Toxin

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]

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).

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.

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]

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]

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

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:

  • Predation, such as in the spider, snake, scorpion, jellyfish, and wasp
  • Defense as in the bee, ant, termite, honey bee, wasp, and poison dart frog

Some of the more well known types of biotoxins include:

  • Cyanotoxins, produced by cyanobacteria
  • Dinotoxins, produced by dinoflagellates
  • Necrotoxins cause necrosis (i.e., death) in the cells they encounter and destroy all types of tissue. Necrotoxins spread through the bloodstream. In humans, skin and muscle tissues are most sensitive to necrotoxins. Organisms that possess necrotoxins include:
    • The brown recluse or "fiddle back" spider
    • Most rattlesnakes and vipers produce phospholipase and various trypsin-like serine proteases
    • Puff adder
    • Necrotizing fasciitis (caused by the "flesh eating" bacterium Streptococcus pyogenes) – produces a pore forming toxin
  • Neurotoxins primarily affect the nervous systems of animals. The group neurotoxins generally consists of ion channel toxins that disrupt ion channel conductance. Organisms that possess neurotoxins include:
    • The black widow spider.
    • Most scorpions
    • The box jellyfish
    • Elapid snakes
    • The cone snail
    • The Blue-ringed octopus
    • Venomous fish
    • Frogs
    • Palythoa coral
    • Various different types of algae, cyanobacteria and dinoflagellates
  • Myotoxins are small, basic peptides found in snake and lizard venoms, They cause muscle tissue damage by a non enzymatic receptor based mechanism. Organisms that possess myotoxins include:
    • rattlesnakes
    • eastern bearded dragon
  • Cytotoxins are toxic at the level of individual cells, either in a non-specific fashion or only in certain types of living cells:
    • Ricin, from castor beans
    • Apitoxin, from honey bees
    • T-2 mycotoxin, from certain toxic mushrooms
    • Cardiotoxin III, from Chinese cobra

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

In general, when scientists determine the amount of a substance that may be hazardous for humans, animals and/or the environment they determine the amount of the substance likely to trigger effects and if possible establish a safe level. In Europe, the European Food Safety Authority produced risk assessments for more than 4,000 substances in over 1,600 scientific opinions and they provide open access summaries of human health, animal health and ecological hazard assessments in their: OpenFoodTox[21] database. [22][23] The OpenFoodTox database can be used to screen potential new foods for toxicity.[24]

The Toxicology and Environmental Health Information Program (TEHIP)[25] 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.[26] 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),[27] 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.[28] 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,[29] 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.[30]

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.

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.[31]

See also

References

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  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
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  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". Analytical Chemistry. 80 (5): 1770–6. 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): 780–6. 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". Marine Pollution Bulletin. 58 (11): 1643–8. doi:10.1016/j.marpolbul.2009.07.004. PMID 19665739.
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  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". Natural Toxins. 7 (2): 45–8. doi:10.1002/(SICI)1522-7189(199903/04)7:2<45::AID-NT34>3.0.CO;2-H. PMID 10495465.
  21. "Chemical hazards data - OpenFoodTox". European Food Safety Authority. Retrieved 27 October 2019.
  22. Dorne JL, Richardson J, Kass G, Georgiadis N, Monguidi M, Pasinato L, Cappe S, Verhagen H, Robinson T (January 2017). "OpenFoodTox: EFSA's open source toxicological database on chemical hazards in food and feed". EFSA Journal. 15 (1): e15011. doi:10.2903/j.efsa.2017.e15011.
  23. Reilly L, Serafimova R, Partosch F, Gundert-Remy U, Cortiñas Abrahantes J, Dorne JM, Kass GE (October 2019). "Testing the thresholds of toxicological concern values using a new database for food-related substances". Toxicology Letters. 314: 117–123. doi:10.1016/j.toxlet.2019.07.019. PMID 31325634.
  24. Pearce JM, Khaksari M, Denkenberger D (April 2019). "Preliminary Automated Determination of Edibility of Alternative Foods: Non-Targeted Screening for Toxins in Red Maple Leaf Concentrate". Plants. 8 (5): 110. doi:10.3390/plants8050110. PMC 6571818. PMID 31027336.
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  29. 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.
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  31. ""Detoxification" Schemes and Scams". Quackwatch.
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