Median lethal dose

Last updated

In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a given substance. [1] 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 higher toxicity.

Contents

The term LD50 is generally attributed to John William Trevan. [2] The test was created by J. W. Trevan in 1927. [3] 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. [4] [5]

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. [6]

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, for ionizing radiation, 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. 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 LD50s 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. [7]

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. [8]

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

SubstanceAnimal, routeLD50
{LC50}
LD50 : g/kg
{LC50 : g/L}
standardised		Reference
Water (H2O)rat, oral>>90 [9]
Sucrose (table sugar)rat, oral29.7 [10]
Corn Syrup rat, oral25.8 [11]
Glucose (blood sugar)rat, oral25.8 [12]
Monosodium glutamate (MSG)rat, oral16.6 [13]
Stevioside (from stevia)mice and rats, oral15 [14]
Gasoline (petrol)rat14.0 [15]
Vitamin C (ascorbic acid)rat, oral11.9 [16]
Glyphosate (isopropylamine salt of)rat, oral10.537 [17]
Lactose (milk sugar)rat, oral10 [18]
Aspartame mice, oral10 [19]
Urea (OC(NH2)2)rat, oral8.471 [20]
Cyanuric acid rat, oral7.7 [21]
Cadmium sulfide (CdS)rat, oral7.08 [22]
Ethanol (CH3CH2OH)rat, oral7.06 [23]
Sodium isopropyl methylphosphonic acid (IMPA, metabolite of sarin)rat, oral6.86 [24]
Melamine rat, oral6 [21]
Taurine rat, oral5 [25]
Melamine cyanurate rat, oral4.1 [21]
Fructose (fruit sugar)rat, oral4,000 mg/kg4 [26]
Sodium molybdate (Na2MoO4)rat, oral4,000 mg/kg4 [27]
Sodium chloride (table salt)rat, oral3,000 mg/kg3 [28]
Aspirin (acetylsalicylic acid)rat, oral1,944 mg/kg1.944 [29]
Delta-9-tetrahydrocannabinol (THC)rat, oral1,270 mg/kg1.27 [30]
Cannabidiol (CBD)rat, oral980 mg/kg0.98 [31]
Methanol (CH3OH)human, oral0.81 [32]
Trinitrotoluene (TNT)rat, oral790 mg/kg0.790
Arsenic (As)rat, oral763 mg/kg0.763 [33]
Ibuprofen rat, oral636 mg/kg0.636 [34]
Formaldehyde (CH2O)rat, oral600–800 mg/kg0.6 [35]
Solanine (main alkaloid in the several plants in Solanaceae amongst them Solanum tuberosum )rat, oral (2.8 mg/kg human, oral)0.590 [36]
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}		 [37]
Coumarin (benzopyrone, from Cinnamomum aromaticum and other plants)rat, oral293 mg/kg0.293 [38]
Psilocybin (from magic mushrooms)mouse, oral280 mg/kg0.280 [39]
Hydrochloric acid (HCl)rat, oral238–277 mg/kg0.238 [40]
Ketamine rat, intraperitoneal229 mg/kg0.229 [41]
Paracetamol (acetaminophen)rat, oral200 mg/kg0.2 [42]
Caffeine rat, oral192 mg/kg0.192 [43]
Arsenic trisulfide (As2S3)rat, oral185–6,400 mg/kg0.185–6.4 [44]
Sodium nitrite (NaNO2)rat, oral180 mg/kg0.18 [45]
Methylenedioxymethamphetamine (MDMA, ecstasy)rat, oral160 mg/kg0.18 [46]
Uranyl acetate dihydrate (UO2(CH3COO)2)mouse, oral136 mg/kg0.136 [47]
Dichlorodiphenyltrichloroethane (DDT)mouse, oral135 mg/kg0.135 [48]
Uranium (U)mice, oral0.114 [47]
Bisoprolol mouse, oral100 mg/kg0.1 [49]
Cocaine mouse, oral96 mg/kg0.096 [50]
Cobalt(II) chloride (CoCl2)rat, oral80 mg/kg0.08 [51]
Cadmium oxide (CdO)rat, oral72 mg/kg0.072 [52]
Thiopental sodium (used in lethal injection)rat, oral64 mg/kg0.064 [53]
Demeton-S-methyl rat, oral60 mg/kg0.060 [54]
Methamphetamine rat, intraperitoneal57 mg/kg0.057 [55]
Sodium fluoride (NaF)rat, oral52 mg/kg0.052 [56]
Nicotine mouse and rat, oral

human, smoking

50 mg/kg0.05 [57]
Pentaborane human, oral50 mg/kg0.05 [58]
Capsaicin mouse, oral47.2 mg/kg0.0472 [59]
Vitamin D3 (cholecalciferol)rat, oral37 mg/kg0.037 [60]
Piperidine (from black pepper)rat, oral30 mg/kg0.030 [61]
Heroin (diamorphine)mouse, intravenous21.8 mg/kg0.0218 [62]
Lysergic acid diethylamide (LSD)rat, intravenous16.5 mg/kg0.0165 [63]
Arsenic trioxide (As2O3)rat, oral14 mg/kg0.014 [64]
Metallic arsenic (As)rat, intraperitoneal 13 mg/kg0.013 [65]
Sodium cyanide (NaCN)rat, oral6.4 mg/kg0.0064 [66]
Chlorotoxin (CTX, from scorpions)mice4.3 mg/kg0.0043 [67]
Hydrogen cyanide (HCN)mouse, oral3.7 mg/kg0.0037 [68]
Carfentanil rat, intravenous3.39 mg/kg0.00339 [69]
Nicotine (from various Solanaceae genera)mice, oral3.3 mg/kg0.0033 [57]
White phosphorus (P)rat, oral3.03 mg/kg0.00303 [70]
Strychnine (from Strychnos nux-vomica )human, oral1–2 mg/kg (estimated)0.001–0.002 [71]
Aconitine (from Aconitum napellus and related species)human, oral0.001–0.002 [72]
Mercury(II) chloride (HgCl2)rat, oral1 mg/kg0.001 [73]
Cantharidin (from blister beetles)human, oral500 μg/kg0.0005 [74]
Aflatoxin B1 (from Aspergillus flavus mold)rat, oral480 μg/kg0.00048 [75]
Plutonium (Pu)dog, intravenous320 μg/kg0.00032 [76]
Bufotoxin (from Bufo toads)cat, intravenous0.0003 [77]
Brodifacoum rat, oral270 μg/kg0.00027 [78]
Caesium-137 (137
Cs)		mouse, parenteral0.000245 [79]
Sodium fluoroacetate (CH2FCOONa)rat, oral220 μg/kg0.00022 [80]
Chlorine trifluoride (ClF3)mouse, absorption through skin178 μg/kg0.000178 [81]
Sarin mouse, subcutaneous injection0.000172 [82]
Robustoxin (from Sydney funnel-web spider)mice0.000150 [83]
VX human, oral, inhalation, absorption through skin/eyes0.00014 [84]
Venom of the Brazilian wandering spider rat, subcutaneous0.000134 [85]
Amatoxin (from Amanita phalloides mushrooms)human, oral100 μg/kg0.0001 [86] [87]
Dimethylmercury (Hg(CH3)2)human, transdermal0.000050 [88]
TBPO (t-Butyl-bicyclophosphate)mouse, intravenous36 μg/kg0.000036 [89]
Fentanyl monkey30 μg/kg0.00003 [90]
Venom of the Inland Taipan (Australian snake)rat, subcutaneous0.000025 [91]
Ricin (from castor oil plant)rat, intraperitoneal
rat, oral		0.000022
0.02		 [92]
2,3,7,8-Tetrachlorodibenzodioxin (TCDD, in Agent Orange)rat, oral0.00002
Tetrodotoxin from the blue-ringed octopus intravenous0.0000082 [93]
CrTX-A (from Carybdea rastonii box jellyfish venom)crayfish, intraperitoneal0.000005 [94]
Latrotoxin (from widow spider venom)mice0.0000043 [95] [ self-published source? ]
Epibatidine (from Epipedobates anthonyi poison dart frog)mouse, intravenous1.46-13.98 μg/kg0.00000146 [96]
Batrachotoxin (from poison dart frog)human, sub-cutaneous injection0.000002 [97]
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

[ citation needed ]
Saxitoxin (from certain marine dinoflagellates)human, intravenously

human, oral

0.6 μg/kg

5.7 μg/kg

0.0000006

0.0000057

 [97]
Pacific Ciguatoxin-1 (from ciguateric fish)mice, intraperitoneal250 ng0.00000025 [98]
Palytoxin (from Palythoa coral)mouse, intravenous45 ng/kg

2.3–31.5 μg/kg

0.000000045

0.0000023

 [99]
Maitotoxin (from ciguateric fish)mouse, intraperitoneal 50 ng0.00000005 [100]
Polonium-210 (210
Po)		human, inhalation0.00000001 [101]
Diphtheria toxin (from Corynebacterium )mice0.00000001 [102]
Shiga toxin (from Shigella bacteria)mice0.000000002 [102]
Tetanospasmin (from Clostridium tetani )mice0.000000002 [102]
Botulinum toxin (from Clostridium botulinum )human, oral, injection, inhalation0.000000001 [103]
Ionizing radiation human, irradiation3–5  Gy (Gray)— [104] [105] [106]

Poison scale

Negative values of the decimal logarithm of the median lethal dose LD50 (-log10(LD50)) on a linearized toxicity scale encompassing 11 orders of magnitude. Water occupies the lowest toxicity position (1) while the toxicity scale is dominated by the botulinum toxin (12). Poison-Scale-long.jpg
Negative values of the decimal logarithm of the median lethal dose LD50 (−log10(LD50)) on a linearized toxicity scale encompassing 11 orders of magnitude. Water occupies the lowest toxicity position (1) while the toxicity scale is dominated by the botulinum toxin (12).

The LD50 values have a very wide range. The botulinum toxin as the most toxic substance known has an LD50 value of 1 ng/kg, while the most non-toxic substance water has an LD50 value of more than 90 g/kg; a difference of about 1 in 100 billion, or 11 orders of magnitude. As with all measured values that differ by many orders of magnitude, a logarithmic view is advisable. Well-known examples are the indication of the earthquake strength using the Richter scale, the pH value, as a measure for the acidic or basic character of an aqueous solution or of loudness in decibels. In this case, the negative decimal logarithm of the LD50 values, which is standardized in kg per kg body weight, is considered −log10(LD50).

The dimensionless value found can be entered in a toxin scale. Water as the baseline substance is neatly 1 in the negative logarithmic toxin scale.

Animal rights concerns

Animal-rights and animal-welfare groups, such as Animal Rights International, [108] 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).

Procedures

A number of procedures have been defined to derive the LD50. The earliest was the 1927 "conventional" procedure by Trevan, which requires 40 or more animals. The fixed-dose procedure, proposed in 1984, estimates a level of toxicity by feeding at defined doses and looking for signs of toxicity (without requiring death). [109] The up-and-down procedure, proposed in 1985, yields an LD50 value while dosing only one animal at a time. [110] [111]

See also

Other measures of toxicity

Related Research Articles

<span class="mw-page-title-main">Toxicology</span> Study of substances harmful to living organisms

Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure, route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia.

<span class="mw-page-title-main">Soman</span> Chemical compound (nerve agent)

Soman is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiting the enzyme cholinesterase. It is an inhibitor of both acetylcholinesterase and butyrylcholinesterase. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations according to UN Resolution 687. Its production is strictly controlled, and stockpiling is outlawed by the Chemical Weapons Convention of 1993 where it is classified as a Schedule 1 substance. Soman was the third of the so-called G-series nerve agents to be discovered along with GA (tabun), GB (sarin), and GF (cyclosarin).

<span class="mw-page-title-main">Toxicity</span> Dose dependant harmfulness of substances

Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ such as the liver (hepatotoxicity). Sometimes the word is more or less synonymous with poisoning in everyday usage.

<span class="mw-page-title-main">Propylene glycol</span> Chemical compound

Propylene glycol (IUPAC name: propane-1,2-diol) is a viscous, colorless liquid. It is almost odorless and has a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH. As it contains two alcohol groups, it is classed as a diol. An aliphatic diol may also be called a glycol. It is miscible with a broad range of solvents, including water, acetone, and chloroform. In general, glycols are non-irritating and have very low volatility.

The therapeutic index is a quantitative measurement of the relative safety of a drug with regard to risk of overdose. It is a comparison of the amount of a therapeutic agent that causes toxicity to the amount that causes the therapeutic effect. The related terms therapeutic window or safety window refer to a range of doses optimized between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.

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 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.

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. To be described as acute toxicity, the adverse effects should occur within 14 days of the administration of the substance.

<span class="mw-page-title-main">Palytoxin</span> Chemical compound

Palytoxin, PTX or PLTX is an intense vasoconstrictor, and is considered to be one of the most poisonous non-protein substances known, second only to maitotoxin in terms of toxicity in mice.

<span class="mw-page-title-main">Theobromine poisoning</span> Overdose reaction to the xanthine alkaloid theobromine

Theobromine poisoning, also informally called chocolate poisoning or cocoa poisoning, is an overdosage reaction to the xanthine alkaloid theobromine, found in chocolate, tea, cola beverages, and some other foods.

In toxicology, the lowest published toxic dose is the lowest dosage per unit of bodyweight of a substance known to have produced signs of toxicity in a particular animal species. When quoting a TDLo, the particular species and method of administration are typically stated.

<span class="mw-page-title-main">Venomous snake</span> Species of the suborder Serpentes that produce venom

Venomous snakes are species of the suborder Serpentes that are capable of producing venom, which they use for killing prey, for defense, and to assist with digestion of their prey. The venom is typically delivered by injection using hollow or grooved fangs, although some venomous snakes lack well-developed fangs. Common venomous snakes include the families Elapidae, Viperidae, Atractaspididae, and some of the Colubridae. The toxicity of venom is mainly indicated by murine LD50, while multiple factors are considered to judge the potential danger to humans. Other important factors for risk assessment include the likelihood that a snake will bite, the quantity of venom delivered with the bite, the efficiency of the delivery mechanism, and the location of a bite on the body of the victim. Snake venom may have both neurotoxic and hemotoxic properties. There are about 600 venomous snake species in the world.

<span class="mw-page-title-main">Globally Harmonized System of Classification and Labelling of Chemicals</span> International standard managed by the United Nations

The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is an internationally agreed-upon standard managed by the United Nations that was set up to replace the assortment of hazardous material classification and labelling schemes previously used around the world. Core elements of the GHS include standardized hazard testing criteria, universal warning pictograms, and safety data sheets which provide users of dangerous goods relevant information with consistent organization. The system acts as a complement to the UN numbered system of regulated hazardous material transport. Implementation is managed through the UN Secretariat. Although adoption has taken time, as of 2017, the system has been enacted to significant extents in most major countries of the world. This includes the European Union, which has implemented the United Nations' GHS into EU law as the CLP Regulation, and United States Occupational Safety and Health Administration standards.

<span class="mw-page-title-main">Brodifacoum</span> Chemical compound

Brodifacoum is a highly lethal 4-hydroxycoumarin vitamin K antagonist anticoagulant poison. In recent years, it has become one of the world's most widely used pesticides. It is typically used as a rodenticide, but is also used to control larger pests such as possums.

The fixed-dose procedure (FDP), proposed in 1992 by the British Toxicology Society, is a method to assess a substance's acute oral toxicity.

<span class="mw-page-title-main">Toxicology testing</span> Biochemical process

Toxicology testing, also known as safety assessment, or toxicity testing, is the process of determining the degree to which a substance of interest negatively impacts the normal biological functions of an organism, given a certain exposure duration, route of exposure, and substance concentration.

<span class="mw-page-title-main">Tutin (toxin)</span> Chemical compound

Tutin is a poisonous plant derivative found in New Zealand tutu plants. It acts as a potent antagonist of the glycine receptor, and has powerful convulsant effects. It is used in scientific research into the glycine receptor. It is sometimes associated with outbreaks of toxic honey poisoning when bees feed on honeydew exudate from the sap-sucking passion vine hopper insect, when the vine hoppers have been feeding on the sap of tutu bushes. Toxic honey is a rare event and is more likely to occur when comb honey is eaten directly from a hive that has been harvesting honeydew from passionvine hoppers feeding on tutu plants.

<span class="mw-page-title-main">Bioassay</span> Analytical method to determine potency and effect of a substance

A bioassay is an analytical method to determine the potency or effect of a substance by its effect on living animals or plants, or on living cells or tissues. A bioassay can be either quantal or quantitative, direct or indirect. If the measured response is binary, the assay is quantal; if not, it is quantitative.

<span class="mw-page-title-main">Cinnamyl acetate</span> Chemical compound

Cinnamyl acetate is a chemical compound of the cinnamyl ester family, in which the variable R group is substituted by a methyl group. As a result of the non-aromatic carbon-carbon double bond, cinnamyl acetate can exist in a Z and an E configuration:

Threshold dose is the minimum dose of drug that triggers minimal detectable biological effect in an animal. At extremely low doses, biological responses are absent for some of the drugs. The increase in dose above threshold dose induces an increase in the percentage of biological responses. Several benchmarks have been established to describe the effects of a particular dose of drug in a particular species, such as NOEL(no-observed-effect-level), NOAEL(no-observed-adverse-effect-level) and LOAEL(lowest-observed-adverse-effect-level). They are established by reviewing the available studies and animal studies. The application of threshold dose in risk assessment safeguards the participants in human clinical trials and evaluates the risks of chronic exposure to certain substances. However, the nature of animal studies also limits the applicability of experimental results in the human population and its significance in evaluating potential risk of certain substances. In toxicology, there are some other safety factors including LD50, LC50 and EC50.

References

  1. ↑ "Absolute lethal dose (LD100)". IUPAC Gold Book. International Union of Pure and Applied Chemistry. Archived from the original on 2019-07-01. Retrieved 2019-07-01.
  2. ↑ "John William Trevan, 1887-1956". Biographical Memoirs of Fellows of the Royal Society. 3: 273–288. 1957. doi:10.1098/rsbm.1957.0019. ISSN   0080-4606. Archived from the original on 2020-03-28. Retrieved 2024-03-31.
  3. ↑ "What is a LD50 and LC50?". OSH Answers Fact Sheets. Canadian Centre for Occupational Health and Safety. 5 October 2021. Archived from the original on 26 June 2015. Retrieved 15 July 2006.
  4. ↑ "Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX and BOTOX Cosmetic (onabotulinumtoxinA)". Allergan Web site. 24 June 2011. Archived from the original on 26 June 2011. Retrieved 2012-08-15.
  5. ↑ Gaul GM (12 April 2008). "In U.S., Few Alternatives To Testing On Animals". Washington Post . Archived from the original on 2012-11-12. Retrieved 2011-06-26.
  6. ↑ Doris V. Sweet, ed. (July 1997). "Registry of Toxic Effects of Chemical Substances (RTECS) / Comprehensive Guide to the RTECS" (PDF). U.S. Department of Health and Human Services. DHHS (NIOSH) Publication No. 97-119. Archived from the original (PDF) on 2013-05-16.
  7. ↑ Ernest Hodgson (2004). A Textbook of Modern Toxicology. Wiley-Interscience (3rd ed.).[ page needed ]
  8. ↑ "Therapeutic index | CME at Pharmacology Corner". pharmacologycorner.com. 2011-01-26. Retrieved 2024-07-15.
  9. ↑ "Material Safety Data Sheet Water MSDS". Section 11: Toxicological Information for the LD50 verification. Archived from the original on 2012-09-02. Retrieved 2012-05-09.
  10. ↑ "Safety (MSDS) data for sucrose". ox.ac.uk. Archived from the original on 2011-06-12.
  11. ↑ "Safety (MSDS) data for Corn Syrup". fishersci.com. Archived from the original on 2022-09-21. Retrieved 2022-09-21.
  12. ↑ "Safety (MSDS) data for glucose" (PDF). utoronto.ca. Archived from the original (PDF) on 2017-01-01. Retrieved 2016-12-31.
  13. ↑ Walker R, Lupien JR (April 2000). "The safety evaluation of monosodium glutamate". The Journal of Nutrition. 130 (4S Suppl): 1049S–1052S. doi: 10.1093/jn/130.4.1049S . PMID   10736380.
  14. ↑ Toskulkao C, Chaturat L, Temcharoen P, Glinsukon T (1997). "Acute toxicity of stevioside, a natural sweetener, and its metabolite, steviol, in several animal species". Drug and Chemical Toxicology. 20 (1–2): 31–44. doi:10.3109/01480549709011077. PMID   9183561.
  15. ↑ "Toxicological profile for gasoline" (PDF). U.S. Department of Health and Human Services, Public Health Service Agency for Toxic Substances and Disease Registry. June 1995. p. 47. Archived from the original (PDF) on 2017-05-15. Retrieved 2020-01-05.
  16. ↑ "Safety (MSDS) data for ascorbic acid". Oxford University. 2005-10-09. Archived from the original on 2007-02-09. Retrieved 2007-02-21.
  17. ↑ "Glyphosate-isopropylammonium". PubChem. Archived from the original on 2021-03-02. Retrieved 2019-01-17.
  18. ↑ "Safety (MSDS) data for Lactose" (PDF). Archived from the original (PDF) on 2016-08-03. Retrieved 2016-12-31.
  19. ↑ "Material Safety Data Sheet: Aspartame" (PDF). Spectrum. Archived from the original (PDF) on 2016-12-26.
  20. ↑ "Safety (MSDS) data for urea". 2015-03-06. Section 11: Toxicological Information for the LD50 verification. Archived from the original on 2015-03-01. Retrieved 2015-03-06.
  21. 1 2 3 A.A. Babayan, A.V.Aleksandryan, "Toxicological characteristics of melamine cyanurate, melamine and cyanuric acid", Zhurnal Eksperimental'noi i Klinicheskoi Meditsiny, Vol.25, 345–9 (1985). Original article in Russian.
  22. ↑ Advanced Search – Alfa Aesar – A Johnson Matthey Company Archived 2015-07-24 at the Wayback Machine . Alfa.com. Retrieved on 2013-07-17.
  23. ↑ "Safety (MSDS) data for ethyl alcohol". ox.ac.uk. Archived from the original on 2011-07-14.
  24. ↑ Mecler FJ (May 1981). Mammalian Toxological Evaluation of DIMP and DCBP (Phase 3 – IMPA) (Final report). Litton Bionetics, Inc. Archived from the original on October 4, 2013. The oral LD50 values for the test material, IMPA, were 7650 and 6070 mg/kg for male and female rats, respectively.
  25. ↑ "Safety data for taurine" (PDF). scbt.com. Archived from the original (PDF) on 2017-01-18. Retrieved 2017-01-18.
  26. ↑ "Safety (MSDS) data for fructose". sciencelab.com. Archived from the original on 2017-07-02. Retrieved 2016-12-31.
  27. ↑ "Safety (MSDS) data for sodium molybdate". ox.ac.uk. Archived from the original on 2011-01-28.
  28. ↑ "Safety (MSDS) data for sodium chloride". ox.ac.uk. Archived from the original on 2011-06-07.
  29. ↑ "Safety (MSDS) data for paracetamol". Millipore Sigma. Merck KGaA. Archived from the original on 2021-03-02. Retrieved 2020-01-06.
  30. ↑ Rosenkrantz H, Heyman IA, Braude MC (April 1974). "Inhalation, parenteral and oral LD50 values of delta 9-tetrahydrocannabinol in Fischer rats". Toxicology and Applied Pharmacology. 28 (1): 18–27. doi:10.1016/0041-008X(74)90126-4. PMID   4852457.
  31. ↑ "MSDS of CBD" (PDF). chemblink.com. Archived from the original (PDF) on 2016-12-26. Retrieved 2016-12-26.
  32. ↑ "Methanol Poisoning Overview". antizol.com. Archived from the original on 2011-10-05.
  33. ↑ "Arsenic". PubChem. Archived from the original on 2021-05-12. Retrieved 2020-01-06.
  34. ↑ "Ibuprofen – National Library of Medicine HSDB Database". toxnet.nlm.nih.gov. Archived from the original on 2018-08-04. Retrieved 2016-12-26.
  35. ↑ "Formaldehyde SIDS Initial Assessment Report" (PDF). inchem.org. Archived from the original (PDF) on 2018-06-13. Retrieved 2016-12-26.
  36. ↑ "Solanine – National Library of Medicine HSDB Database". toxnet.nlm.nih.gov. Archived from the original on 2021-01-19. Retrieved 2019-01-17.
  37. ↑ Frank T. Sanders, ed. (August 2006). Reregistration Eligibility Decision for Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) (PDF) (Report). U.S. Environmental Protection Agency Office of Prevention, Pesticides, and Toxic Substances. p. 114. Archived from the original (PDF) on 2009-10-24. Retrieved 2009-03-31.
  38. ↑ Coumarin Material Safety Data Sheet (MSDS) Archived 2004-10-21 at the Wayback Machine
  39. ↑ Rumack BH, Spoerke DJ (27 September 1994). Handbook of Mushroom Poisoning: Diagnosis and Treatment. CRC Press. ISBN   978-0-8493-0194-0 – via Google Books.
  40. ↑ "Material Safety Data Sheet: Hydrochloric acid 32-38% solution". Fisher. 1 April 2008. Archived from the original on 6 May 2021. Retrieved 24 December 2020.
  41. ↑ "Ketamine" (PDF). nih.gov. Archived (PDF) from the original on 2021-03-20. Retrieved 2016-12-26.
  42. ↑ "Safety (MSDS) data for acetylsalicylic acid". ox.ac.uk. Archived from the original on 2011-07-16.
  43. ↑ Boyd EM (May 1959). "The acute oral toxicity of caffeine". Toxicology and Applied Pharmacology. 1 (3): 250–257. doi:10.1016/0041-008X(59)90109-7. PMID   13659532.
  44. ↑ "Material Safety Data Sheet – Spent Metal Catalyst" (PDF). Archived from the original (PDF) on 2011-09-28.
  45. ↑ "Safety (MSDS) data for sodium nitrite". ox.ac.uk.[ dead link ]
  46. ↑ Gable RS (September 2004). "Acute toxic effects of club drugs". Journal of Psychoactive Drugs. 36 (3): 303–313. doi:10.1080/02791072.2004.10400031. PMID   15559678. S2CID   30689421.
  47. 1 2 "Chemical toxicity of uranium" (PDF). who.int. Archived (PDF) from the original on 2021-03-09. Retrieved 2020-10-05.
  48. ↑ Hayes WJ, Simmons SW, Knipling EF (1959). "Dose-Mortality Relationships in Animals". DDT: The Insecticide Dichlorodiphenyltrichloroethane and Its Significance / Das Insektizid Dichlordiphenyltrichloräthan und Seine Bedeutung. pp. 18–40. doi:10.1007/978-3-0348-6809-9_3. ISBN   978-3-0348-6796-2.
  49. ↑ "Bisoprolol". www.drugbank.ca. Archived from the original on 2020-06-17. Retrieved 2012-06-13.
  50. ↑ "Cocaine". www.drugbank.ca. Archived from the original on 2016-11-20. Retrieved 2016-12-26.
  51. ↑ "Safety (MSDS) data for cobalt (II) chloride". ox.ac.uk. Archived from the original on 2011-04-07.
  52. ↑ Safety (MSDS) data for cadmium oxide [ permanent dead link ]
  53. ↑ "Thiopental sodium". Pubchem. Archived from the original on 2021-01-26. Retrieved 2017-01-06.
  54. ↑ "Demeton-s-methyl". Extoxnet. September 1995. Archived from the original on 2019-06-04. Retrieved 2019-07-21.
  55. ↑ Kiyatkin EA, Sharma HS (2009). "Acute Methamphetamine Intoxication". New Concepts of Psychostimulant Induced Neurotoxicity. International Review of Neurobiology. Vol. 88. pp. 65–100. doi:10.1016/S0074-7742(09)88004-5. ISBN   978-0-12-374504-0. PMC   3145326 . PMID   19897075.
  56. ↑ "Sodium fluoride". hazard.com. Archived from the original on 2011-09-28. Retrieved 2011-07-31.{{cite web}}: CS1 maint: unfit URL (link)
  57. 1 2 Mayer B (January 2014). "How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century". Archives of Toxicology. 88 (1): 5–7. doi:10.1007/s00204-013-1127-0. PMC   3880486 . PMID   24091634.
  58. ↑ "Pentaborane chemical and safety data" (PDF). noaa.gov. Archived (PDF) from the original on 2013-05-23. Retrieved 2011-09-30.
  59. ↑ "Capsaicin Material Safety Data Sheet". sciencelab.com. 2007. Archived from the original (PDF) on 2007-09-29. Retrieved 2007-07-13.
  60. ↑ "MSDS for cholecalciferol crystalline" (PDF). hmdb.ca. Archived from the original (PDF) on 2016-12-26. Retrieved 2016-12-26.
  61. ↑ "Material Safety Data Sheet: Piperidine". Fisher. 29 October 2007. Archived from the original on 4 March 2016. Retrieved 24 December 2020.
  62. ↑ "Diamorphine (PIM 261F, French)". www.inchem.org. Archived from the original on 2016-05-02. Retrieved 2016-12-26.
  63. ↑ Erowid LSD (Acid) Vault : Fatalities / Deaths Archived 2021-06-30 at the Wayback Machine . Erowid.org. Retrieved on 2013-07-17.
  64. ↑ "Safety (MSDS) data for arsenic trioxide". ox.ac.uk. Archived from the original on 2010-03-09.
  65. ↑ "Safety (MSDS) data for metallic arsenic". ox.ac.uk. Archived from the original on 2011-01-14.
  66. ↑ "Safety (MSDS) data for sodium cyanide". ox.ac.uk. Archived from the original on 2009-01-13.
  67. ↑ "Chlorotoxin: A Helpful Natural Scorpion Peptide to Diagnose Glioma and Fight Tumor Invasion". Archived from the original on 2016-12-28. Retrieved 2016-12-27.
  68. ↑ "Safety (MSDS) data for hydrogen cyanide" (PDF). orica.com. Archived from the original (PDF) on 2016-12-26. Retrieved 2016-12-26.
  69. ↑ "Critical Review Carfentanil" (PDF). Archived (PDF) from the original on 2020-11-12. Retrieved 2019-01-31.
  70. ↑ "Hexachloroethane" (PDF). Archived (PDF) from the original on 2006-06-30. Retrieved 2014-01-03.
  71. ↑ INCHEM: Chemical Safety Information from Intergovernmental Organizations: Strychnine Archived 2015-01-03 at the Wayback Machine .
  72. ↑ Gao X, Hu J, Zhang X, Zuo Y, Wang Y, Zhu S (2018-04-09). "Research progress of aconitine toxicity and forensic analysis of aconitine poisoning". Forensic Sciences Research. 5 (1): 25–31. doi:10.1080/20961790.2018.1452346. PMC   7241456 . PMID   32490307.
  73. ↑ "Mercuric Chloride Safety Data Sheet" (PDF). LabChem. p. 6. Archived from the original (PDF) on 2019-11-26. Retrieved 2020-01-06.
  74. ↑ Meister RT, Sine C (2013). Crop Protection Handbook. Vol. 99. Willoughby, Ohio: Meister Pub Co. p. 664. ISBN   978-1892829269.
  75. ↑ "Safety (MSDS) data for aflatoxin B1". ox.ac.uk. Archived from the original on 2010-08-11.
  76. ↑ Voelz GL, Buican IG (2000). "Plutonium and Health — How great is the risk?" (PDF). Los Alamos Science (26): 74–89. Archived (PDF) from the original on 2021-01-18. Retrieved 2016-12-26.
  77. ↑ "Bufotoxin". ChemIDplus. U.S. National Library of Medicine. Archived from the original on 2021-01-19. Retrieved 2016-12-27.
  78. ↑ "Brodifacoum (PDS)". Inchem.org. Archived from the original on 2013-12-13. Retrieved 2017-12-05.
  79. ↑ Moskalev YI (1961). "Biological Effects of Cesium-137". In Lebedinskiĭ AV, Moskalev YI (eds.). Distribution, Biological Effects, and Migration of Radioactive Isotopes. Translation Series. United States Atomic Energy Commission (published April 1974). p. 220. AEC-tr-7512. [(21.5 μCi/g) × (1000 g/kg) × (0.0114 μg/μCi) = 245 μg/kg]
  80. ↑ Meister R, Since C (2013). Crop Protection Handbook 2013. Willoughby, Ohio: Meister Pub Co. p. 664. ISBN   9781892829269.
  81. ↑ "CDC - Immediately Dangerous to Life or Health Concentrations (IDLH): Chlorine trifluoride - NIOSH Publications and Products". www.cdc.gov. 2018-11-02. Archived from the original on 2022-07-11. Retrieved 2022-07-13.
  82. ↑ Inns RH, Tuckwell NJ, Bright JE, Marrs TC (July 1990). "Histochemical demonstration of calcium accumulation in muscle fibres after experimental organophosphate poisoning". Human & Experimental Toxicology. 9 (4): 245–250. doi:10.1177/096032719000900407. PMID   2390321. S2CID   20713579.
  83. ↑ Sheumack DD, Baldo BA, Carroll PR, Hampson F, Howden ME, Skorulis A (1984). "A comparative study of properties and toxic constituents of funnel web spider (Atrax) venoms". Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology. 78 (1): 55–68. doi:10.1016/0742-8413(84)90048-3. PMID   6146485.
  84. ↑ Munro N (January 1994). "Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: implications for public protection". Environmental Health Perspectives. 102 (1): 18–38. doi:10.1289/ehp.9410218. PMC   1567233 . PMID   9719666.
  85. ↑ Venomous Animals and their Venoms, vol. III, ed. Wolfgang Bücherl and Eleanor Buckley
  86. ↑ Hallen HE, Luo H, Scott-Craig JS, Walton JD (November 2007). "Gene family encoding the major toxins of lethal Amanita mushrooms". Proceedings of the National Academy of Sciences of the United States of America. 104 (48): 19097–19101. doi:10.1073/pnas.0707340104. PMC   2141914 . PMID   18025465.
  87. ↑ Madore F, Bouchard J (2019). "Plasmapheresis in Acute Intoxication and Poisoning". Critical Care Nephrology. Elsevier. pp. 595–600.e3. doi:10.1016/b978-0-323-44942-7.00100-x. ISBN   978-0-323-44942-7.
  88. ↑ Blayney MB (February 2001). "The need for empirically derived permeation data for personal protective equipment: the death of Dr. Karen E. Wetterhahn". Applied Occupational and Environmental Hygiene. 16 (2): 233–236. doi:10.1080/104732201460389. PMID   11217716.
  89. ↑ Milbrath DS, Engel JL, Verkade JG, Casida JE (February 1979). "Structure--toxicity relationships of 1-substituted-4-alkyl-2,6,7-trioxabicyclo[2.2.2.]octanes". Toxicology and Applied Pharmacology. 47 (2): 287–293. doi:10.1016/0041-008x(79)90323-5. PMID   452023.
  90. ↑ "Fentanyl". www.drugbank.ca. Archived from the original on 2017-07-11. Retrieved 2017-09-29.
  91. ↑ LD50 for various snakes Archived 2012-02-01 at the Wayback Machine . Seanthomas.net. Retrieved on 2013-07-17.
  92. ↑ "Ricin (from Ricinus communis) as undesirable substances in animal feed - Scientific Opinion of the Panel on Contaminants in the Food Chain". EFSA Journal. 6 (9): 726. 2008. CiteSeerX   10.1.1.333.8413 . doi:10.2903/j.efsa.2008.726.
  93. ↑ Knutsen HK, Alexander J, Barregård L, Bignami M, Brüschweiler B, Ceccatelli S, et al. (April 2017). "Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods". EFSA Journal. European Food Safety Authority. 15 (4): e04752. doi: 10.2903/j.efsa.2017.4752 . PMC   7010203 . PMID   32625458. S2CID   54043321.
  94. ↑ Nagai H (2003). "Recent Progress in Jellyfish Toxin Study". Journal of Health Science. 49 (5): 337–340. doi: 10.1248/jhs.49.337 .
  95. ↑ Henderson N, Wright K, Morgan D, Tantum P. "Black Widow Venom (α-Latrotoxin)". Archived from the original (pptx) on 2016-12-26. Retrieved 2016-12-26.
  96. ↑ Sihver W, Långström B, Nordberg A (2000). "Ligands for in vivo imaging of nicotinic receptor subtypes in Alzheimer brain". Acta Neurologica Scandinavica. Supplementum. 176 (s176): 27–33. doi: 10.1034/j.1600-0404.2000.00304.x . PMID   11261802. S2CID   23541883.
  97. 1 2 Patocka J, Streda L (2002). "Brief review of natural nonprotein neurotoxins". ASA Newsletter. 2 (2): 16–24.
  98. ↑ Caillaud A, de la Iglesia P, Darius HT, Pauillac S, Aligizaki K, Fraga S, et al. (June 2010). "Update on methodologies available for ciguatoxin determination: perspectives to confront the onset of ciguatera fish poisoning in Europe". Marine Drugs. 8 (6): 1838–1907. doi: 10.3390/md8061838 . PMC   2901828 . PMID   20631873.
  99. ↑ Ramos V, Vasconcelos V (June 2010). "Palytoxin and analogs: biological and ecological effects". Marine Drugs. 8 (7): 2021–2037. doi: 10.3390/md8072021 . PMC   2920541 . PMID   20714422.
  100. ↑ "PubChem Compound Summary for CID 71460273, Maitotoxin". PubChem . National Center for Biotechnology Information. Archived from the original on 2020-11-01. Retrieved 2020-12-25.
  101. ↑ Topic 2 Toxic Chemicals and Toxic Effects Archived 2007-09-29 at the Wayback Machine
  102. 1 2 3 Toolson E. "Representative LD50 Values" (PDF). Archived from the original (PDF) on 2015-04-12. Retrieved 2016-12-26.
  103. ↑ Fleming DO, Hunt DL (2000). Biological Safety: principles and practices. Washington, DC: ASM Press. p.  267. ISBN   978-1-55581-180-8.
  104. ↑ Ryan JL (March 2012). "Ionizing radiation: the good, the bad, and the ugly". The Journal of Investigative Dermatology. 132 (3 Pt 2): 985–993. doi:10.1038/jid.2011.411. PMC   3779131 . PMID   22217743.
  105. ↑ Winfried K (2013). "Lethal dose". www.euronuclear.org. Archived from the original on 2018-08-04. Retrieved 2018-09-15.
  106. ↑ "Radiation Exposure - Dose and Dose Rate (the Gray & Sievert)". Ionactive. 2022-12-13. Retrieved 2024-07-27.
  107. ↑ Strey, Karsten (December 2019). "Die Gifte-Skala". Chemie in unserer Zeit. 53 (6): 386–399. doi:10.1002/ciuz.201900828. S2CID   199067092.
  108. ↑ Thirty-Two Years of Measurable Change Archived 2007-02-11 at the Wayback Machine
  109. ↑ van den Heuvel MJ, Clark DG, Fielder RJ, Koundakjian PP, Oliver GJ, Pelling D, et al. (July 1990). "The international validation of a fixed-dose procedure as an alternative to the classical LD50 test". Food and Chemical Toxicology. 28 (7): 469–482. doi:10.1016/0278-6915(90)90117-6. PMID   2210519.
  110. ↑ Lipnick RL, Cotruvo JA, Hill RN, Bruce RD, Stitzel KA, Walker AP, et al. (March 1995). "Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures". Food and Chemical Toxicology. 33 (3): 223–231. doi:10.1016/0278-6915(94)00136-c. PMID   7896233.
  111. ↑ Lichtman AH (August 1998). "The up-and-down method substantially reduces the number of animals required to determine antinociceptive ED50 values". Journal of Pharmacological and Toxicological Methods. 40 (2): 81–85. doi:10.1016/s1056-8719(98)00041-0. PMID   10100496.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.