Median lethal dose

In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a measure of the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of increased toxicity.

The test was created by J.W. Trevan in 1927.[1] The term semilethal dose is occasionally used in the same sense, in particular with translations of foreign language text, but can also refer to a sublethal dose. LD50 is usually determined by tests on animals such as laboratory mice. In 2011, the U.S. Food and Drug Administration approved alternative methods to LD50 for testing the cosmetic drug Botox without animal tests.[2][3]

Conventions

The LD50 is usually expressed as the mass of substance administered per unit mass of test subject, typically as milligrams of substance per kilogram of body mass, sometimes also stated as nanograms (suitable for botulinum), micrograms, or grams (suitable for paracetamol) per kilogram. Stating it this way allows the relative toxicity of different substances to be compared, and normalizes for the variation in the size of the animals exposed (although toxicity does not always scale simply with body mass). For substances in the environment, such as poisonous vapors or substances in water that are toxic to fish, the concentration in the environment (per cubic metre or per litre) is used, giving a value of LC50. But in this case, the exposure time is important (see below).

The choice of 50% lethality as a benchmark avoids the potential for ambiguity of making measurements in the extremes and reduces the amount of testing required. However, this also means that LD50 is not the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than the LD50. Measures such as "LD1" and "LD99" (dosage required to kill 1% or 99%, respectively, of the test population) are occasionally used for specific purposes.[4]

Lethal dosage often varies depending on the method of administration; for instance, many substances are less toxic when administered orally than when intravenously administered. For this reason, LD50 figures are often qualified with the mode of administration, e.g., "LD50 i.v."

The related quantities LD50/30 or LD50/60 are used to refer to a dose that without treatment will be lethal to 50% of the population within (respectively) 30 or 60 days. These measures are used more commonly within Radiation Health Physics, as survival beyond 60 days usually results in recovery.

A comparable measurement is LCt50, which relates to lethal dosage from exposure, where C is concentration and t is time. It is often expressed in terms of mg-min/m3. ICt50 is the dose that will cause incapacitation rather than death. These measures are commonly used to indicate the comparative efficacy of chemical warfare agents, and dosages are typically qualified by rates of breathing (e.g., resting = 10 l/min) for inhalation, or degree of clothing for skin penetration. The concept of Ct was first proposed by Fritz Haber and is sometimes referred to as Haber's Law, which assumes that exposure to 1 minute of 100 mg/m3 is equivalent to 10 minutes of 10 mg/m3 (1 × 100 = 100, as does 10 × 10 = 100).

Some chemicals, such as hydrogen cyanide, are rapidly detoxified by the human body, and do not follow Haber's Law. So, in these cases, the lethal concentration may be given simply as LC50 and qualified by a duration of exposure (e.g., 10 minutes). The Material Safety Data Sheets for toxic substances frequently use this form of the term even if the substance does follow Haber's Law.

For disease-causing organisms, there is also a measure known as the median infective dose and dosage. The median infective dose (ID50) is the number of organisms received by a person or test animal qualified by the route of administration (e.g., 1,200 org/man per oral). Because of the difficulties in counting actual organisms in a dose, infective doses may be expressed in terms of biological assay, such as the number of LD50's to some test animal. In biological warfare infective dosage is the number of infective doses per cubic metre of air times the number of minutes of exposure (e.g., ICt50 is 100 medium doses - min/m3).

Limitation

As a measure of toxicity, LD50 is somewhat unreliable and results may vary greatly between testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration.[5]

There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans (cf. paracetamol toxicity), and vice versa. For example, chocolate, comparatively harmless to humans, is known to be toxic to many animals. When used to test venom from venomous creatures, such as snakes, LD50 results may be misleading due to the physiological differences between mice, rats, and humans. Many venomous snakes are specialized predators on mice, and their venom may be adapted specifically to incapacitate mice; and mongooses may be exceptionally resistant. While most mammals have a very similar physiology, LD50 results may or may not have equal bearing upon every mammal species, such as humans, etc.

Examples

Note: Comparing substances (especially drugs) to each other by LD50 can be misleading in many cases due (in part) to differences in effective dose (ED50). Therefore, it is more useful to compare such substances by therapeutic index, which is simply the ratio of LD50 to ED50.

The following examples are listed in reference to LD50 values, in descending order, and accompanied by LC50 values, {bracketed}, when appropriate.

Substance Animal, Route LD50
{LC50}
LD50 : g/kg
{LC50 : g/L}
standardized
Reference
Water rat, oral >90,000 mg/kg >90 [6]
Sucrose (table sugar) rat, oral 29,700 mg/kg 29.7 [7]
Glucose (blood sugar) rat, oral 25,800 mg/kg 25.8 [8]
Monosodium glutamate (MSG) rat, oral 16,600 mg/kg 16.6 [9]
Stevioside (from stevia) mice and rats, oral >15,000 mg/kg >15 [10]
Vitamin C (ascorbic acid) rat, oral 11,900 mg/kg 11.9 [11]
Glyphosate (isopropylamine salt of) rat, oral 10,537 mg/kg 10.537 [12]
Lactose (milk sugar) rat, oral >10,000 mg/kg >10 [13]
Aspartame mice, oral >10,000 mg/kg >10 [14]
Urea rat, oral 8,471 mg/kg 8.471 [15]
Cyanuric acid rat, oral 7,700 mg/kg 7.7 [16]
Cadmium sulfide rat, oral 7,080 mg/kg 7.08 [17]
Ethanol (Grain alcohol) rat, oral 7,060 mg/kg 7.06 [18]
Sodium isopropyl methylphosphonic acid (IMPA, metabolite of sarin) rat, oral 6,860 mg/kg 6.86 [19]
Melamine rat, oral 6,000 mg/kg 6 [16]
Methanol rat, oral 5,628 mg/kg 5.628 [20]
Taurine rat, oral >5,000 mg/kg >5 [21]
Melamine cyanurate rat, oral 4,100 mg/kg 4.1 [16]
Fructose (fruit sugar) rat, oral 4,000 mg/kg 4 [22]
Sodium molybdate rat, oral 4,000 mg/kg 4 [23]
Sodium chloride (table salt) rat, oral 3,000 mg/kg 3 [24]
Paracetamol (acetaminophen) mouse, oral 338 mg/kg 0.338 [25]
Delta-9-tetrahydrocannabinol (THC) rat, oral 1270 mg/kg 1.27 [26]
Cannabidiol (CBD) rat, oral 980 mg/kg 0.98 [27]
Metallic Arsenic rat, oral 763 mg/kg 0.763 [28]
Ibuprofen rat, oral 636 mg/kg 0.636 [29]
Formaldehyde rat, oral 600–800 mg/kg 0.6 [30]
Solanine main alkaloid in the several plants in Solanaceae amongst them Solanum tuberosum rat, oral (2.8 mg/kg human, oral) 590 mg/kg 0.590 [31]
Alkyl dimethyl benzalkonium chloride (ADBAC) rat, oral
fish, immersion
aquatic invertebrates, immersion
304.5 mg/kg
{0.28 mg/L}
{0.059 mg/L}
0.3045
{0.00028}
{0.000059}
[32]
Coumarin (benzopyrone, from Cinnamomum aromaticum and other plants) rat, oral 293 mg/kg 0.293 [33]
Psilocybin (from magic mushrooms) mouse, oral 280 mg/kg 0.280 [34]
Hydrochloric acid rat, oral 238–277 mg/kg 0.238 [35]
Ketamine rat, intraperitoneal 229 mg/kg 0.229 [36]
Aspirin (acetylsalicylic acid) rat, oral 200 mg/kg 0.2 [37]
Caffeine rat, oral 192 mg/kg 0.192 [38]
Arsenic trisulfide rat, oral 185–6,400 mg/kg 0.185–6.4 [39]
Sodium nitrite rat, oral 180 mg/kg 0.18 [40]
Methylenedioxymethamphetamine (MDMA, ecstasy) rat, oral 160 mg/kg 0.18 [41]
Uranyl acetate dihydrate mouse, oral 136 mg/kg 0.136 [42]
Dichlorodiphenyltrichloroethane (DDT) mouse, oral 135 mg/kg 0.135 [43]
Uranium mice, oral 114 mg/kg (estimated) 0.114 [44]
Bisoprolol mouse, oral 100 mg/kg 0.1 [45]
Cocaine mouse, oral 96 mg/kg 0.096 [46]
Cobalt(II) chloride rat, oral 80 mg/kg 0.08 [47]
Cadmium oxide rat, oral 72 mg/kg 0.072 [48]
Thiopental sodium (used in lethal injection) rat, oral 64 mg/kg 0.064 [49]
Methamphetamine rat, intraperitoneal 57 mg/kg 0.057 [50]
Sodium fluoride rat, oral 52 mg/kg 0.052 [51]
Pentaborane human, oral <50 mg/kg <0.05 [52]
Capsaicin mouse, oral 47.2 mg/kg 0.0472 [53]
Mercury(II) chloride rat, dermal 41 mg/kg 0.041 [54]
Vitamin D3 (cholecalciferol) rat, oral 37 mg/kg 0.037 [55]
Piperidine (from black pepper) rat, oral 30 mg/kg 0.030 [56]
Heroin (diamorphine) mouse, intravenous 21.8 mg/kg 0.0218 [57]
Lysergic acid diethylamide (LSD) rat, intravenous 16.5 mg/kg 0.0165 [58]
Arsenic trioxide rat, oral 14 mg/kg 0.014 [59]
Metallic Arsenic rat, intraperitoneal 13 mg/kg 0.013 [60]
Nicotine human, oral

mice, oral

6.5–13 mg/kg (estimated)

3.34 mg/kg

0.0065–0.013

0.0034

[61]

[62]

Sodium cyanide rat, oral 6.4 mg/kg 0.0064 [63]
Hydrogen cyanide mouse, oral 3.7 mg/kg 0.0037 [64]
Chlorotoxin (CTX, from scorpions) mice 4.3 mg/kg 0.0043 [65]
Carfentanil rat, intravenous 3.39 mg/kg 0.00339 [66]
White phosphorus rat, oral 3.03 mg/kg 0.00303 [67]
Strychnine human, oral 1–2 mg/kg (estimated) 0.001–0.002 [68]
Cantharidin (from blister beetles) human, oral 500 µg/kg 0.0005
Aflatoxin B1 (from Aspergillus flavus mold) rat, oral 480 µg/kg 0.00048 [69]
Plutonium dog, intravenous 320 µg/kg 0.00032 [70]
Amatoxin (from Amanita phalloides mushrooms) rat 300-700 µg/kg 0.0007 [71]
Tetrodotoxin (TTX, from blue-ringed octopus) mice, oral 334 µg/kg 0.000334 [72]
Fentanyl monkey 300 µg/kg 0.0003 [73]
Bufotoxin (from Bufo toads) cat, intravenous 300 µg/kg 0.0003 [74]
Sarin mouse, subcutaneous injection 172 µg/kg 0.000172 [75]
Robustoxin (from Sydney funnel-web spider) mice 150 µg/kg 0.000150 [76]
VX human, oral, inhalation, absorption through skin/eyes 140 µg/kg (estimated) 0.00014 [77]
Venom of the Brazilian wandering spider rat, subcutaneous 134 µg/kg 0.000134 [78]
Aconitine main alkaloid in Aconitum napellus and related species rat, intraveneous 80 µg/kg 0.000080 [79]
Venom of the Inland Taipan (Australian snake) rat, subcutaneous 25 µg/kg 0.000025 [80]
Ricin (from castor oil plant) rat, intraperitoneal
rat, oral
22 μg/kg
20–30 mg/kg
0.000022
0.02
[81]
2,3,7,8-Tetrachlorodibenzodioxin (TCDD, in Agent Orange) rat, oral 20 µg/kg 0.00002
CrTX-A (from box jellyfish venom) crayfish, intraperitoneal 5 µg/kg 0.000005 [82]
Latrotoxin (from widow spider venom) mice 4.3 µg/kg 0.0000043 [83]
Batrachotoxin (from poison dart frog) human, sub-cutaneous injection 2–7 µg/kg (estimated) 0.000002 [84]
Abrin (from rosary pea) mice, intravenously

human, inhalation

human, oral

0.7 µg/kg

3.3 µg/kg

10–1000 µg/kg

0.0000007

0.0000033

0.00001–0.001

Maitotoxin (from ciguateric fish) mouse, intraperitoneal 130 ng/kg 0.00000013 [85]
Polonium-210 human, inhalation 10 ng/kg (estimated) 0.00000001 [86]
Diphtheria toxin mice 10 ng/kg 0.00000001 [87]
Shiga toxin (from dysentery) mice 2 ng/kg 0.000000002 [87]
Tetanospasmin (tetanus toxin) mice 2 ng/kg 0.000000002 [87]
Botulinum toxin (Botox) human, oral, injection, inhalation 1 ng/kg (estimated) 0.000000001 [88]
Ionizing radiation human, irradiation 5 Gy [89]

Animal rights concerns

Animal-rights and animal-welfare groups, such as Animal Rights International,[90] have campaigned against LD50 testing on animals. Several countries, including the UK, have taken steps to ban the oral LD50, and the Organisation for Economic Co-operation and Development (OECD) abolished the requirement for the oral test in 2001 (see Test Guideline 401, Trends in Pharmacological Sciences Vol 22, February 22, 2001).

See also

Other measures of toxicity

Related measures

References

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External links

Acute toxicity

Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as acute toxicity, the adverse effects should occur within 14 days of the administration of the substance.Acute toxicity is distinguished from chronic toxicity, which describes the adverse health effects from repeated exposures, often at lower levels, to a substance over a longer time period (months or years).

It is widely considered unethical to use humans as test subjects for acute (or chronic) toxicity research. However, some information can be gained from investigating accidental human exposures (e.g., factory accidents). Otherwise, most acute toxicity data comes from animal testing or, more recently, in vitro testing methods and inference from data on similar substances.

Dose

Dose means quantity (in units of energy/mass) in the fields of nutrition, medicine, and toxicology. Dosage is the rate of application of a dose, although in common and imprecise usage, the words are sometimes used synonymously.

Dose can also mean quantity (in units of number/area) in the fields of surface science and ion implantation. See the definition of dose in ISO18115-1, term 4.173 (and compare the related definition of fluence in term 4.217 of the same Standard).

Particular uses in this context including:

Dose (biochemistry), the quantity of something that may be eaten by or administered to an organism, or that an organism may be exposed to

Overdose, intaking more than your required dose.

Absorbed dose, an amount of radiation received

Defined daily dose, a World Health Organization statistical measure of drug consumption

Dosage form, a mixture of active and inactive components used to administer a medication

Dose profile, taken by a radiation detector in order to characterise the radiation beams from medical linear accelerators

Dosing, the process of administering a measured amount of a medicine or chemical to an inanimate object or non-human animal

Effective dose (pharmacology), the amount of a substance required to produce an effect on a predefined percentage of a population

Equivalent dose, a measure of radiation dosage to tissue

Maximum tolerated dose, the highest dose of a radiological or pharmacological treatment that will produce the desired effect without unacceptable toxicity

Median lethal dose, is the dose of a toxic substance or radiation required to kill half the members of a tested population after a specified test duration

Optimal Biological Dose, the quantity of a radiological or pharmacological treatment that will produce the desired effect with acceptable toxicity

Physiologic dose, within the range of concentrations or potencies that would occur naturally

Reference dose, the United States Environmental Protection Agency's maximum acceptable oral dose of a toxic substance

IC50

The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function.

This quantitative measure indicates how much of a particular drug or other substance (inhibitor) is needed to inhibit a given biological process (or component of a process, i.e. an enzyme, cell, cell receptor or microorganism) by half. The values are typically expressed as molar concentration.

It is commonly used as a measure of antagonist drug potency in pharmacological research. According to the FDA, IC50 represents the concentration of a drug that is required for 50% inhibition in vitro. It is comparable to an EC50 for agonist drugs. EC50 also represents the plasma concentration required for obtaining 50% of a maximum effect in vivo.

Inland taipan

The inland taipan (Oxyuranus microlepidotus), also commonly known as the western taipan, the small-scaled snake, or the fierce snake, is an extremely venomous snake of the taipan (Oxyuranus) genus, and is endemic to semi-arid regions of central east Australia. Aboriginal Australians living in those regions named the snake Dandarabilla. It was first described by Frederick McCoy in 1879 and then by William John Macleay in 1882, but for the next 90 years, it was a mystery species to the scientific community. No more specimens were found, and virtually nothing was added to the knowledge of this species until its rediscovery in 1972.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.Although extremely venomous and a capable striker, in contrast to the rather aggressive coastal taipan, the inland taipan is usually quite a shy and reclusive snake, with a placid disposition, and prefers to escape from trouble. However, it will defend itself and strike if provoked, mishandled, or prevented from escaping. Because it lives in such remote locations, the inland taipan seldom comes in contact with people; therefore it is not considered the most deadly snake in the world overall, especially in terms of disposition and human deaths per year. The word "fierce" from its alternative name describes its venom, not its temperament.

LD50 (disambiguation)

LD50 is the median lethal dose in toxicology.

LD50 may also refer to:

L.D. 50 (album), an album by Mudvayne

LD 50 Lethal Dose, a 2003 UK film

"LD50", an episode of NCIS: Los Angeles

Lethal dose

In toxicology, the lethal dose (LD) is an indication of the lethal toxicity of a given substance or type of radiation. Because resistance varies from one individual to another, the "lethal dose" represents a dose (usually recorded as dose per kilogram of subject body weight) at which a given percentage of subjects will die. The lethal concentration is a lethal dose measurement used for gases or particulates. The LD may be based on the standard person concept, a theoretical individual that has perfectly "normal" characteristics, and thus not apply to all sub-populations.

List of highly toxic gases

Many gases have toxic properties, which are often assessed using the LC50 (median lethal dose) measure. In the United States, many of these gases have been assigned an NFPA 704 health rating of 4 (may be fatal) or 3 (may cause serious or permanent injury), and/or exposure limits [Threshold limit value|TLV], TWA or STEL) determined by the ACGIH professional association. Some, but by no means all, toxic gases are detectable by odor, which can serve as a warning. Among the best known toxic gases are carbon monoxide, chlorine, nitrogen dioxide and phosgene.

List of methanol poisoning incidents

Outbreaks of methanol poisoning have occurred when methanol is used to adulterate moonshine (bootleg liquor).Methanol has a high toxicity in humans. If as little as 10 ml of pure methanol is ingested, for example, it can break down into formic acid, which can cause permanent blindness by destruction of the optic nerve, and 30 ml is potentially fatal, although the median lethal dose is typically 100 ml (3.4 fl oz) (i.e. 1–2 ml/kg body weight of pure methanol). This does not happen with ethanol, which breaks down into acetic acid, which is non-toxic on small amounts. Reference dose for methanol is 0.5 mg/kg/day. Toxic effects take hours to start, and effective antidotes can often prevent permanent damage. Because of its similarities in both appearance and odor to ethanol (the alcohol in beverages), it is difficult to differentiate between the two.

Median toxic dose

In toxicology, the median toxic dose (TD50) of a drug or toxin is the dose at which toxicity occurs in 50% of cases. The type of toxicity should be specified for this value to have meaning for practical purposes. The median toxic dose encompasses the category of toxicity that is greater than half maximum effective concentration (ED50) but less than the median lethal dose (LD50). However, for some highly potent toxins (ex. lofentanil, botulinum toxin) the difference between the ED50 and TD50 is so minute that the values assigned to them may be approximated to equal doses. Since toxicity need not be lethal, the TD50 is generally lower than the median lethal dose (LD50), and the latter can be considered an upper bound for the former. However, since the toxicity is above the effective limit, the TD50 is generally greater than the ED50. If the result of a study is a toxic effect that does not result in death, it is classified as this form of toxicity. Toxic effects can be defined differently, sometimes considering the therapeutic effect of a substance to be toxic (such as with chemotherapeutics) which can lead to confusion and contention regarding a substance's TD50. Examples of these toxic endpoints include cancer, blindness, anemia, birth defects, etc.

Nuciferine

Nuciferine is an alkaloid found within the plants Nymphaea caerulea and Nelumbo nucifera. It has a profile of action associated with dopamine receptor blockade. It induces sedation, hypothermia, ptosis, and (in higher doses) catalepsy; it inhibits spontaneous motor activity, conditioned avoidance response, amphetamine toxicity and stereotypy. Nuciferine may also potentiate morphine analgesia. The median lethal dose in mice is 289 mg/kg. It is structurally related to apomorphine.

PMSF

In biochemistry, phenylmethylsulfonyl fluoride (PMSF) is a serine protease inhibitor (serine hydrolase inactivator) commonly used in the preparation of cell lysates. PMSF does not inactivate all serine proteases. The effective concentration of PMSF is between 0.1 - 1 mM. The half-life is short in aqueous solutions (110 min at pH 7, 55 min at pH 7.5, and 35 min at pH 8, all at 25 °C). Stock solutions are usually made up in anhydrous ethanol, isopropanol, or corn oil and diluted immediately before use.

PMSF binds specifically to the active site serine residue in serine hydrolases. It does not bind to any other serine residues in the protein. This is a result of the hyperactivity of that serine residue caused by the specific environmental conditions in the enzyme's active site (catalytic triad). Because PMSF binds covalently to the enzyme, the complex can be viewed by X-ray crystallography; it can therefore be used as a chemical label to identify an essential active site serine in an enzyme.

Enzyme(active)Ser-O-H + F-SO2CH2C6H5 → EnzymeSer-O-SO2CH2C6H5 + HFSerine protease + PMSF → Irreversible enzyme-PMS complex + HFThe median lethal dose is less than 500 mg/kg (acetylcholine esterase inactivator!). PMSF should be handled only inside a fume hood and while wearing gloves. DMSO is sometimes recommended as solvent for stock solutions, but should not be used as it makes intact skin permeable for PMSF.

Paraformaldehyde

Paraformaldehyde (PFA) is the smallest polyoxymethylene, the polymerization product of formaldehyde with a typical degree of polymerization of 8–100 units. Paraformaldehyde commonly has a slight odor of formaldehyde due to decomposition. Paraformaldehyde is a poly-acetal.

Phosalone

Phosalone is an organophosphate chemical commonly used as an insecticide and acaricide. It is developed by Rhône-Poulenc in France but EU eliminated it from pesticide registration on December 2006.

The median lethal dose of oral exposure in rat is 85 mg/kg and that of dermal is 390 mg/kg.。It is a weak acetylcholinesterase inhibitor. It is taken by not only oral and inhalation but skin and it causes toxic symptoms peculiar to organophosphorus compounds such as miosis, hypersalivation, hyperhidrosis, chest pressure, pulmonary edema and fecal incontinence. It is flammable and decomposes to toxic gases such as phosphorus oxides, sulfur oxides and nitrogen oxides. It is harmful especially to water creatures.

Reed–Muench method

See article above for overview of 50% endpoints and comparison with other methods of calculating 50% endpoints.

The Reed–Muench method is a simple method for determining 50% endpoints in experimental biology, that is, the concentration of a test substance that produces an effect of interest in half of the test units. Examples include LD50 (the median lethal dose of a toxin or pathogen), EC50 and IC50 (half maximal effective or inhibitory concentration, respectively, of a drug), and TCID50 (50% tissue culture infectious dose of a virus).

The reason for using 50% endpoints is that many dose-response relationships in biology follow a logistic function that flattens out as it approaches the minimal and maximal responses, so it is easier to measure the concentration of the test substance that produces a 50% response.

Reverse pharmacology

In the field of drug discovery, reverse pharmacology also known as target-based drug discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target will have beneficial therapeutic effects. Screening of chemical libraries of small molecules is then used to identify compounds that bind with high affinity to the target. The hits from these screens are then used as starting points for drug discovery. This method became popular after the sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins. This method is the most widely used in drug discovery today. Differently than the classical (forward) pharmacology, with the reverse pharmacology approach in vivo efficacy of identified active (lead) compounds is usually performed in the final drug discovery stages.

Ricin

Ricin ( RY-sin), 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 (LD50) 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.

Tabasco sauce

Tabasco sauce is a brand of hot sauce made exclusively from tabasco peppers (Capsicum frutescens var. tabasco), vinegar, and salt. It is produced by McIlhenny Company of Avery Island, Louisiana.

Taipoxin

Taipoxin is a potent myo- and neurotoxin, which was isolated from the venom of the coastal taipan Oxyuranus scutellatus or also known as the common taipan. Taipoxin like many other pre-synaptic neurotoxins are phospholipase A2 (PLA2) toxins, which inhibit/complete block the release of the motor transmitter acetylcholine and lead to death by paralysis of the respiratory muscles (asphyxia). It is the most lethal neurotoxin isolated from any snake venom to date.

The molecular mass of the heterotrimer is about 46,000 Dalton; comprising 1:1:1 α, β and γ monomers. Median lethal dose (LD50) for mice is around 1–2 μg/kg (subcutaneous injection).

Thallium(I) carbonate

Thallium(I) carbonate (Tl2CO3) is a chemical compound. It can be used for the manufacture of imitation diamonds, in chemical analysis to test for carbon disulfide, and as a fungicide. Like other thallium compounds, it is considered extremely toxic, with an oral median lethal dose of 21 mg/kg in mice. Due to its toxicity, it is listed in the United States List of Extremely Hazardous Substances as of 2007.

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