What is the most lethal toxin?
Botulinum toxin
Botulinum toxin (BTX) is a neurotoxic protein produced by the bacterium "Clostridium botulinum" and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis. Infection with the bacterium causes the disease botulism. The toxin is also used commercially in medicine, cosmetics and research.
Botulinum is the most acutely lethal toxin known, with an estimated human median lethal dose (LD) of 1.3–2.1 ng/kg intravenously or intramuscularly and 10–13 ng/kg when inhaled.
Golden poison frog
Thus, the high toxicity of "P. terribilis" appears to be due to the consumption of small insects or other arthropods, and one of these may truly be the most poisonous creature on Earth. Scientists have suggested the crucial insect may be a small beetle from the family Melyridae. At least one species of these beetles produces the same toxin found in "P. terribilis". Their relatives in Colombian rainforests could be the source of the batrachotoxins found in the highly toxic "Phyllobates" frogs of that region.
Necrotizing fasciitis
"Clostridium sordellii" can also produce two major toxins: all known virulent strains produce the essential virulence factor lethal toxin (TcsL), and a number also produce haemorrhagic toxin (TcsH). TcsL and TcsH are both members of the large clostridial cytotoxin (LCC) family. The key "Clostridium septicum" virulence factor is a pore-forming toxin called alpha-toxin, though it is unrelated to the "Clostridium perfringens" alpha-toxin. Myonecrotic infections caused by these clostridial species commonly occur in injecting heroin users. Those with clostridial infections typically have severe pain at the wound site, where the wound typically drains foul-smelling blood mixed with serum (serosanguinous discharge). Shock can progress rapidly after initial injury or infection, and once the state of shock is established, the chance of dying exceeds 50%. Another bacterium associated with similar rapid disease progression is group A streptococcal infection (mostly "Streptococcus pyogenes"). Meanwhile, other bacterial infections require two or more days to become symptomatic.
Pumiliotoxin
Pumiliotoxins (PTXs), are one of several toxins found in the skin of poison dart frogs. Closely related, though more toxic, are allopumiliotoxins, (aPTXs). Other toxins found in the skin of poison frogs include decahydroquinolines (DHQs), izidines, coccinellines, and spiropyrrolizidines. Pumiliotoxins are very poisonous in high concentrations. Pumiliotoxins are much weaker than batrachotoxins, ranging between 100 and 1000 times less poisonous. There are three different types of this toxin: A, B and C, of which toxins A and B are more toxic than C. Pumiliotoxins interfere with muscle contraction by affecting calcium channels, causing partial paralysis, difficulty moving, hyperactivity, or death.
Aquatic toxicology
Toxicity can be broken down into two broad categories of direct and indirect toxicity. Direct toxicity results from a toxicant acting at the site of action in or on the organism. Indirect toxicity occurs with a change in the physical, chemical, or biological environment.
Lethality is most common effect used in toxicology and used as an endpoint for acute toxicity tests. While conducting chronic toxicity tests sublethal effects are endpoints that are looked at. These endpoints include behavioral, physiological, biochemical, histological changes.
There are a number of effects that occur when an organism is simultaneously exposed to two or more toxicants. These effects include additive effects, synergistic effects, potentiation effects, and antagonistic effects. An additive effect occurs when combined effect is equal to a combination or sum of the individual effects. A synergistic effect occurs when the combination of effects is much greater than the two individual effects added together. Potentiation is an effect that occurs when an individual chemical has no effect is added to a toxicant and the combination has a greater effect than just the toxicant alone. Finally, an antagonistic effect occurs when a combination of chemicals has less of an effect than the sum of their individual effects.
All terms were derived from Rand.
Menthofuran
Menthofuran is an organic compound found in a variety of essential oils including that of Pennyroyal. It is highly toxic and believed to be the primary toxin in Pennyroyal responsible for its potentially fatal effects. After ingestion of menthofuran, it is metabolically activated to chemically reactive intermediates that are hepatotoxic.
Neurotoxin
Mercury is capable of inducing CNS damage by migrating into the brain by crossing the BBB. Mercury exists in a number of different compounds, though methylmercury (MeHg), dimethylmercury and diethylmercury are the only significantly neurotoxic forms. Diethylmercury and dimethylmercury are considered some of the most potent neurotoxins ever discovered. MeHg is usually acquired through consumption of seafood, as it tends to concentrate in organisms high on the food chain. It is known that the mercuric ion inhibits amino acid (AA) and glutamate (Glu) transport, potentially leading to excitotoxic effects.
Sodium cyanide
Sodium cyanide, like other soluble cyanide salts, is among the most rapidly acting of all known poisons. NaCN is a potent inhibitor of respiration, acting on mitochondrial cytochrome oxidase and hence blocking electron transport. This results in decreased oxidative metabolism and oxygen utilization. Lactic acidosis then occurs as a consequence of anaerobic metabolism. An oral dosage as small as 200–300 mg can be fatal.
Cerastocytin
Snake venom contains toxins capable of causing death to the reptile’s prey in many various ways. Most of the toxins fall into one of the two categories: elapid (mainly neurotoxic) or viperid (mainly hemotoxic) toxins depending on the immediate cause of death. Elapid snakes cause prey to die from asphyxiation because the dominating neurotoxins inhibit cholinesterase activity, thereby leading to paralysis of all muscles, including the diaphragm. The immediate cause of death after bites of viperid snakes is a sudden drop in blood pressure or stroke as the hemotoxins, mostly prevalent in this type of venom, induce either extensive coagulation or bleeding. While snakes are categorized in this manner, venom of either type may include a number of toxic enzymes involved in neurotoxicity, hemotoxicity, nutrient digestion and other functions necessary to make the prey available for consumption.
Botulism
"Clostridium botulinum" is an anaerobic, Gram positive, spore-forming rod. Botulinum toxin is one of the most powerful known toxins: about one microgram is lethal to humans when inhaled. It acts by blocking nerve function (neuromuscular blockade) through inhibition of the excitatory neurotransmitter acetylcholine's release from the presynaptic membrane of neuromuscular junctions in the somatic nervous system. This causes paralysis. Advanced botulism can cause respiratory failure by paralysing the muscles of the chest; this can progress to respiratory arrest. Furthermore, acetylcholine release from the presynaptic membranes of muscarinic nerve synapses is blocked. This can lead to a variety of autonomic signs and symptoms described above.
Tetanospasmin
Tetanus toxin is an extremely potent neurotoxin produced by the vegetative cell of "Clostridium tetani" in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is also called spasmogenic toxin, or TeNT. The LD of this toxin has been measured to be approximately 2.5-3 ng/kg, making it second only to botulinum toxin (LD 2 ng/kg) as the deadliest toxin in the world. However, these tests are conducted solely on mice, which may react to the toxin differently from humans and other animals.
Cephalopod attack
All octopuses have venom, but few are fatally dangerous. The greater blue-ringed octopus, however, is considered to be one of the most venomous animals known; the venom of one is enough to kill ten grown men. It uses the neurotoxin tetrodotoxin, which quickly causes respiratory arrest. Estimates of the number of recorded fatalities caused by blue-ringed octopuses vary, ranging from seven to sixteen deaths; most scholars agree that there are at least eleven.
Inland taipan
The inland taipan is the most venomous snake in the world. Based on the median lethal dose value in mice, its venom, drop for drop, is by far the most toxic of any snake – much more so than even sea snakes – and it has the most toxic venom of any reptile when tested on human heart cell culture. Unlike most snakes, the inland taipan is a specialist mammal hunter so its venom is specially adapted to kill warm-blooded species. It is estimated that one bite possesses enough lethality to kill at least 100 fully grown men, and, depending on the nature of the bite, it has the potential to kill someone in as little as 30 to 45 minutes if left untreated. It is an extremely fast and agile snake that can strike instantly with extreme accuracy, often striking multiple times in the same attack, and it envenoms in almost every case.
Harry Stone Mosher
While at Stanford, Mosher taught organic chemistry and conducted research in natural products chemistry and stereochemistry. He and his graduate student Melanchton Brown identified a deadly toxin produced by the California newt living in Stanford's Lake Lagunita, calling it tarichatoxin. They soon discovered that it was the same toxin produced by the puffer fish, used in a rare type of sushi that if prepared incorrectly could paralyze and kill human diners. Mosher determined the structure of the toxin, which is known as tetrodotoxin. Mosher worked on many other natural products including both plant pigments and toxic substances.
Polyethoxylated tallow amine
A review of the literature provided to the EPA in 1997 found that POEA was generally more potent in causing toxicity to aquatic organisms than glyphosate, and that POEA becomes more potent in more alkaline environments. (Potency is measured by the median lethal dose (LD50); a low LD50 means that just a little of the substance is lethal; a high LD50 means that it takes a high dose to kill.) Glyphosate has an LD50 ranging from 4.2 times that of POEA for midge larvae at pH 6.5, to 369 times that of POEA for rainbow trout at pH 9.5 (for comparison, at pH 6.5 the LC50 of glyphosate was 70 times that of POEA for rainbow trout). The pH value of most freshwater streams and lakes is between 6.0 and 9.0; fish species are harmed by water having a pH value outside of this range.
Poisonous amphibian
Except certain salamandrid salamanders that can extrude sharp venom-tipped ribs, amphibians are not known to actively inject venom. Most toxic amphibians are instead known to be poisonous to touch or eat. Amphibians usually sequester toxins from animals and plants on which they feed, commonly from poisonous insects or poisonous plants. One example of this is the well-known poison dart frog. They get a deadly chemical called lipophilic alkaloid from consuming a poisonous food in the rainforest. They are immune to the poison and they secrete it through their skin as a defense mechanism against predators. This poison is so efficient, the native people of the South American Amazon rainforest use the frogs' toxins on their weapons to kill their prey, giving the frogs their nickname the "poison dart frog". Some people use the bufotoxins of some species of toxic toads as a drug to get high, but this can become very dangerous. Usually due to the toads' size and toxicity, the poisons would not be deadly to a fully grown, healthy adult. But if too much of the toxin is absorbed, or if the person is young or ill, then the poisons can become a serious threat. It also depends on species: some amphibians do have toxins strong enough to kill even a healthy mature person within just a few minutes, while other species may not have toxins potent enough to have any effect. Licking toads is not biologically practical. For these tryptamines to be orally activated, the human monoamine oxidase system must be inhibited. Therefore, licking a poisonous amphibian will not guarantee a sufficient dose.
Toxic equivalency factor
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the reference chemical to which the toxicity of other dioxins and DLCs are compared. TCDD is the most toxic DLC known. Other dioxins and DLCs are assigned a scaling factor, or TEF, in comparison to TCDD. TCDD has a TEF of 1.0. Sometimes PCB126 is also used as a reference chemical, with a TEF of 0.1.
Mamushi
The venom of this species varies very little among Japan, China, and Korea in terms of both its potency and its effects. According to Yoshimitsu (2005), this species and the Okinawan habu, another pitviper, are the most venomous snakes in Japan. The venom's lethality as measured by LD in mice following intraperitoneal injection is in the range 0.3 mg/kg to 1.22 mg/kg. The venom mostly contains haemolytic toxins, but it also has two neurotoxins—an alpha-toxin that is a post-synaptic inhibitor and a beta-toxin that is a pre-synaptic inhibitor. Because the beta-toxin acts pre-synaptically, its effects cannot be blocked or treated by anticholinesterases. The venom contains an anticoagulant, mamushi L-amino-acid oxidase (M-LAO). It also contains the peptide ablomin which is highly similar in amino acid sequence to that of the venom, helothermine, of the beaded lizard ("Heloderma horridum").
Snake venom
These toxins attack cholinergic neurons (those that use ACh as a transmitter) by destroying acetylcholinesterase (AChE). ACh therefore cannot be broken down and stays in the receptor. This causes tetany (involuntary muscle contraction), which can lead to death. The toxins have been called fasciculins since after injection into mice, they cause severe, generalized and long-lasting (5-7 h) fasciculations (rapid muscle contractions).
Metal toxicity
Toxic metals sometimes imitate the action of an essential element in the body, interfering with the metabolic process resulting in illness. Many metals, particularly heavy metals are toxic, but some heavy metals are essential, and some, such as bismuth, have a low toxicity. Most often the definition of toxic metals includes at least cadmium, manganese, lead, mercury and the radioactive metals. Metalloids (arsenic, polonium) may be included in the definition. Radioactive metals have both radiological toxicity and chemical toxicity. Metals in an oxidation state abnormal to the body may also become toxic: chromium(III) is an essential trace element, but chromium(VI) is a carcinogen.
Clostridium difficile toxin B
The involvement of toxin A and—most importantly—toxin B is the key element that determines the disease caused by "C. difficile". Clinical laboratories have identified these toxins in patients' stool based on antibody and cytotoxicity assays. These bacterial toxins have been shown to be associated with "Clostridium sordellii" hemorrhagic toxin (TcsH), lethal toxin (TcsL), and "Clostridium novyi" alpha toxin (Tcn α), thus, making this cohort to be the large family of toxin clostridial. Because of similarities of these toxins with others, researchers have classified them as the family of large clostridial toxins (LCTs).
Leiurus
The venom of "L. quinquestriatus" is among the most potent scorpion toxins. It severely affects the cardiac and pulmonary systems. Human fatalities, often children, have been confirmed by clinical reports. The median lethal dose of venom (LD) for this species was measured at 0.16 - 0.50 mg/kg.
The toxicity of the other species is also potentially high to life-threatening, but reliable data are currently not available.
VX (nerve agent)
VX is a "particularly toxic nerve agent". The potentially fatal dose is only slightly higher than the dose having any effect at all, and the effects of a fatal dose are so rapid that there is little time for treatment. The median lethal dose (LD)—the exposure required to kill half of a tested population—as estimated for 70 kg human males via exposure to the skin is reported to be , and the lethal concentration time (LCt), measuring the concentration of the vapor per length of time exposed, is estimated for VX to be 30–50 mg·min/m.
Pore-forming toxin
ADP-ribosylation is a common enzymatic method used by different bacterial toxins from various species. Toxins such as "C. perfringens" iota toxin and "C. botulinum" C2 toxin, attach a ribosyl-ADP moiety to surface arginine residue 177 of G-actin. This prevents G-actin assembling to form F-actin, and, thus, the cytoskeleton breaks down, resulting in cell death. Insecticidal members of the ADP-ribosyltransferase family of toxins include the Mtx1 toxin of "Lysinibacillus sphaericus" and the Vip1/Vip2 toxin of "Bacillus thuringiensis" and some members of the toxin complex (Tc) toxins from gram negative bacteria such as "Photorhabdus" and "Xenorhabdus" species. The beta sheet-rich regions of the Mtx1 protein are lectin-like sequences that may be involved in glycolipid interactions.
Aipysurus duboisii
The acute toxicity of snake venom is conventionally tested on laboratory animals and is evaluated in terms of the median lethal dose (LD), that is, the dose required to kill half the members of a tested population divided by the weight of the tested animal. The LD depends on the animal. Rabbits are about twice as sensitive to sea snake venom as mice, and fish and frogs are even more susceptible. The LD for subcutaneous injection of "A. duboisii" venom into mice is 0.044 mg/kg of body weight. This makes "A. duboisii" the most venomous sea snake tested, and one of the top three most venomous snakes in the world, together with the inland taipan ("Oxyuranus microlepidotus", LD=0.025 mg/kg) and the eastern brown snake ("Pseudonaja textilis", LD=0.0365 mg/kg).
List of dangerous snakes
The most medically important species of snake bites in Central Asia is the Caspian cobra ("Naja oxiana"). It is the most venomous species of cobra in the world, slightly ahead of the Philippines cobra based on a toxinological study from 1992 found in the Indian Journal of Experimental Biology, in which this species produced the highest potency venom among cobras. The venom of this species has the most potent composition of toxins found among any cobra species known. It is made up of primarily highly potent neurotoxins but it also has cytotoxic activity (tissue-death, necrosis) and cardiotoxins. Two forms of "cytotoxin II" (cardiotoxin) were found in the venom of this species. The crude venom of this species produced the lowest known lethal dose (LCLo) of 0.005 mg/kg, the lowest among all cobra species, derived from an individual case of poisoning by intracerebroventricular injection. A 1992 extensive toxinology study gave a value of 0.18 mg/kg (range of 0.1 mg/kg - 0.26 mg/kg) by subcutaneous injection. According to Brown (1973), the subcutaneous value is 0.4 mg/kg, while Ernst and Zug "et al." list a value of 0.21 mg/kg SC and 0.037 mg/kg IV. Latifi (1984) listed a subcutaneous value of 0.2 mg/kg. In another study, where venom was collected from a number of specimens in Iran, the IV in lab mice was 0.078 mg/kg. Average venom yield per bite for this species is between 75 and 125 mg (dry weight), but it may yield up to 590 mg (dry weight) in a single bite. The bite of this species may cause severe pain and swelling, along with severe neurotoxicity. Weakness, drowsiness, ataxia, hypotension, and paralysis of throat and limbs may appear in less than one hour after the bite. Without medical treatment, symptoms rapidly worsen and death can occur rapidly after a bite due to respiratory failure. An adult woman bitten by this species in northwestern Pakistan suffered severe neurotoxicity and died while en route to the closest hospital nearly 50 minutes after envenomation. Between 1979 and 1987, 136 confirmed bites were attributed to this species in the former Soviet Union. Of the 136, 121 received antivenom, and only four died. Of the 15 who did not receive antivenom, 11 died. This species is an abundant snake in northeastern Iran and is responsible for a very large number of snakebite mortalities. Antivenom is not as effective for envenomation by this species as it is for other Asiatic cobras within the same region, like the Indian cobra ("Naja naja") and due to the dangerous toxicity of this species' venom, massive amounts of antivenom are often required for patients. As a result, a monovalent antivenom serum is being developed by the Razi Vaccine and Serum Research Institute in Iran. The untreated mortality rate for this species is 70-75%, which is the highest among all cobra species of the genus "Naja".
Neurotoxin
As neurotoxins are compounds which adversely affect the nervous system, a number of mechanisms through which they function are through the inhibition of neuron cellular processes. These inhibited processes can range from membrane depolarization mechanisms to inter-neuron communication. By inhibiting the ability for neurons to perform their expected intracellular functions, or pass a signal to a neighboring cell, neurotoxins can induce systemic nervous system arrest as in the case of botulinum toxin, or even nervous tissue death. The time required for the onset of symptoms upon neurotoxin exposure can vary between different toxins, being on the order of hours for botulinum toxin and years for lead.
Chironex fleckeri
Chironex fleckeri, commonly known as the sea wasp, is a species of extremely venomous box jellyfish found in coastal waters from northern Australia and New Guinea north to the Philippines and Vietnam. It has been described as "the most lethal jellyfish in the world", with at least 63 known deaths in Australia from 1884 to 1996.
Neuromuscular junction
Tetanus toxin, also known as tetanospasmin is a potent neurotoxin produced by "Clostridium tetani" and causes the disease state, tetanus. The LD of this toxin has been measured to be approximately 1 ng/kg, making it second only to Botulinum toxin D as the deadliest toxin in the world. It functions very similarly to botunlinum neurotoxin (BoNT) by attaching and endocytosing into the presynaptic nerve terminal and interfering with SNARE protein complexes. It differs from BoNT in a few ways, most apparently in its end state, wherein tetanospasmin demonstrates a rigid / spastic paralysis as opposed to the flaccid paralysis demonstrated with BoNT.
Botulinum toxin
In 1895 (seventy-five years later), Émile van Ermengem, professor of bacteriology and a student of Robert Koch, correctly described "Clostridium botulinum" as the bacterial source of the toxin. Thirty-four attendees at a funeral were poisoned by eating partially salted ham, an extract of which was found to cause botulism-like paralysis in laboratory animals. Van Ermengem isolated and grew the bacterium, and described its toxin, which was later purified by P Tessmer Snipe and Hermann Sommer.
Crotalus tigris
Although it has a comparatively low venom yield, its toxicity is considered to be the second highest of all rattlesnake venoms (next to the mojave), and the second highest of all snakes in the Western Hemisphere. It has a high neurotoxic fraction that is antigenically related to Mojave toxin (see "Crotalus scutulatus", venom A), and includes another component immunologically identical to crotamine, which is a myotoxin also found in tropical rattlesnakes (see "Crotalus durissus"). A low but significant protease activity is in the venom, although it does not seem to have any hemolytic activity.
Phyllobates aurotaenia
"P. aurotaenia" is one of the most lethal species of the poison dart frogs, which is attributed to their storage and release of batrachotoxin from cutaneous granular glands scattered throughout the frogs’ bodies. This extremely potent toxin is a steroidal alkaloid which, in mammals, acts by irreversibly binding to and permanently opening sodium ion channels within nerve and muscle cells. This prevents repolarization of the cell membrane and halts further signaling, resulting in paralysis and often death as any affected muscle becomes locked in the contracted state. In order to avoid self-intoxication the frogs have developed modified sodium channels to prevent the binding of batrachotoxin.
Although wild frogs are extremely deadly, frogs raised in captivity are generally non-toxic. It has therefore been proposed that the frogs do not synthesize batrachotoxin themselves, but it is instead obtained from their environment. Evidence suggests that the frogs accumulate this toxin through their diet of various beetles (ex: Melyrid beetle), millipedes, and flies as well as the unique composition of leaf litter on the forest floor.
Amanita exitialis
The content and distribution of the main amatoxins (alpha-amanitin, beta-amanitin) and phallotoxins (phallacidin, phallisin, phalloin, phalloidin) in the three tissues (cap, stipe and volva) of "Amanita exitialis" have been determined using high-performance liquid chromatography. The cap had the highest content of total toxins, reaching over 8000 µg/g dry weight (µg of toxin per gram of dried tissue), the toxins content in the stem was over 3700 µg/g dry weight, whereas the volva had the lowest content of total toxins, with about 1150 µg/g dry weight. Amatoxins content (alpha-amanitin and beta-amanitins especially alpha-amanitin) in the cap, stem or volva of "A. exitialis" was higher than that of Phallotoxins (Phallacidin, Phallisin, Phalloidin and Phalloin), but the content of phallotoxins (especially phallacidin) was gradually higher from cap to stem and to volva. A 2011 study reported the presence of additional toxins amaninamide, phallacin, phallisacin and desoxoviridin. A Chinese study concluded that this species had the highest mortality rate of all toxic mushrooms in China. It has been estimated that about of fresh mushrooms contains sufficient toxin to cause the death of a adult. In March 2000, nine people consumed the mushroom in Guangzhou, and only one survived. Since 2000, another 20 people have died in the southern provinces of China from consuming the mushroom.
Veratrum nigrum
All parts of the plant are highly toxic. However, the highest concentrations of toxins tend to be in the rhizome. Toxicity varies widely depending on the method of preparation (extract, water extract, etc.), and the method of application. Just per can cause death due to cardiac arrhythmia. Death has even occurred at a dosage as low as .
Latrunculin
Latrunculin is a toxin that is produced by sponges. The red-coloured Latrunculia Magnifica Keller is an abundant sponge in the gulf of Eilat and the gulf of Suez in the red sea, where it lives at a depth of 6–30 meters. The toxin was discovered around 1970. Researchers observed that the red-coloured sponges, Latrunculia Magnifica Keller, were never damaged or eaten by fishes, while others were. Furthermore, when researchers squeezed the sponges in the sea, they observed that a red fluid came out. Fishes nearby immediately fled the surrounding area when the sponge secreted the fluid. This were the first indications that these sponges produced a toxin. Later they confirmed the hypothesis by squeezing the sponge in an aquarium with fish. The fish shown loss of balance and severe bleedings and died within only 4–6 minutes. Similar effects were observed when the toxin was injected in mice.
Maitotoxin
Maitotoxin (or MTX) is an extremely potent toxin produced by "Gambierdiscus toxicus", a dinoflagellate species. Maitotoxin is so potent that it has been demonstrated that an intraperitoneal injection of 130 ng/kg was lethal in mice. Maitotoxin was named from the ciguateric fish "Ctenochaetus striatus"—called "maito" in Tahiti—from which maitotoxin was isolated for the first time. It was later shown that maitotoxin is actually produced by the dinoflagellate "Gambierdiscus toxicus".
Toxin and Toxin-Target Database
The Toxin and Toxin-Target Database (T3DB), also known as the Toxic Exposome Database, is a freely accessible online database of common substances that are toxic to humans, along with their protein, DNA or organ targets. The database currently houses nearly 3,700 toxic compounds or poisons described by nearly 42,000 synonyms. This list includes various groups of toxins, including common pollutants, pesticides, drugs, food toxins, household and industrial/workplace toxins, cigarette toxins, and uremic toxins. These toxic substances are linked to 2,086 corresponding protein/DNA target records. In total there are 42,433 toxic substance-toxin target associations. Each toxic compound record (ToxCard) in T3DB contains nearly 100 data fields and holds information such as chemical properties and descriptors, mechanisms of action, toxicity or lethal dose values, molecular and cellular interactions, medical (symptom and treatment) information (Fig. 1-3), NMR an MS spectra, and up- and down-regulated genes. This information has been extracted from over 18,000 sources, which include other databases, government documents, books, and scientific literature.
Xenon-135
Xenon-135 (Xe) is an unstable isotope of xenon with a half-life of about 9.2 hours. Xe is a fission product of uranium and it is the most powerful known neutron-absorbing nuclear poison (2 million barns; up to 3 million barns under reactor conditions.), with a significant effect on nuclear reactor operation. The ultimate yield of xenon-135 from fission is 6.3%, though most of this is from fission-produced tellurium-135 and iodine-135.
Beta-Amanitin
"beta"-Amanitin or β-amanitin is a cyclic peptide comprising eight amino acids. It is part of a group of toxins called amatoxins, which can be found in several mushrooms belonging to the genus "Amanita". Some examples are the death cap ("Amanita phalloides") and members of the destroying angel complex, which includes "A. virosa" and "A. bisporigera". Due to the presence of α-amanitin, β-amanitin, γ-amanitin and ε-amanitin these mushrooms are highly lethal to human beings.
The lethal dose of amanitoxins is 0.1 mg/kg of body weight of humans. The average Amanita mushroom contains 3–5 mg of amanitoxins, so one 40–50 g mushroom could kill an average adult. The U.S. Occupational Safety and Health Administration (OSHA) permits a time-weighted average exposure of up to 5 mg/m of β-amanitin dust.
Toxicant
Biocides are oxidized or non-oxidized toxicants. Chlorine is the most commonly manufactured oxidized toxicant. Chlorine is ubiquitously added to drinking water to disinfect it. Non-oxidized toxicants include isothiazolinones and quaternary ammonium compounds.
Trichothecene
The trichothecene mycotoxins are toxic to humans, other mammals, birds, fish, a variety of invertebrates, plants, and eukaryotic cells. The specific toxicity varies depending on the particular toxin and animal species, however the route of administration plays a significantly higher role in determining lethality. The effects of poisoning will depend on the concentration of exposure, length of time and way the person is exposed. A highly concentrated solution or large amount of the gas is more likely to cause severe effects, including death. Upon consumption, the toxin inhibits ribosomal protein, DNA and RNA synthesis, mitochondrial functions cell division while simultaneously activating a cellular stress response named ribotoxic stress response
Alexandrium catenella
The dinoflagellate produces saxitoxin, which is a highly potent neurotoxin. If consumed, this toxin can cause paralytic shellfish poisoning (PSP). By ingesting saxitoxin, humans can suffer from numbness, ataxia, incoherence, and in extreme cases respiratory paralysis and death. The toxin was discovered in 1927 in central California. Shellfish poisoning affected over a hundred humans, and now saxitoxin is recognized as one of the most deadly algal toxins.
Delta-palutoxin
The four δ-Palutoxins show a strong paralytic activity against "Spodoptera litura" larvae but also against some other insects. The LD50 values for δ-Palutoxin-IT1 to IT3 range from 9,5 – 24,7 µg per gram insect. δ-Palutoxin-IT1 is the most active toxin, followed by δ-Palutoxin-IT2, and δ-Palutoxin-IT4 has the lowest activity. δ-Palutoxins are insect selective, no persistent toxic effect was found on mice. The structural basis for the selectivity of these toxins for insects over the mammalian sodium ion channels is still largely unknown.
Cicuta
All members of "Cicuta" except "C. bulbifera" contain high levels of the poisonous principle cicutoxin, an unsaturated aliphatic alcohol that is structurally closely related to the toxin oenanthotoxin found in the plant hemlock water dropwort. Cicutoxin is present at all stages of growth and in all parts of the plant, but is most concentrated in the roots which appear to be the most toxic in the early spring. Its primary toxic effect is to act as a stimulant in the central nervous system. It is a non-competitive gamma-aminobutyric acid (GABA) receptor antagonist. Cicutoxin acts on the GABA receptor causing a block of the chloride channel which results in neuronal depolarization. In the presence of cicutoxin this depolarization continues unabated causing cell overactivity. The hyperactivity in brain cells results in seizures. Cicutoxin is highly poisonous and water hemlock is considered one of North America's most toxic plants. Ingestion of "Cicuta" can be fatal in humans and there are reports in the medical literature of severe poisoning and death as early as 1670. A number of people have also died following ingestion of the plant in the 20th and 21st century.
Venomous snake
Belcher's sea snake ("Hydrophis belcheri"), which many times is mistakenly called the hook-nosed sea snake ("Enhydrina schistosa"), has been erroneously popularized as the most venomous snake in the world, due to the first edition of Ernst and book, "Snakes in Question: The Smithsonian Answer Book", published in 1996.
Prominent venom expert Associate Professor Bryan Grieg Fry has clarified the error: "The hook nosed myth was due to a fundamental error in a book called "Snakes in Question". In there, all the toxicity testing results were lumped in together, regardless of the mode of testing (e.g., subcutaneous vs. intramuscular vs. intravenous vs. intraperitoneal). As the mode can influence the relative number, venoms can only be compared within a mode. Otherwise, it's apples and rocks." Belcher's sea snake's actual LD (recorded only intramuscularly) is 0.24 mg/kg and 0.155 mg/kg. Studies on mice and human cardiac cell culture show that venom of the inland taipan, drop by drop, is the most toxic among all snakes.
Neurotoxin
When it was first discovered, the toxin was called the Very Fast Death Factor (VFDF) because when it was injected into the body cavity of mice it induced tremors, paralysis and death within a few minutes. In 1977, the structure of VFDF was determined as a secondary, bicyclic amine alkaloid, and it was renamed anatoxin-"a". Structurally, it is similar to cocaine. There is continued interest in anatoxin-"a" because of the dangers it presents to recreational and drinking waters, and because it is a particularly useful molecule for investigating acetylcholine receptors in the nervous system. The deadliness of the toxin means that it has a high military potential as a toxin weapon.
List of dangerous snakes
The Tiger rattlesnake ("Crotalus tigris") has a comparatively low venom yield but is considered to have the most toxic of all rattlesnake venoms, and the highest venom toxicity of all snakes in the Western Hemisphere. Although they're reluctant to bite, tiger rattlensakes are known to be cantankerous and aggressive . Because of their tendency to stand their ground and aggressively defend themselves, they pose a serious threat to humans. Tiger rattlesnake venom has a high neurotoxic fraction that is antigenically related to Mojave toxin (see "Crotalus scutulatus", venom A), and includes another component immunologically identical to crotamine, a myotoxin also found in tropical rattlesnakes (see "Crotalus durissus"). The venom has low but significant protease activity, although there does not seem to be any hemolytic activity. Brown (1973) lists an average venom yield of 11 mg (dried venom) and values of 0.07 mg/kg IP, 0.056 mg/kg IV, and 0.21 mg/kg SC. Minton and Weinstein (1984) list an average venom yield of 6.4 mg (based on two specimens). Weinstein and Smith (1990) list a venom yield of 10 mg. Humans are rarely bitten by the tiger rattlesnake, and literature available on bites by this snake is scarce. The several recorded human envenomations by tiger rattlesnakes produced little local pain, swelling, or other reaction following the bite and, despite the toxicity of its venom, no significant systemic symptoms have been recorded. The comparatively low venom yield (6.4–11 mg dried venom) and short to fangs of the tiger rattlesnake possibly prevent severe envenoming in adult humans. However, the clinical picture could be much more serious if the person bitten was a child or an individual with a slight build. The early therapeutic use of antivenom is important if significant envenomation is suspected. Despite the low venom yield, a bite by this rattlesnake should be considered a life-threatening medical emergency. Untreated mortality rate is unknown.
Alpha particle
Due to the short range of absorption and inability to penetrate the outer layers of skin, alpha particles are not, in general, dangerous to life unless the source is ingested or inhaled. Because of this high mass and strong absorption, if alpha-emitting radionuclides do enter the body (upon being inhaled, ingested, or injected, as with the use of Thorotrast for high-quality X-ray images prior to the 1950s), alpha radiation is the most destructive form of ionizing radiation. It is the most strongly ionizing, and with large enough doses can cause any or all of the symptoms of radiation poisoning. It is estimated that chromosome damage from alpha particles is anywhere from 10 to 1000 times greater than that caused by an equivalent amount of gamma or beta radiation, with the average being set at 20 times. A study of European nuclear workers exposed internally to alpha radiation from plutonium and uranium found that when relative biological effectiveness is considered to be 20, the carcinogenic potential (in terms of lung cancer) of alpha radiation appears to be consistent with that reported for doses of external gamma radiation i.e. a given dose of alpha-particles inhaled presents the same risk as a 20-times higher dose of gamma radiation. The powerful alpha emitter polonium-210 (a milligram of Po emits as many alpha particles per second as 4.215 grams of Ra) is suspected of playing a role in lung cancer and bladder cancer related to tobacco smoking. Po was used to kill Russian dissident and ex-FSB officer Alexander V. Litvinenko in 2006.
Botulinum toxin
The effects of botulinum toxin are different from those of nerve agents involved insofar in that botulism symptoms develop relatively slowly (over several days), while nerve agent effects are generally much more rapid and can be instantaneous. Evidence suggests that nerve exposure (simulated by injection of atropine and pralidoxime) will increase mortality by enhancing botulinum toxin's mechanism of toxicity.
Toxic injury
Every toxic injury or expsoure to a toxin has different effects and symptoms. Some toxic effects do not necessarily cause permanent damage and can be reversible. However, some toxins can cause irreversible permanent damage. Depending on the intensity of the poison of the substance it can affect just one particular organ system or they may produce generalized toxicity by affecting a number of systems. A variety of symptoms occur depending on how and where the toxic injuries affect the body. Generally, if the toxins affect the respiratory system the symptoms are coughing, tight chest, difficulty in breathing and nose and throat irritation. Miscarriage or infertility can occur if it occurs in the ovaries or testes.Depression, severe headaches and dizziness are the symptoms for toxins affecting the spinal cord and brain. Visible reactions such as skin rashes, and swelling and eye redness are common. Exposure to asbestos can lead to Mesothelioma which is a cancer that can cause serious damage to the lining of the lungs. The symptoms include shortness of breath, cough, night sweats and fever.
Poison
Biologically speaking, any substance, if given in large enough amounts, is poisonous and can cause death. For instance, several kilograms worth of water would constitute a lethal dose. Many substances used as medications—such as fentanyl—have an only one order of magnitude greater than the ED50. An alternative classification distinguishes between lethal substances that provide a therapeutic value and those that do not.
Ichthyotoxin
Ichthyotoxins are compounds which are either toxic to fish or are toxins produced by fish. The toxins can be found in gar eggs and the eggs of several other species' roe. It can also be found in some species of algae such as prymnesium parvum. They include euglenophycin and prymnesins, made by algae and can cause large-scale fish deaths, and ostracitoxin made by boxfish. Many toxin producing algal species can be found both in marine and fresh water environments when the algae is in bloom. The toxin is protein based and is poisonous to humans, small mammals, and some fish. An ichthyotoxic poisoning (in humans) can cause symptoms ranging in severity dependent on how much toxin was consumed. The symptoms of an ichthyotoxin poisoning can include headache, vomiting, diarrhea, dizziness, drop in blood pressure, and many others.
Anthrax toxin
Anthrax is a disease caused by "Bacillus anthracis", a spore-forming, Gram positive, rod-shaped bacterium (Fig. 1). The lethality of the disease is caused by the bacterium's two principal virulence factors: (i) the polyglutamic acid capsule, which is anti-phagocytic, and (ii) the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: (i) protective antigen (PA), (ii) edema factor (EF), and (iii) lethal factor (LF).
Microbial toxin
Microbial toxins are toxins produced by micro-organisms, including bacteria and fungi. Microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Some bacterial toxins, such as "Botulinum" neurotoxins, are the most potent natural toxins known. However, microbial toxins also have important uses in medical science and research. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.
Palythoa toxica
"P. toxica" contains palytoxin, one of the most poisonous substances known. This zoanthid is not the only member of its genus to contain the toxin; that distinction is shared by "P. tuberculosa". The latter species has a seasonal cycle, varying in toxicity at different times of year, whereas "P. toxica" is equally toxic all year round. Other species of "Palythoa" have also been shown to contain the substance in varying amounts at different times and in different places, and some algae and certain crabs and fish have been found to contain it. It has been suggested that the toxin is actually produced by a dinoflagellate, "Ostreopsis" spp., and incorporated into the zoanthid tissues, possibly through a symbiotic relationship similar to that of zooxanthellae in coral.
Polymorphic toxins
Each family of PTs is defined by a conserved N-terminal region associated with diverse C-terminal (CT) toxic domains, which can be found in several other PT families. The fact that toxic domains are shared between several families of PTs is a hallmark of this category of toxins. A pool of more than 150 distinct toxic domains have been predicted by an in silico study. The most frequent toxic activities found among PTs are RNases, DNases, peptidases and protein-modifying activities.
Galerina sulciceps
"Galerina sulciceps" is deadly poisonous; one author opines it to be "perhaps the most toxic mushroom known to man", while later studies of toxin concentrations in amanitin-containing mushrooms corroborate this view. The symptoms of poisoning attributed to the mushroom have been noted to be relatively unusual: a local anesthesic effect, "pins and needles" sensation, and nausea without vomiting. Although these clinical symptoms are inconsistent with those of amatoxin poisoning, the presence of α-, β- and γ- amanitins in this species has been verified with chromatographic analysis. Amatoxins damage the liver and kidney by binding irreversibly to RNA polymerase II. Three separate instances of poisoning in Indonesia involved 18 people, 14 of which died. Based on this set of occurrences, death occurs in 7–51 hours "unless the patient survives, which seems to depend on the quantity eaten and the vigor of the individual." Another death attributed to this mushroom was reported in Germany in the early 1980s. Severe poisonings have been treated with complete blood dialysis or liver transplants.
Amanita phalloides
"A. phalloides" is one of the most poisonous of all known toadstools. It is estimated that as little as half a mushroom contains enough toxin to kill an adult human. It has been involved in the majority of human deaths from mushroom poisoning, possibly including the deaths of Roman Emperor Claudius in AD 54 and Holy Roman Emperor Charles VI in 1740. It has been the subject of much research, and many of its biologically active agents have been isolated. The principal toxic constituent is α-amanitin, which damages the liver and kidneys, causing hepatic and renal failure that can be fatal.
Vespa luctuosa
The venom of "Vespa luctuosa" has the highest recorded toxicity to mice of any wasp species tested. The of the venom is 1.6 mg/kg. The toxicity (measured against mice) per weight of "Vespa luctuosa" venom is higher than that of the Japanese giant hornet ("Vespa mandarinia japonica"), which has an LD of 4.0 mg/kg, but which is responsible for many more human deaths than "Vespa luctuosa". The greater lethality of Japanese giant hornet stings—as well as the closely related Asian giant hornet ("Vespa mandarinia")—results from a considerably larger volume of venom being injected per sting.
Botulinum toxin
There are eight types of botulinum toxin, named type A–H. Types A and B are capable of causing disease in humans, and are also used commercially and medically. Types C–G are less common; types E and F can cause disease in humans, while the other types cause disease in other animals. Type H is considered the deadliest substance in the world an injection of only 2 ng can cause death to an adult. Botulinum toxin types A and B are used in medicine to treat various muscle spasms and diseases characterized by overactive muscle. Commercial forms are marketed under the brand names Botox and Dysport, among others.
Cyanotoxin
The toxin was called the Very Fast Death Factor because it induced tremors, paralysis and death within a few minutes when injected into the body cavity of mice. In 1977, the structure of VFDF was determined as a secondary, bicyclic amine alkaloid, and it was renamed anatoxin-"a". Structurally, it is similar to cocaine. There is continued interest in anatoxin-"a" because of the dangers it presents to recreational and drinking waters, and because it is a particularly useful molecule for investigating acetylcholine receptors in the nervous system. The deadliness of the toxin means that it has a high military potential as a toxin weapon.
Clostridium difficile toxin A
TcdA is one of the largest bacterial toxins known. With a molecular mass of 308 kDa, it is usually described as a potent enterotoxin, but it also has some activity as a cytotoxin. The toxin acts by modifying host cell GTPase proteins by glucosylation, leading to changes in cellular activities. Risk factors for "C. difficile" infection include antibiotic treatment, which can disrupt normal intestinal microbiota and lead to colonization of "C. difficile" bacteria.
Botulinum toxin
Botulinum toxin produced by "Clostridium botulinum" is the cause of botulism. Humans most commonly ingest the toxin from eating improperly-canned foods in which "C. botulinum" has grown. However, the toxin can also be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and can cause a condition known as floppy baby syndrome. In all cases, the toxin can then spread, blocking nerves and muscle function. In severe cases, the toxin can block nerves controlling the respiratory system or heart, resulting in death.
Mushroom poisoning
Of the most lethal mushrooms, three—the death cap ("A. phalloides"), destroying angels ("A. virosa" and "A. bisporigera"), and the fool's mushroom ("A. verna")—belong to the genus "Amanita", and two more—the deadly webcap ("C. rubellus"), and the fool's webcap ("C. orellanus")—are from the genus "Cortinarius". Several species of Galerina, Lepiota, and Conocybe also contain lethal amounts of amatoxins. Deadly species are listed in the List of deadly fungi.
Tityustoxin
The crude venom of "T. serrulatus" contains different toxins. Some of the strongest derivates are the neurotoxins tityustoxin and toxin Ts-g. Two types of toxins are considered to be responsible for the main toxic effect: toxin gamma (a β-type toxin) and tityustoxin (TsTX, an α-type toxin), both with a specific affinity to the sodium channel. Other types of venom are: TsTX-kα, a 37 amino acid, toxin gamma (TsTX-γ and TsTX-I) with 61 amino acid residues is the major neurotoxin of this venom. TsTX-Kβ has a longer chain. K+ channels blocking peptides are single chain polypeptides of 30-40 amino acids with three disulphide bridges. The toxin with four disulphide bonds is from TsTX-IV. This contains 41 amino acid residues.Two types of toxin are interesting: α-Scorpion toxins bind at site 3 of Na1 channels, causing a slowing of their inactivation. β-Scorpion toxins bind at site 4, shifting the activation of Na1 currents (INa) toward more negative potentials. Tityustoxin causes cell depolarization, activating Na channels and increasing the Na uptake that can affect Ca uptake and can increase acetylcholine (ACh) release from cerebral cortical slices.
Phalloidin
Phalloidin belongs to a class of toxins called phallotoxins, which are found in the death cap mushroom "(Amanita phalloides)". It is a rigid bicyclic heptapeptide that is lethal after a few days when injected into the bloodstream. The major symptom of phalloidin poisoning is acute hunger due to the destruction of liver cells. It functions by binding and stabilizing filamentous actin (F-actin) and effectively prevents the depolymerization of actin fibers. Due to its tight and selective binding to F-actin, derivatives of phalloidin containing fluorescent tags are used widely in microscopy to visualize F-actin in biomedical research. Though phallotoxins are highly toxic to liver cells, they add little to the toxicity of ingested death cap, as they are not absorbed through the gut.
Metal toxicity
Metal toxicity or metal poisoning is the toxic effect of certain metals in certain forms and doses on life. Some metals are toxic when they form poisonous soluble compounds. Certain metals have no biological role, i.e. are not essential minerals, or are toxic when in a certain form. In the case of lead, any measurable amount may have negative health effects. Often heavy metals are thought as synonymous, but lighter metals may also be toxic in certain circumstances, such as beryllium and lithium. Not all heavy metals are particularly toxic, and some are essential, such as iron. The definition may also include trace elements when in abnormally high doses may be toxic. An option for treatment of metal poisoning may be chelation therapy, which is a technique which involves the administration of chelation agents to remove metals from the body.
Amanita bisporigera
"Amanita bisporigera" is considered the most toxic North American "Amanita" mushroom, with little variation in toxin content between different fruit bodies. Three subtypes of amatoxin have been described: α-, β, and γ-amanitin. The principal amatoxin, α-amanitin, is readily absorbed across the intestine, and 60% of the absorbed toxin is excreted into bile and undergoes enterohepatic circulation; the kidneys clear the remaining 40%. The toxin inhibits the enzyme RNA polymerase II, thereby interfering with DNA transcription, which suppresses RNA production and protein synthesis. This causes cellular necrosis, especially in cells which are initially exposed and have rapid rates of protein synthesis. This process results in severe acute liver dysfunction and, ultimately, liver failure. Amatoxins are not broken down by boiling, freezing, or drying. Roughly 0.2 to 0.4 milligrams of α-amanitin is present in 1 gram of "A. bisporigera"; the lethal dose in humans is less than 0.1 mg/kg body weight. One mature fruit body can contain 10–12 mg of α-amanitin, enough for a lethal dose. The α-amanitin concentration in the spores is about 17% that of the fruit body tissues. "A. bisporigera" also contains the phallotoxin phallacidin, structurally related to the amatoxins but considered less poisonous because of poor absorption. Poisonings (from similar white amanitas) have also been reported in domestic animals, including dogs, cats, and cows.
Greater weever
The potentially lethal protein component in the crude venom of "T. draco" is a 105 kDa polypeptide which is called Dracotoxin. The crude venom of "T. draco" has been shown to have membrane depolarizing and haemolytic characteristics. Those characteristics could be retraced to said single protein component. The depolarisation effect however could not be explained by well-established approaches. Neither does the depolarisation effect take place through Na+ or K+-channels nor through Na+-K+-ATPase activity.⁠
The weever sting is often followed by first ischemic and subsequently hyperemic effects in the tissue surrounding the sting. These effects might be related to the high concentrations of histamines and catecholamines found in the venom.⁠
⁠⁠While Church & Hodgson (2002) suggest a cholinesterase activity of the toxin itself, Haavaldsen & Fonnum (1963) interpreted their finding of a high concentration of cholinesterase in the venom as a sign for a cholinergic mechanism in the production of the venom because cholinesterase activity hasn’t yet been described in the venoms of the animal kingdom.⁠ 
As Russel & Emery (1960) stated, the toxin extract of "T. draco" has a greyish colour but is clear in its appearance. It is said to have a “fishy taste” and “ammoniacal odor”. The pH value of the extract seems to be 6.78 and is with that slightly sour.⁠
The toxin of the closely related lesser weever T. vipera has been shown to contain 5-Hydroxy-Triptamine also called Serotonin but in the toxin of "T. draco" this finding could not be confirmed⁠.⁠
The toxicity of the venom was dependent on the way of extraction. The highest toxicity was measured in live fish which were shock frozen and laired in −70 °C-freezers. Under such conditions the minimal lethal dose for mice was 1.8 μg/g while at least 110 mg could be extracted from an average sized fish.⁠
Acute toxicity
Limits for short-term exposure, such as STELs or CVs, are defined only if there is a particular acute toxicity associated with a substance. These limits are set by the American Conference of Governmental Industrial Hygienists (ACGIH) and the Occupational Safety and Health Administration (OSHA), based on experimental data. The values set by these organizations do not always coincide exactly, and in the chemical industry it is general practice to choose the most conservative value in order to ensure the safety of employees. The values can typically be found in a material safety data sheet. There are also different values based on the method of entry of the compound (oral, dermal, or inhalation).The most referenced value in the chemical industry is the median lethal dose, or LD50. This is the concentration of substance which resulted in the death of 50% of test subjects (typically mice or rats) in the laboratory.
Tetryl
Although tetryl is among the most toxic explosive compounds, it is very short-lived. This combined with the fact that the health impacts of this compound are largely unstudied, not much is known about any health problems that this compound may cause.
Alternaria brassicicola
The most common toxin studied for "A. brassicicola" is the AB toxin, said to be connected to the virulence, pathogenicity and host range for the fungus. It is most likely produced during conidial germination and probably linked to the ability of the fungus to infect and colonize Brassica leaves However, recent studies have explored new potential metabolites. For example, this fungus also produces histone deacetylase inhibitors, but these do not have a significant impact on lesion size. Some studies show only a 10% reduction in virulence. Furthermore, alternariol and tenuazonic acid seem to affect mitochondrial-mediated apoptosis pathways and protein synthesis respectively (in the host cell), but again, not to a significant degree. Some cytokines have been linked with the discolouration associated with "A. brassicicola" infection. Cell wall degrading enzymes like lipases and cutinases are also linked to its pathogenicity, but more evidence of their efficacy is required. One important transcription factor is AbPf2. It regulates 6 of the 139 genes encoding small secretion proteins and may have a role in pathogenesis, specifically cellulose digestion.
Ricin
Ricin ( ), a lectin (a carbohydrate-binding protein) produced in the seeds of the castor oil plant, "Ricinus communis", is a highly potent toxin. A dose of purified ricin powder the size of a few grains of table salt can kill an adult human. The median lethal dose (LD) of ricin is around 22 micrograms per kilogram of body weight if the exposure is from injection or inhalation (1.78 milligrams for an average adult). Oral exposure to ricin is far less toxic as some of the poison is inactivated in the stomach. An estimated lethal oral dose in humans is approximately 1 milligram per kilogram.
Chironex fleckeri
Researchers at the University of Hawaii's Department of Tropical Medicine have found that the venom causes cells to become porous enough to allow potassium leakage, causing hyperkalemia which can lead to cardiovascular collapse and death as quickly as within two to five minutes with an LD50 of 0.04 mg/kg, making it the most venomous jellyfish in the world (to laboratory mice). It was postulated that a zinc compound may be developed as an antidote. Occasionally, swimmers who get stung will undergo cardiac arrest or drown before they can even get back to the shore or boat.
Crotalus tigris
Although tiger rattlesnakes are reluctant to strike, they are highly venomous and cantankerous, so pose a potential threat to humans. Their venom contains a neurotoxin and a myotoxin known to cause muscle necrosis. Although production is low compared to other rattlesnakes, their venom is the third most toxic of any snake in the Western Hemisphere. The combination of toxins in their venom makes them extremely dangerous to humans.
List of dangerous snakes
The Asian Monocled cobra ("Naja kaouthia") is a medically important species as it is responsible for a considerable amount of bites throughout its range. The major toxic components in the Monocled cobras venom are postsynaptic neurotoxins, which block the nerve transmission by binding specifically to the nicotinic acetylcholine receptor, leading to flaccid paralysis and even death by respiratory failure. The major α-neurotoxin in "Naja kaouthia" venom is a long neurotoxin, α-cobratoxin; the minor α-neurotoxin is different from cobrotoxin in one residue. The neurotoxins of this particular species are weak. The venom of this species also contains myotoxins and cardiotoxins. The median lethal dose () is 0.28-0.33 mg per gram of mouse body weight. In case of IV the is 0.373 mg/kg, and 0.225 mg/kg in case of IP. The average venom yield per bite is approximately 263 mg (dry weight). The monocled cobra causes the highest fatality due to snake venom poisoning in Thailand.
Envenomation usually presents predominantly with extensive local necrosis and systemic manifestations to a lesser degree. Drowsiness, neurological and neuromuscular symptoms will usually manifest earliest; hypotension, flushing of the face, warm skin, and pain around bite site typically manifest within one to four hours following the bite; paralysis, ventilatory failure or death could ensue rapidly, possibly as early as 60 minutes in very severe cases of envenomation. However, the presence of fang marks does not always imply that envenomation actually occurred.
Neutron poison
Xenon-135 in particular tremendously affects the operation of a nuclear reactor because it is the most powerful known neutron poison. The inability of a reactor to be restarted due to the buildup of xenon-135 (reaches a maximum after about 10 hours) is sometimes referred to as "xenon precluded start-up". The period of time in which the reactor is unable to override the effects of xenon-135 is called the "xenon dead time" or "poison outage". During periods of steady state operation, at a constant neutron flux level, the xenon-135 concentration builds up to its equilibrium value for that reactor power in about 40 to 50 hours. When the reactor power is increased, xenon-135 concentration initially decreases because the burn up is increased at the new, higher power level. Thus, the dynamics of xenon poisoning are important for the stability of the flux pattern and geometrical power distribution, especially in physically large reactors.
Conus geographus
The geography cone is highly dangerous; live specimens should be handled with extreme caution. "C. geographus" has the most toxic sting known among "Conus" species and is responsible for more than thirty human fatalities. Yoshiba estimated an LD70 value (in humans) of 0.001-0.003 mg/kg. In two cases of envenomation, only 0.0002-0.0005 mg resulted in severe paralysis. Other figures estimate LD50 values of 0.012-0.03 mg/kg. These estimates make the geographic cone snail the most venomous animal in the world. The venom is a complex mix of hundreds of different toxins that is delivered through toxoglossan radula, a harpoon-like tooth propelled from an extendable proboscis. There is no antivenom for a cone snail sting, and treatment consists of keeping victims alive until the toxins wear off.
Among the compounds found in cone snail venom are proteins which, when isolated, have great potential as pain-killing drugs. Research shows that certain component proteins of the venom target specific human pain receptors and can be up to 10,000 times more potent than morphine without morphine's addictive properties and side-effects.
Toxin
A toxin (from ) is a poisonous substance produced within living cells or organisms; synthetic toxicants created by artificial processes are thus excluded. The term was first used by organic chemist Ludwig Brieger (1849–1919).
SNARE (protein)
Botulinum Toxin (BoNT) is one of the most potent toxins to have ever been discovered. It is a proteolytic enzyme that cleaves SNARE proteins in neurons. Its protein structure is composed of two peptide subunits, a heavy chain (100kDas) and a light chain (50kDas), which are held together by a disulfide bond. The action of BoNT follows a 4-step mechanism including binding to the neuronal membrane, endocytosis, membrane translocation, and proteolysis of SNARE proteins.
Heavy metals
Heavy metals essential for life can be toxic if taken in excess; some have notably toxic forms. Vanadium pentoxide (VO) is carcinogenic in animals and, when inhaled, causes DNA damage. The purple permanganate ion MnO is a liver and kidney poison. Ingesting more than 0.5 grams of iron can induce cardiac collapse; such overdoses most commonly occur in children and may result in death within 24 hours. Nickel carbonyl (Ni(CO)), at 30 parts per million, can cause respiratory failure, brain damage and death. Imbibing a gram or more of copper sulfate (CuSO) can be fatal; survivors may be left with major organ damage. More than five milligrams of selenium is highly toxic; this is roughly ten times the 0.45 milligram recommended maximum daily intake; long-term poisoning can have paralytic effects.
Clostridium histolyticum
The alpha-toxin is the major toxigenic factor of "C. histolyticum". When injected into muscle, it can cause death in laboratory animals within hours. Alpha-toxin is a necrotizing, but not hemolytic, toxin. This toxin is secreted, as it is isolated from filtrates of "C. histolyticum" cultures. It is neutralized by antisera produced against toxic filtrates of "C. septicum" cultures through cross-neutralization. Additionally, alpha-toxin is readily inactivated by proteolytic enzymes. It has been shown that only about 29% of "C. histolyticum" strains isolated from soil actually produce this alpha-toxin.
Delphinium barbeyi
All members of the "Delphinium" genus are toxic to humans and livestock. Many species of larkspurs are known for being poisonous, and as hazards to livestock. This species is notorious as one of the toxic plants most commonly responsible for livestock death, especially cattle fatalities on the rangelands of Colorado and Utah. Sheep are much less susceptible. Up to 15% of a cow herd can be lost to poisoning in areas where this larkspur and its hybrids are common. The cost to ranchers is in the millions of dollars. Abundance of larkspur has persuaded ranchers to remove their animals from some areas of rangeland, or use the land only at certain times of the year. The plant contains many toxic alkaloids. The alkaloids barbinine and barbinidine were first isolated from this species. The most hazardous are called methyl succidimido anthramoyl lycoctomine (MSAL) diterpenoids. About two kilograms dry weight of the plant is estimated to provide a fatal dose of alkaloid. Paralysis occurs and death is caused by respiratory paralysis. Toxicity reactions in animals, sometimes called larkspur toxicosis, can be treated with physostigmine.
Ricin
Ricin is several orders of magnitude less toxic than botulinum or tetanus toxin, but the latter are harder to come by. Compared to botulinum or anthrax as biological weapons or chemical weapons, the quantity of ricin required to achieve LD over a large geographic area is significantly more than an agent such as anthrax (tons of ricin vs. only kilogram quantities of anthrax). Ricin is easy to produce, but is not as practical or likely to cause as many casualties as other agents. Ricin is easily denatured by temperatures over meaning many methods of deploying ricin would generate enough heat to denature it. Once deployed, an area contaminated with ricin remains dangerous until the bonds between chain A or B have been broken, a process that takes two or three days. In contrast, anthrax spores may remain lethal for decades. Jan van Aken, a German expert on biological weapons, explained in a report for The Sunshine Project that Al Qaeda’s experiments with ricin suggest their inability to produce botulinum or anthrax.
Microbial toxin
"Botulinum" neurotoxins (BoNTs) are the causative agents of the deadly food poisoning disease botulism, and could pose a major biological warfare threat due to their extreme toxicity and ease of production. They also serve as powerful tools to treat an ever expanding list of medical conditions.
Anthrax
The lethality of the anthrax disease is due to the bacterium's two principal virulence factors: the poly-D-glutamic acid capsule, which protects the bacterium from phagocytosis by host neutrophils, and the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: protective antigen (PA), edema factor (EF), and lethal factor (LF). PA plus LF produces lethal toxin, and PA plus EF produces edema toxin. These toxins cause death and tissue swelling (edema), respectively.
Dortoxin
Injection of pure dortoxin in mice leads to hyperactivity, tremors, convulsions, profuse salivation, lacrimation, continuous urination and vocalizations. The toxin has a rapid onset. The last period of hyperactivity is more intense and leads to death, after which postmortem twitching occurs for at least 30 seconds. The toxin is lethal at 200 ng of peptide in a 20 g mouse.
Mercury poisoning
Compounds of mercury tend to be much more toxic than either the elemental form or the salts. These compounds have been implicated in causing brain and liver damage. The most dangerous mercury compound, dimethylmercury, is so toxic that even a few microliters spilled on the skin, or even on a latex glove, can cause death.
Destruction of chemical weapons
If the precautions would somehow fail, human exposure to chemical agents can result in a variety of consequences varying anywhere from mild effects such as minor discomfort to as serious effects, such as death, depending on the agent and dosage. The dosages that humans intake are measured in mg-min/m. Of the critical three agents, mustard is the least lethal while VX is the most lethal.
Mustard is a blistering agent that works to destroy different substances with cells of living tissue. Effects of exposure typically appear within a day. While acute mortality is low, death can occur from long term complications. Humans exposed to a non-disabling dose of 12 mg-min/m will have signs of mild discomfort and conjunctival injection. With a more disabling dose of 60 mg-min/m, humans will experience generalized conjunctivas, edema, photophobia and eye irritation. For a lethal dose, the agent would have to be extremely concentrated as 1500 mg-min/m give a 50 percent lethality rate.
GB or Sarin is the least lethal of the nerve agents. Nerve agents act to disable enzymes responsible for transmitting nerve impulses. Initial effects can appear almost immediately after exposure and can cause death within minutes. Humans exposed to a non-disabling dose which would be about .05 mg/m for twenty minutes, can experience headaches, eye pain, tightness in chest, rhino rhea, cramps, nausea, malaise and miosis. With a slightly more potent dose of .05 mg/m for 30 minutes effects include inhibition, dyspnea and SFEMG changes. The required dose for a rate of 50 percent lethality is 70 mg-min/m. VX is also another nerve agent like GB but is much more lethal. At the non-disabling and disabling levels, VX causes the same effects as GB but at much lower doses, 12 times less than that of GB. Also, a mere 30 mg-min/m will give a death rate of 50 percent.
Hemotoxin
Hemotoxins, haemotoxins or hematotoxins are toxins that destroy red blood cells (that is, cause haemotoxin), 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.
Polychlorinated dibenzodioxins
2,3,7,8-Tetrachlorodibenzodioxin (TCDD) is considered the most toxic of the congeners (for the mechanism of action, see 2,3,7,8-Tetrachlorodibenzodioxin and Aryl hydrocarbon receptor). Other dioxin congeners including PCDFs and PCBs with dioxin-like toxicity, are given a toxicity rating from 0 to 1, where TCDD = 1 (see Dioxins and dioxin-like compounds). This toxicity rating is called the Toxic Equivalence Factor concept, or TEF. TEFs are consensus values and, because of the strong species dependence for toxicity, are listed separately for mammals, fish, and birds. TEFs for mammalian species are generally applicable to human risk calculations. The TEFs have been developed from detailed assessment of literature data to facilitate both risk assessment and regulatory control. Many other compounds may also have dioxin-like properties, particularly non-ortho PCBs, one of which has a TEF as high as 0.1.
Amanita phalloides
As the common name suggests, the fungus is highly toxic, and is responsible for the majority of fatal mushroom poisonings worldwide. Its biochemistry has been researched intensively for decades, and , or half a cap, of this mushroom is estimated to be enough to kill a human. In 2006, a family of three in Poland was poisoned, resulting in one death and the two survivors requiring liver transplants. In 2017, 14 people in California were poisoned, including an 18 month old who required a liver transplant. Some authorities strongly advise against putting suspected death caps in the same basket with fungi collected for the table and to avoid even touching them. Furthermore, the toxicity is not reduced by cooking, freezing, or drying.
Cytolysin
The term "Cytolysin" or "Cytolytic toxin" was first introduced by Alan Bernheimer to describe membrane damaging toxins (MDTs) that have cytolytic effects to cells. The first kind of cytolytic toxin discovered have hemolytic effects on erythrocytes of certain sensitive species, such as Human. For this reason "Hemolysin" was first used to describe any MDTs. In the 1960s certain MDTs were proved to be destructive on cells other than erythrocytes, such as leukocytes. The term "Cytolysin" is then introduced by Bernheimer to replace "Hemolysin". Cytolysins can destruct membranes without creating lysis to cells. Therefore, "membrane damaging toxins" (MDTs) describes the essential actions of cytolysins. Cytolysins comprise more than 1/3 of all bacterial protein toxins. Bacterial protein toxins can be highly poisonous to human. For example, "Botulinum" is 3x10 more toxic than snake venom to human and its toxic dose is only 0.8x10 mg. A wide variety of gram-positive and gram-negative bacteria use cytolysin as their primary weapon for creating diseases, such as "Clostridium perfringens" and "Staphylococcus".
Cll2
Cll2 belongs to the beta-type of sodium channel-inhibiting scorpion toxins. The Cll venom consists of six fractions, of which only Cll2 is lethal, amounting to ~42% of the venom. Cll2 consists of thirteen sub-fractions, of which sub-fraction 9 is the largest. The molecular weight of Cll2 is about 7600 Da. The primary structure of the Cll2 toxin (toxin II.9) is: 
Like other scorpion beta toxins (beta-ScTxs), Cll2 targets voltage-gated sodium channels (VGSCs). It specifically binds to and alters the Na1.6 channel, as well as, but to a lesser extent, other Nav isoforms. It binds to the extracellular end of the ISS4 (loop between the third and fourth segment) voltage sensor and locks it in the activated outward position. This binding location is commonly referred to as VGSC site 4.
Pulmonary toxicity
Pulmonary toxicity is possible due to many chemical compounds. However, the most famous (infamous) example is pulmonary toxicity due to asbestos. Asbestos can lead to a highly dangerous (i.e., highly malignant) lung cancer called malignant pleural mesothelioma, sometimes also simply called mesothelioma. As a consequence, the use of asbestos is now completely prohibited by law in most countries.
Botulinum toxin
In 1820, Justinus Kerner, a small-town German medical officer and romantic poet, gave the first complete description of clinical botulism based on extensive clinical observations of so-called “sausage poisoning”. Following experiments on animals and on himself, he concluded that the toxin acts by interrupting signal transmission in the somatic and autonomic motor systems, without affecting sensory signals or mental functions. He observed that the toxin develops under anaerobic conditions, and can be lethal in minute doses. His prescience in suggesting that the toxin might be used therapeutically earned him recognition as the pioneer of modern botulinum toxin therapy.
Rotenone
Rotenone is classified by the World Health Organization as moderately hazardous. It is mildly toxic to humans and other mammals, but extremely toxic to insects and aquatic life, including fish. This higher toxicity in fish and insects is because the lipophilic rotenone is easily taken up through the gills or trachea, but not as easily through the skin or the gastrointestinal tract. Rotenone is toxic to erythrocytes "in vitro".
Clostridium enterotoxin
Clostridial species are one of the major causes of food poisoning/gastrointestinal illnesses. They are anaerobic, gram-positive, spore-forming rods that occur naturally in the soil. Among the family are: "Clostridium botulinum", which produces one of the most potent toxins in existence; "Clostridium tetani", causative agent of tetanus; and "Clostridium perfringens", commonly found in wound infections and diarrhea cases. The use of toxins to damage the host is a method deployed by many bacterial pathogens.
Median lethal dose
In toxicology, the median lethal dose, LD (abbreviation for "lethal dose, 50%"), LC (lethal concentration, 50%) or LCt is a measure of the lethal dose of a toxin, radiation, or pathogen. The value of LD for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD is indicative of increased toxicity.
Deathstalker
The deathstalker is one of the most dangerous species of scorpions. Its venom is a powerful mixture of neurotoxins, with a low lethal dose. While a sting from this scorpion is extraordinarily painful, it normally would not kill a healthy adult human. However, young children, the elderly, or infirm (such as those with a heart condition and those who are allergic) are at much greater risk. Any envenomation runs the risk of anaphylaxis, a potentially life-threatening allergic reaction to the venom. A study from Israel shows a high rate of pancreatitis following envenomation. If a sting from "Leiurus quinquestriatus" does prove deadly, the cause of death is usually pulmonary edema.
Sierra newt
Like other genus "Taricha" members, the glands in the skin of "Taricha sierrae" secrete the potent neurotoxin tetrodotoxin, which is hundreds of times more toxic than cyanide. This is the same toxin found in pufferfish and harlequin frogs. Researchers believe bacteria synthesize tetrodotoxin, and the animals that employ the neurotoxin acquire it through consumption of these bacteria. This neurotoxin is strong enough to kill most vertebrates, including humans. However, it is dangerous only if ingested.