Network (TOXNET), [22] an integrated system of toxicology and environmental health databases that are available free of charge on the web.

TOXMAP is a Geographic Information System (GIS) that is part of TOXNET. TOXMAP uses maps of the United States to help users visually explore data from the United States Environmental Protection Agency's (EPA) Toxics Release Inventory and Superfund Basic Research Programs.

Computational resources for prediction of toxic peptides and proteins

One of the bottlenecks in peptide/protein-based therapy is their toxicity. Recently, in silico models for predicting toxicity of peptides and proteins, developed by Gajendra Pal Singh Raghava's group, [23] predict toxicity with reasonably good accuracy. The prediction models are based on machine learning technique and quantitative matrix using various properties of peptides. The prediction tool is freely accessible to public in the form of web server. [24]

Misuse of the term

When used non-technically, the term "toxin" is often applied to any toxic substance, even though the term toxicant would be more appropriate. Toxic substances not directly of biological origin are also termed poisons and many non-technical and lifestyle journalists follow this usage to refer to toxic substances in general.[ clarification needed ]

In the context of quackery and alternative medicine, the term "toxin" is used to refer to any substance alleged to cause ill health. This could range from trace amounts of potentially dangerous pesticides, to supposedly harmful substances produced in the body by intestinal fermentation (auto-intoxication), to food ingredients such as table sugar, monosodium glutamate (MSG), and aspartame. [25]

See also

Related Research Articles

Red tide A common name for a worldwide phenomenon known as an algal bloom

Red tide is a common name for algal blooms, which are large concentrations of aquatic microorganisms, such as protozoans and unicellular algae. The upwelling of nutrients from the sea floor, often following massive storms, provides for the algae and triggers bloom events. Harmful algal blooms can occur worldwide, and natural cycles can vary regionally.

Algal bloom Rapid increase or accumulation in the population of planktonic algae

An algal bloom or algae bloom is a rapid increase or accumulation in the population of algae in freshwater or marine water systems, and is recognized by the discoloration in the water from their pigments. Cyanobacteria were mistaken for algae in the past, so cyanobacterial blooms are sometimes also called algal blooms. Blooms which can injure animals or the ecology are called "harmful algal blooms" (HAB), and can lead to fish die-offs, cities cutting off water to residents, or states having to close fisheries. Also, a bloom can block out the sunlight from other organisms, and deplete oxygen levels in the water. Also, some algae secrete poisons into the water.

Domoic acid chemical compound

Domoic acid (DA) is a kainic acid analog neurotoxin that causes amnesic shellfish poisoning (ASP). It is produced by algae and accumulates in shellfish, sardines, and anchovies. When sea lions, otters, cetaceans, humans, and other predators eat contaminated animals, poisoning may result. Exposure to this compound affects the brain, causing seizures, and possibly death.

Cyanotoxin

Cyanotoxins are toxins produced by bacteria called cyanobacteria. Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they reproduce exponentially to form blooms. Blooming cyanobacteria can produce cyanotoxins in such concentrations that they poison and even kill animals and humans. Cyanotoxins can also accumulate in other animals such as fish and shellfish, and cause poisonings such as shellfish poisoning.

Saxitoxin chemical compound

Saxitoxin (STX) is a potent neurotoxin and the best-known paralytic shellfish toxin (PST). Ingestion of saxitoxin by humans, usually by consumption of shellfish contaminated by toxic algal blooms, is responsible for the illness known as paralytic shellfish poisoning (PSP).

Tomalley

Tomalley, crab fat, or lobster paste is the soft, green substance found in the body cavity of lobsters, that fulfills the functions of both the liver and the pancreas. Tomalley corresponds to the hepatopancreas in other arthropods. It is considered a delicacy, and may be eaten alone but is often added to sauces for flavour and as a thickening agent. The term lobster paste or lobster pâté can also be used to indicate a mixture of tomalley and lobster roe. Lobster bisque, lobster stock, and lobster consommé are made using lobster bodies (heads), often including the lobster liver.

Paralytic shellfish poisoning Syndrome of shellfish poisoning

Paralytic shellfish poisoning (PSP) is one of the four recognized syndromes of shellfish poisoning, which share some common features and are primarily associated with bivalve mollusks. These shellfish are filter feeders and accumulate neurotoxins, chiefly saxitoxin, produced by microscopic algae, such as dinoflagellates, diatoms, and cyanobacteria. Dinoflagellates of the genus Alexandrium are the most numerous and widespread saxitoxin producers and are responsible for PSP blooms in subarctic, temperate, and tropical locations. The majority of toxic blooms have been caused by the morphospecies Alexandrium catenella, Alexandrium tamarense, and Alexandrium fundyense, which together comprise the A. tamarense species complex. In Asia, PSP is mostly associated with the occurrence of the species Pyrodinium bahamense.

Shellfish poisoning includes four (4) syndromes that share some common features and are primarily associated with bivalve molluscs These shellfish are filter feeders and, therefore, accumulate toxins produced by microscopic algae, such as cyanobacteria, diatoms and dinoflagellates.

Amnesic shellfish poisoning (ASP) is an illness caused by consumption of the marine biotoxin called domoic acid. In mammals, including humans, domoic acid acts as a neurotoxin, causing permanent short-term memory loss, brain damage, and death in severe cases.

Brevetoxin

Brevetoxin (PbTx), or brevetoxins, are a suite of cyclic polyether compounds produced naturally by a species of dinoflagellate known as Karenia brevis. Brevetoxins are neurotoxins that bind to voltage-gated sodium channels in nerve cells, leading to disruption of normal neurological processes and causing the illness clinically described as neurotoxic shellfish poisoning (NSP).

Diarrhetic shellfish poisoning (DSP) is one of the four recognized symptom types of shellfish poisoning, the others being paralytic shellfish poisoning, neurotoxic shellfish poisoning and amnesic shellfish poisoning.

Neurotoxic shellfish poisoning is caused by the consumption of shellfish contaminated by breve-toxins or brevetoxin analogs.

The Hazardous Substances Data Bank (HSDB) is a toxicology database on the U.S. National Library of Medicine's (NLM) Toxicology Data Network (TOXNET). It focuses on the toxicology of potentially hazardous chemicals, and includes information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, and related areas. All data are referenced and derived from a core set of books, government documents, technical reports, and selected primary journal literature. All entries are peer-reviewed by a Scientific Review Panel (SRP), members of which represent a spectrum of professions and interests. Current Chairs of the SRP are Dr. Marcel J. Cassavant, MD, Toxicology Group, and Dr. Roland Everett Langford, PhD, Environmental Fate Group.

Yessotoxin chemical compound

Yessotoxins are a group of lipophilic, sulfur bearing polyether toxins that are related to ciguatoxins. They are produced by a variety of dinoflagellates, most notably Lingulodinium polyedrum and Gonyaulax spinifera.

Neosaxitoxin chemical compound

Neosaxitoxin (NSTX) is included, as other saxitoxin-analogs, in a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). The parent compound of PSTs, saxitoxin (STX), is a tricyclic perhydropurine alkaloid, which can be substituted at various positions, leading to more than 30 naturally occurring STX analogues. All of them are related imidazoline guanidinium derivatives.

Dinotoxins are a group of toxins which are produced by flagellate, aquatic, unicellular protists called dinoflagellates. Dinotoxin was coined by Hardy and Wallace in 2012 as a general term for the variety of toxins produced by dinoflagellates. Dinoflagellates are an enormous group of marine life, with much diversity. With great diversity comes many different toxins, however, there are a few toxins that multiple species have in common.

Canadian Reference Materials (CRM) are certified reference materials of high-quality and reliability produced by the National Metrology Institute of Canada – the National Research Council Canada. The NRC Certified Reference Materials program is operated by the Measurement Science and Standards portfolio and provides CRMs for environmental, biotoxin, food, nutritional supplement, and stable isotope analysis. The program was established in 1976 to produce CRMs for inorganic and organic marine environmental analysis and remains internationally recognized producer of CRMs.

Decarbamoylsaxitoxin

Decarbamoylsaxitoxin, abbreviated as dcSTX, is a neurotoxin which is naturally produced in dinoflagellate. DcSTX is one of the many analogues of saxitoxin (STX).

References

  1. " toxin " at Dorland's Medical Dictionary
  2. "toxin – Definition from the Merriam-Webster Online Dictionary" . Retrieved 13 December 2008.
  3. Brade, Helmut (1999). Endotoxin in Health and Disease. CRC Press. ISBN   978-0824719449 via Google Books.
  4. Harper, Douglas. "toxin". Online Etymology Dictionary .
  5. "The Biological Weapons Convention – An overview" . Retrieved 13 December 2008.
  6. "U.S. Code". Archived from the original on 21 July 2011. Retrieved 13 December 2008.
  7. "biotoxin – Definition from the Merriam-Webster Online Dictionary" . Retrieved 13 December 2008.
  8. " biotoxin " at Dorland's Medical Dictionary
  9. Proft T, ed. (2009). Microbial Toxins: Current Research and Future Trends. Caister Academic Press. ISBN   978-1-904455-44-8.
  10. Grigg J (March 2004). "Environmental toxins; their impact on children's health". Arch. Dis. Child. 89 (3): 244–50. doi:10.1136/adc.2002.022202. PMC   1719840 . PMID   14977703.
  11. Vale C, Alfonso A, Vieytes MR, Romarís XM, Arévalo F, Botana AM, Botana LM (March 2008). "In vitro and in vivo evaluation of paralytic shellfish poisoning toxin potency and the influence of the pH of extraction". Anal. Chem. 80 (5): 1770–76. doi:10.1021/ac7022266. PMID   18232710.
  12. Oikawa H, Fujita T, Saito K, Satomi M, Yano Y (2008). "Difference in the level of paralytic shellfish poisoning toxin accumulation between the crabs Telmessus acutidens and Charybdis japonica collected in Onahama, Fukushima Prefecture". Fisheries Science. 73 (2): 395–403. doi:10.1111/j.1444-2906.2007.01347.x.
  13. Abouabdellah R, Taleb H, Bennouna A, Erler K, Chafik A, Moukrim A (April 2008). "Paralytic shellfish poisoning toxin profile of mussels Perna perna from southern Atlantic coasts of Morocco". Toxicon. 51 (5): 780–86. doi:10.1016/j.toxicon.2007.12.004. PMID   18237757.
  14. Wang L, Liang XF, Zhang WB, Mai KS, Huang Y, Shen D (November 2009). "Amnesic shellfish poisoning toxin stimulates the transcription of CYP1A possibly through AHR and ARNT in the liver of red sea bream Pagrus major". Mar. Pollut. Bull. 58 (11): 1643–48. doi:10.1016/j.marpolbul.2009.07.004. PMID   19665739.
  15. Wang L, Vaquero E, Leão JM, Gogo-Martínez A, Rodríguez Vázquez JA (2001). "Optimization of conditions for the liquid chromatographic-electrospray lonization-mass spectrometric analysis of amnesic shellfish poisoning toxins". Chromatographia . 53 (1): S231–35. doi:10.1007/BF02490333.
  16. Mouratidou T, Kaniou-Grigoriadou I, Samara C, Kouimtzis T (August 2006). "Detection of the marine toxin okadaic acid in mussels during a diarrhetic shellfish poisoning (DSP) episode in Thermaikos Gulf, Greece, using biological, chemical and immunological methods". Sci. Total Environ. 366 (2–3): 894–904. Bibcode:2006ScTEn.366..894M. doi:10.1016/j.scitotenv.2005.03.002. PMID   16815531.
  17. Doucet E, Ross NN, Quilliam MA (September 2007). "Enzymatic hydrolysis of esterified diarrhetic shellfish poisoning toxins and pectenotoxins". Anal Bioanal Chem. 389 (1): 335–42. doi:10.1007/s00216-007-1489-3. PMID   17661021.
  18. Poli MA, Musser SM, Dickey RW, Eilers PP, Hall S (July 2000). "Neurotoxic shellfish poisoning and brevetoxin metabolites: a case study from Florida". Toxicon. 38 (7): 981–93. doi:10.1016/S0041-0101(99)00191-9. PMID   10728835.
  19. Morohashi A, Satake M, Murata K, Naoki H, Kaspar HF, Yasumoto T (1995). "Brevetoxin B3, a new brevetoxin nalog isolated from the greenshell mussel perna canaliculus involved in neurotoxic shellfish poisoning in new zealand". Tetrahedron Letters . 36 (49): 8995–98. doi:10.1016/0040-4039(95)01969-O.
  20. Morohashi A, Satake M, Naoki H, Kaspar HF, Oshima Y, Yasumoto T (1999). "Brevetoxin B4 isolated from greenshell mussels Perna canaliculus, the major toxin involved in neurotoxic shellfish poisoning in New Zealand". Nat. Toxins. 7 (2): 45–48. doi:10.1002/(SICI)1522-7189(199903/04)7:2<45::AID-NT34>3.0.CO;2-H. PMID   10495465.
  21. "Environmental Health and Toxicology Information ? National Library of Medicine". sis.nlm.nih.gov.
  22. "TOXNET". toxnet.nlm.nih.gov.
  23. Gupta S, Kapoor P, Chaudhary K, Gautam A, Kumar R, Raghava GP (2013). "In silico approach for predicting toxicity of peptides and proteins". PLoS ONE. 8 (9): e73957. Bibcode:2013PLoSO...873957G. doi:10.1371/journal.pone.0073957. PMC   3772798 . PMID   24058508.
  24. "ToxinPred". crdd.osdd.net.
  25. ""Detoxification" Schemes and Scams". Quackwatch.