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47-409: The median lethal dose, LD 50 (abbreviation for "lethal dose, 50%"), LC 50 (lethal concentration, 50%) or LCt 50 (lethal concentration and time) of a toxin , radiation , or pathogen is the dose required to kill half the members of a tested population after a specified test duration. LD 50 figures are frequently used as a general indicator of a substance's acute toxicity . A lower LD 50

94-470: A bee sting ) to potentially fatal even at extremely low doses (such as botulinum toxin ). Toxins are often distinguished from other chemical agents strictly based on their biological origin. Less strict understandings embrace naturally occurring inorganic toxins, such as arsenic . Other understandings embrace synthetic analogs of naturally occurring organic poisons as toxins, and may or may not embrace naturally occurring inorganic poisons. It

141-602: A revision in November 2018 that defines the kilogram by defining the Planck constant to be exactly 6.626 070 15 × 10  kg⋅m ⋅s , effectively defining the kilogram in terms of the second and the metre. The new definition took effect on 20 May 2019. Prior to the redefinition, the kilogram and several other SI units based on the kilogram were defined by a man-made metal artifact: the Kilogramme des Archives from 1799 to 1889, and

188-607: A cylinder composed of platinum–iridium , the International Prototype of the Kilogram (IPK), became the standard of the unit of mass for the metric system and remained so for 130 years, before the current standard was adopted in 2019 . The kilogram is defined in terms of three defining constants: The formal definition according to the General Conference on Weights and Measures (CGPM) is: The kilogram, symbol kg,

235-450: A given animal species under controlled conditions. The dosage is given per unit of bodyweight (typically stated in milligrams per kilogram ) of a substance known to have resulted in fatality in a particular species. When quoting an LD Lo , the particular species and method of administration ( e.g. ingested, inhaled, intravenous ) are typically stated. For gases and aerosols, lethal concentration (given in mg/m or ppm, parts per million)

282-481: A mass measurement instrument such as a Kibble balance as a primary standard for the kilogram mass. The kilogram was originally defined in 1795 during the French Revolution as the mass of one litre of water . The current definition of a kilogram agrees with this original definition to within 30 parts per million . In 1799, the platinum Kilogramme des Archives replaced it as the standard of mass. In 1889,

329-518: A safe level. In Europe, the European Food Safety Authority produced risk assessments for more than 4,000 substances in over 1,600 scientific opinions and they provide open access summaries of human health, animal health and ecological hazard assessments in their OpenFoodTox database. The OpenFoodTox database can be used to screen potential new foods for toxicity. The Toxicology and Environmental Health Information Program (TEHIP) at

376-425: A toxin delivered via a bite, sting, etc.). Poison is a related but broader term that encompasses both toxins and toxicants; poisons may enter the body through any means - typically inhalation , ingestion , or skin absorption . Toxin, toxicant, and poison are often used interchangeably despite these subtle differences in definition. The term toxungen has also been proposed to refer to toxins that are delivered onto

423-464: A very similar physiology, LD 50 results may or may not have equal bearing upon every mammal species, including humans. Animal-rights and animal-welfare groups, such as Animal Rights International, have campaigned against LD 50 testing on animals in particular as, in the case of some substances, causing the animals to die slow, painful deaths. Several countries, including the UK , have taken steps to ban

470-447: A weight measurement to a mass and therefore require precise measurement of the strength of gravity in laboratories ( gravimetry ). All approaches would have precisely fixed one or more constants of nature at a defined value. Because an SI unit may not have multiple prefixes (see SI prefix ), prefixes are added to gram , rather than the base unit kilogram , which already has a prefix as part of its name. For instance, one-millionth of

517-541: A written specification. At the 94th Meeting of the CIPM in 2005, it was recommended that the same be done with the kilogram. In October 2010, the CIPM voted to submit a resolution for consideration at the General Conference on Weights and Measures (CGPM), to "take note of an intention" that the kilogram be defined in terms of the Planck constant , h (which has dimensions of energy times time, thus mass × length / time) together with other physical constants. This resolution

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564-635: Is described as "a common informal name" on Russ Rowlett's Dictionary of Units of Measurement. When the United States Congress gave the metric system legal status in 1866, it permitted the use of the word kilo as an alternative to the word kilogram , but in 1990 revoked the status of the word kilo . The SI system was introduced in 1960 and in 1970 the BIPM started publishing the SI Brochure , which contains all relevant decisions and recommendations by

611-425: Is equivalent to 10 minutes of 10 mg/m (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 LC 50 and qualified by a duration of exposure (e.g., 10 minutes). The material safety data sheets for toxic substances frequently use this form of

658-461: Is important to confirm usage if a common understanding is critical. Toxins are a subset of toxicants . The term toxicant is preferred when the poison is man-made and therefore artificial. The human and scientific genetic assembly of a natural-based toxin should be considered a toxin as it is identical to its natural counterpart. The debate is one of linguistic semantics . The word toxin does not specify method of delivery (as opposed to venom ,

705-536: Is indicative of increased toxicity. The test was created by J.W. Trevan in 1927. The term "semilethal dose" is occasionally used with the same meaning, in particular in translations from non-English-language texts, but can also refer to a sub lethal dose; because of this ambiguity, it is usually avoided. LD 50 is usually determined by tests on animals such as laboratory mice . In 2011 the US Food and Drug Administration approved alternative methods to LD 50 for testing

752-410: Is known to be toxic to many animals . When used to test venom from venomous creatures, such as snakes , LD 50 results may be misleading due to the physiological differences between mice, rats, and humans. Many venomous snakes are specialized predators of mice, and their venom may be adapted specifically to incapacitate mice; and mongooses may be exceptionally resistant. While most mammals have

799-468: 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. 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,

846-603: Is the base unit of mass in the International System of Units (SI), having the unit symbol kg . 'Kilogram' means 'one thousand grams ' and is colloquially abbreviated to kilo . The kilogram is an SI base unit , defined ultimately in terms of three defining constants of the SI, namely a specific transition frequency of Cs, the speed of light, and the Planck constant. A properly equipped metrology laboratory can calibrate

893-400: Is the SI unit of mass. It is defined by taking the fixed numerical value of the Planck constant h to be 6.626 070 15 × 10 when expressed in the unit J⋅s, which is equal to kg⋅m ⋅s , where the metre and the second are defined in terms of c and Δ ν Cs . Defined in term of those units, the kg is formulated as: This definition is generally consistent with previous definitions:

940-402: Is the analogous concept, although this also depends on the duration of exposure, which has to be included in the definition. The term incipient lethal level is used to describe a LC 50 value that is independent of time. A comparable measurement is LCt 50 , which relates to lethal dosage from exposure, where C is concentration and t is time. It is often expressed in terms of mg-min/m LCt 50

987-470: 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/m

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1034-514: Is to use model organisms , particularly animals like mice or rats, converting to dosage per kilogram of biomass, and extrapolating to human norms. The degree of error from animal-extrapolated LD values is large. The biology of test animals differs in important aspects to that of humans. For instance, mouse tissue is approximately fifty times less responsive than human tissue to the venom of the Sydney funnel-web spider . The square–cube law also complicates

1081-514: The CGPM concerning units. The SI Brochure states that "It is not permissible to use abbreviations for unit symbols or unit names ...". For use with east Asian character sets, the SI symbol is encoded as a single Unicode character, U+338F ㎏ SQUARE KG in the CJK Compatibility block. The replacement of the International Prototype of the Kilogram (IPK) as the primary standard

1128-471: The United States National Library of Medicine (NLM) maintains a comprehensive toxicology and environmental health web site that includes access to toxins-related resources produced by TEHIP and by other government agencies and organizations. This web site includes links to databases, bibliographies, tutorials, and other scientific and consumer-oriented resources. TEHIP also is responsible for

1175-552: The mass remains within 30 ppm of the mass of one litre of water. The kilogram is the only base SI unit with an SI prefix ( kilo ) as part of its name. The word kilogramme or kilogram is derived from the French kilogramme , which itself was a learned coinage, prefixing the Greek stem of χίλιοι khilioi "a thousand" to gramma , a Late Latin term for "a small weight", itself from Greek γράμμα . The word kilogramme

1222-574: The French word kilo , a shortening of kilogramme , was imported into the English language where it has been used to mean both kilogram and kilometre. While kilo as an alternative is acceptable, to The Economist for example, the Canadian government's Termium Plus system states that "SI (International System of Units) usage, followed in scientific and technical writing" does not allow its usage and it

1269-462: The IPK from 1889 to 2019. In 1960, the metre , previously similarly having been defined with reference to a single platinum-iridium bar with two marks on it, was redefined in terms of an invariant physical constant (the wavelength of a particular emission of light emitted by krypton , and later the speed of light ) so that the standard can be independently reproduced in different laboratories by following

1316-462: The LD 50 . Measures such as "LD 1 " and "LD 99 " (dosage required to kill 1% or 99%, respectively, of the test population) are occasionally used for specific purposes. 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, LD 50 figures are often qualified with

1363-714: The Toxicology Data Network (TOXNET), an integrated system of toxicology and environmental health databases that are available free of charge on the web. TOXMAP is a Geographic Information System (GIS) that is part of TOXNET. TOXMAP uses maps of the United States to help users visually explore data from the United States Environmental Protection Agency 's (EPA) Toxics Release Inventory and Superfund Basic Research Programs . Kilogram The kilogram (also spelled kilogramme )

1410-689: The biological origin as opposed to environmental or anthropogenic origins. Biotoxins can be classified by their mechanism of delivery as poisons (passively transferred via ingestion, inhalation, or absorption across the skin), toxungens (actively transferred to the target's surface by spitting, spraying, or smearing), or venoms (delivered through a wound generated by a bite, sting, or other such action). They can also be classified by their source, such as fungal biotoxins , microbial toxins , plant biotoxins , or animal biotoxins. Toxins produced by microorganisms are important virulence determinants responsible for microbial pathogenicity and/or evasion of

1457-428: The body surface of another organism without an accompanying wound . A rather informal terminology of individual toxins relates them to the anatomical location where their effects are most notable: On a broader scale, toxins may be classified as either exotoxins , excreted by an organism, or endotoxins , which are released mainly when bacteria are lysed . The term "biotoxin" is sometimes used to explicitly confirm

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1504-456: The cosmetic drug Botox without animal tests. The LD 50 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, but stated as nanograms (suitable for botulinum ), micrograms, milligrams, or grams (suitable for paracetamol ) per kilogram. Stating it this way allows the relative toxicity of different substances to be compared, and normalizes for

1551-414: The difficulties in counting actual organisms in a dose, infective doses may be expressed in terms of biological assay, such as the number of LD 50 's to some test animal. In biological warfare infective dosage is the number of infective doses per minute for a cubic meter (e.g., ICt 50 is 100 medium doses - min/m).) The lowest lethal dose (LD Lo ) is the least amount of drug that can produce death in

1598-459: The host immune response . Biotoxins vary greatly in purpose and mechanism, and can be highly complex (the venom of the cone snail can contain over 100 unique peptides , which target specific nerve channels or receptors). Biotoxins in nature have two primary functions: Some of the more well known types of biotoxins include: Many living organisms employ toxins offensively or defensively. A relatively small number of toxins are known to have

1645-461: The mode of administration, e.g., "LD 50 i.v." The related quantities LD 50 /30 or LD 50 /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 with radiation , as survival beyond 60 days usually results in recovery. LD values for humans are best estimated by extrapolating results from human cell cultures . One form of measuring LD

1692-803: The oral LD 50 , and the Organisation for Economic Co-operation and Development (OECD) abolished the requirement for the oral test in 2001. Toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms . They occur especially as proteins , often conjugated . The term was first used by organic chemist Ludwig Brieger (1849–1919), derived from toxic . Toxins can be small molecules , peptides , or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors . They vary greatly in their toxicity , ranging from usually minor (such as

1739-714: The potential to cause widespread sickness or casualties. They are often inexpensive and easily available, and in some cases it is possible to refine them outside the laboratory. As biotoxins act quickly, and are highly toxic even at low doses, they can be more efficient than chemical agents. Due to these factors, it is vital to raise awareness of the clinical symptoms of biotoxin poisoning, and to develop effective countermeasures including rapid investigation, response, and treatment. The term "environmental toxin" can sometimes explicitly include synthetic contaminants such as industrial pollutants and other artificially made toxic substances. As this contradicts most formal definitions of

1786-500: The reproducible production of new, kilogram-mass prototypes on demand (albeit with extraordinary effort) using measurement techniques and material properties that are ultimately based on, or traceable to, physical constants. Others were based on devices that measured either the acceleration or weight of hand-tuned kilogram test masses and that expressed their magnitudes in electrical terms via special components that permit traceability to physical constants. All approaches depend on converting

1833-427: The scaling relationships involved. Researchers are shifting away from animal-based LD measurements in some instances. The U.S. Food and Drug Administration has begun to approve more non-animal methods in response to animal welfare concerns. The median infective dose (ID 50 ) 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

1880-449: The term "toxin", it is important to confirm what the researcher means when encountering the term outside of microbiological contexts. Environmental toxins from food chains that may be dangerous to human health include: In general, when scientists determine the amount of a substance that may be hazardous for humans, animals and/or the environment they determine the amount of the substance likely to trigger effects and if possible establish

1927-461: The term even if the substance does follow Haber's Law. The LC Lo is the lowest concentration of a chemical, given over a period of time, that results in the fatality of an individual animal. LC Lo is typically for an acute (<24 hour) exposure. It is related to the LC 50 , the median lethal concentration. The LC Lo is used for gases and aerosolized material. As a measure of toxicity, lethal dose

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1974-433: The variation in the size of the animals exposed, although toxicity does not always scale simply with body mass. 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 LD 50 is not the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than

2021-604: Was accepted by the 24th conference of the CGPM in October 2011 and further discussed at the 25th conference in 2014. Although the Committee recognised that significant progress had been made, they concluded that the data did not yet appear sufficiently robust to adopt the revised definition, and that work should continue to enable the adoption at the 26th meeting, scheduled for 2018. Such a definition would theoretically permit any apparatus that

2068-515: Was adopted in Great Britain when the word was used for the first time in English in 1795, with the spelling kilogram being adopted in the United States. In the United Kingdom both spellings are used, with "kilogram" having become by far the more common. UK law regulating the units to be used when trading by weight or measure does not prevent the use of either spelling. In the 19th century

2115-410: Was capable of delineating the kilogram in terms of the Planck constant to be used as long as it possessed sufficient precision, accuracy and stability. The Kibble balance is one way to do this. As part of this project, a variety of very different technologies and approaches were considered and explored over many years. Some of these approaches were based on equipment and procedures that would enable

2162-525: Was motivated by evidence accumulated over a long period of time that the mass of the IPK and its replicas had been changing; the IPK had diverged from its replicas by approximately 50 micrograms since their manufacture late in the 19th century. This led to several competing efforts to develop measurement technology precise enough to warrant replacing the kilogram artefact with a definition based directly on physical fundamental constants. The International Committee for Weights and Measures (CIPM) approved

2209-565: Was written into French law in 1795, in the Decree of 18 Germinal , which revised the provisional system of units introduced by the French National Convention two years earlier, where the gravet had been defined as weight ( poids ) of a cubic centimetre of water, equal to 1/1000 of a grave . In the decree of 1795, the term gramme thus replaced gravet , and kilogramme replaced grave . The French spelling

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