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68-461: Detoxification or detoxication ( detox for short) is the physiological or medicinal removal of toxic substances from a living organism , including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of drug withdrawal during which an organism returns to homeostasis after long-term use of an addictive substance. In medicine , detoxification can be achieved by decontamination of poison ingestion and

136-529: A 14-day period; or causes inflammation which lasts for 14 days in two test subjects. Mild skin irritation is minor damage (less severe than irritation) within 72 hours of application or for three consecutive days after application. Serious eye damage involves tissue damage or degradation of vision which does not fully reverse in 21 days. Eye irritation involves changes to the eye which do fully reverse within 21 days. An Environmental hazard can be defined as any condition, process, or state adversely affecting

204-401: A broad sense but are generally called pathogens rather than toxicants. The biological toxicity of pathogens can be difficult to measure because the threshold dose may be a single organism. Theoretically one virus , bacterium or worm can reproduce to cause a serious infection . If a host has an intact immune system , the inherent toxicity of the organism is balanced by the host's response;

272-478: A common reason for hazardous drug interactions . These pathways are also important in environmental science , with the xenobiotic metabolism of microorganisms determining whether a pollutant will be broken down during bioremediation , or persist in the environment. The enzymes of xenobiotic metabolism, particularly the glutathione S-transferases are also important in agriculture, since they may produce resistance to pesticides and herbicides . Drug metabolism

340-653: A community program that lasts several months and takes place in a residential setting rather than in a medical center. Drug detoxification varies depending on the location of treatment, but most detox centers provide treatment to avoid the symptoms of physical withdrawal from alcohol and from other drugs. Most also incorporate counseling and therapy during detox to help with the consequences of withdrawal. An animal's metabolism can produce harmful substances which it can then make less toxic through reduction , oxidation (collectively known as redox reactions), conjugation and excretion of molecules from cells or tissues. This

408-424: A deeply rooted history of not only being aware of toxicity, but also taking advantage of it as a tool. Archaeologists studying bone arrows from caves of Southern Africa have noted the likelihood that some aging 72,000 to 80,000 years old were dipped in specially prepared poisons to increase their lethality. Although scientific instrumentation limitations make it difficult to prove concretely, archaeologists hypothesize

476-415: A dose, whereas for even a very toxic substance such as snake venom there is a dose below which there is no detectable toxic effect. Toxicity is species-specific, making cross-species analysis problematic. Newer paradigms and metrics are evolving to bypass animal testing , while maintaining the concept of toxicity endpoints. In Ancient Greek medical literature, the adjective τoξικόν (meaning "toxic")

544-414: A given disorder (DiMascio, Soltys and Shader, 1970). These undesirable effects include anticholinergic effects, alpha-adrenergic blockade, and dopaminergic effects, among others. Toxicity can be measured by its effects on the target (organism, organ, tissue or cell). Because individuals typically have different levels of response to the same dose of a toxic substance, a population-level measure of toxicity

612-519: A group of people who acetylate slowly ( slow acetylators ) and those who acetylate quickly ( rapid acetylators ), split roughly 50:50 in the population of Canada. However, variability in NAT2 alleles distribution across different populations is high and some ethnicities have higher proportion of slow acetylators. This variation in metabolising capacity may have dramatic consequences, as the slow acetylators are more prone to dose-dependent toxicity. NAT2 enzyme

680-487: A hatter" and the "Mad Hatter" of the book Alice in Wonderland derive from the known occupational toxicity of hatters who used a toxic chemical for controlling the shape of hats. Exposure to chemicals in the workplace environment may be required for evaluation by industrial hygiene professionals. Hazards in the arts have been an issue for artists for centuries, even though the toxicity of their tools, methods, and materials

748-470: A large group of broad-specificity transferases, which in combination can metabolise almost any hydrophobic compound that contains nucleophilic or electrophilic groups. One of the most important classes of this group is that of the glutathione S-transferases (GSTs). After phase II reactions, the xenobiotic conjugates may be further metabolized. A common example is the processing of glutathione conjugates to acetylcysteine (mercapturic acid) conjugates. Here,

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816-553: A molecule of formaldehyde , while oxidation of the O-methyl groups takes place to a lesser extent. Cytochrome P450 reductase, also known as NADPH:ferrihemoprotein oxidoreductase, NADPH:hemoprotein oxidoreductase, NADPH:P450 oxidoreductase, P450 reductase, POR, CPR, CYPOR, is a membrane-bound enzyme required for electron transfer to cytochrome P450 in the microsome of the eukaryotic cell from a FAD- and FMN-containing enzyme NADPH:cytochrome P450 reductase The general scheme of electron flow in

884-722: A new method of non-toxic lithography . There are many environmental health mapping tools. TOXMAP is a Geographic Information System (GIS) from the Division of Specialized Information Services of the United States National Library of Medicine (NLM) that 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 programs. TOXMAP

952-399: A newly synthesized and previously unstudied chemical that is believed to be very similar in effect to another compound could be assigned an additional protection factor of 10 to account for possible differences in effects that are probably much smaller. This approach is very approximate, but such protection factors are deliberately very conservative, and the method has been found to be useful in

1020-482: A pharmacologically inactive compound (a prodrug ) to a pharmacologically active one. By the same token, Phase I can turn a nontoxic molecule into a poisonous one ( toxification ). Simple hydrolysis in the stomach is normally an innocuous reaction, however there are exceptions. For example, phase I metabolism converts acetonitrile to HOCH 2 CN, which rapidly dissociates into formaldehyde and hydrogen cyanide . Phase I metabolism of drug candidates can be simulated in

1088-487: A physical toxicant if taken in extremely high doses because the concentration of vital ions decreases dramatically with too much water in the body. Asphyxiant gases can be considered physical toxicants because they act by displacing oxygen in the environment but they are inert, not chemically toxic gases. Radiation can have a toxic effect on organisms. Behavioral toxicity refers to the undesirable effects of essentially therapeutic levels of medication clinically indicated for

1156-474: A screening tool. Drug metabolism The metabolism of pharmaceutical drugs is an important aspect of pharmacology and medicine . For example, the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. Drug metabolism also affects multidrug resistance in infectious diseases and in chemotherapy for cancer , and the actions of some drugs as substrates or inhibitors of enzymes involved in xenobiotic metabolism are

1224-516: A toxic substance is safe for a laboratory rat, one might assume that one-tenth that dose would be safe for a human, allowing a safety factor of 10 to allow for interspecies differences between two mammals; if the data are from fish, one might use a factor of 100 to account for the greater difference between two chordate classes (fish and mammals). Similarly, an extra protection factor may be used for individuals believed to be more susceptible to toxic effects such as in pregnancy or with certain diseases. Or,

1292-586: A very limited number of cases) chelation therapy . There is a firm scientific base in evidence-based medicine for this treatment. Alcohol detoxification is a process by which a heavy drinker's system is brought back to normal after being habituated to having alcohol in the body continuously for an extended period of substance abuse. Serious alcohol addiction results in a downregulation of GABA neurotransmitter receptors. Precipitous withdrawal from long-term alcohol addiction without medical management can cause severe health problems and can be fatal. Alcohol detox

1360-400: A wide variety of applications. Assessing all aspects of the toxicity of cancer-causing agents involves additional issues, since it is not certain if there is a minimal effective dose for carcinogens , or whether the risk is just too small to see. In addition, it is possible that a single cell transformed into a cancer cell is all it takes to develop the full effect (the "one hit" theory). It

1428-855: Is a crucial pathway in this regard. In general, anything that increases the rate of metabolism (e.g., enzyme induction ) of a pharmacologically active metabolite will decrease the duration and intensity of the drug action. The opposite is also true, as in enzyme inhibition . However, in cases where an enzyme is responsible for metabolizing a pro-drug into a drug, enzyme induction can accelerate this conversion and increase drug levels, potentially causing toxicity. Various physiological and pathological factors can also affect drug metabolism. Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics ), enterohepatic circulation , nutrition , sex differences or gut microbiota . This last factor has significance because gut microorganisms are able to chemically modify

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1496-489: Is a primary metaboliser of antituberculosis ( isoniazid ), some antihypertensive ( hydralazine ), anti-arrythmic drugs ( procainamide ), antidepressants ( phenelzine ) and many more and increased toxicity as well as drug adverse reactions in slow acetylators have been widely reported. Similar phenomenons of altered metabolism due to inherited variations have been described for other drug-metabolising enzymes, like CYP2D6 , CYP3A4 , DPYD , UGT1A1 . DPYD and UGT1A1 genotyping

1564-584: Is a resource funded by the US Federal Government. TOXMAP's chemical and environmental health information is taken from NLM's Toxicology Data Network (TOXNET) and PubMed , and from other authoritative sources. Aquatic toxicity testing subjects key indicator species of fish or crustacea to certain concentrations of a substance in their environment to determine the lethality level. Fish are exposed for 96 hours while crustacea are exposed for 48 hours. While GHS does not define toxicity past 100 mg/L,

1632-570: Is an elegant combination of physical barriers and low-specificity enzymatic systems. All organisms use cell membranes as hydrophobic permeability barriers to control access to their internal environment. Polar compounds cannot diffuse across these cell membranes, and the uptake of useful molecules is mediated through transport proteins that specifically select substrates from the extracellular mixture. This selective uptake means that most hydrophilic molecules cannot enter cells, since they are not recognised by any specific transporters. In contrast,

1700-419: Is called xenobiotic metabolism . Enzymes that are important in detoxification metabolism include cytochrome P450 oxidases , UDP-glucuronosyltransferases , and glutathione S -transferases . These processes are particularly well-studied as part of drug metabolism , as they influence the pharmacokinetics of a drug in the body. Certain approaches in alternative medicine claim to remove alleged "toxins" from

1768-616: Is divided into three phases. In phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics. These modified compounds are then conjugated to polar compounds in phase II reactions. These reactions are catalysed by transferase enzymes such as glutathione S-transferases. Finally, in phase III, the conjugated xenobiotics may be further processed, before being recognised by efflux transporters and pumped out of cells. Drug metabolism often converts lipophilic compounds into hydrophilic products that are more readily excreted . The exact compounds an organism

1836-414: Is exposed to will be largely unpredictable, and may differ widely over time; these are major characteristics of xenobiotic toxic stress. The major challenge faced by xenobiotic detoxification systems is that they must be able to remove the almost-limitless number of xenobiotic compounds from the complex mixture of chemicals involved in normal metabolism . The solution that has evolved to address this problem

1904-440: Is incurred and how long it remains; whether it is reversible and how many test subjects were affected. Skin corrosion from a substance must penetrate through the epidermis into the dermis within four hours of application and must not reverse the damage within 14 days. Skin irritation shows damage less severe than corrosion if: the damage occurs within 72 hours of application; or for three consecutive days after application within

1972-543: Is more difficult to determine the toxicity of chemical mixtures than a pure chemical because each component displays its own toxicity, and components may interact to produce enhanced or diminished effects. Common mixtures include gasoline , cigarette smoke , and industrial waste . Even more complex are situations with more than one type of toxic entity, such as the discharge from a malfunctioning sewage treatment plant, with both chemical and biological agents. The preclinical toxicity testing on various biological systems reveals

2040-566: Is not a treatment for alcoholism . After detoxification, other treatments must be undertaken to deal with the underlying addiction that caused alcohol use. Clinicians use drug detoxification to reduce or relieve withdrawal symptoms while helping an addicted person adjust to living without drug use. Drug detoxification does not aim to treat addiction but rather represents an early step within long-term treatment. Detoxification may be achieved drug-free or may use medications as an aspect of treatment. Often drug detoxification and treatment will occur in

2108-786: Is now required before administration of the corresponding substrate compounds ( 5-FU and capecitabine for DPYD and irinotecan for UGT1A1) to determine the activity of DPYD and UGT1A1 enzyme and reduce the dose of the drug in order to avoid severe adverse reactions. Dose, frequency, route of administration, tissue distribution and protein binding of the drug affect its metabolism. Pathological factors can also influence drug metabolism, including liver , kidney , or heart diseases. In silico modelling and simulation methods allow drug metabolism to be predicted in virtual patient populations prior to performing clinical studies in human subjects. This can be used to identify individuals most at risk from adverse reaction. Studies on how people transform

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2176-445: Is often used which relates the probabilities of an outcome for a given individual in a population. One such measure is the LD 50 . When such data does not exist, estimates are made by comparison to known similar toxic things, or to similar exposures in similar organisms. Then, " safety factors " are added to account for uncertainties in data and evaluation processes. For example, if a dose of

2244-422: Is the result of these species' being derived from normal cellular constituents and usually sharing their polar characteristics. However, since these compounds are few in number, it is possible for enzymatic systems to utilize specific molecular recognition to recognize and remove them. The similarity of these molecules to useful metabolites therefore means that different detoxification enzymes are usually required for

2312-417: The first pass effect . Other sites of drug metabolism include epithelial cells of the gastrointestinal tract , lungs , kidneys , and the skin . These sites are usually responsible for localized toxicity reactions. The duration and intensity of pharmacological action of most lipophilic drugs are determined by the rate they are metabolized to inactive products. The Cytochrome P450 monooxygenase system

2380-477: The γ-glutamate and glycine residues in the glutathione molecule are removed by gamma-glutamyl transpeptidase and dipeptidases . In the final step, the cysteine residue in the conjugate is acetylated . Conjugates and their metabolites can be excreted from cells in phase III of their metabolism, with the anionic groups acting as affinity tags for a variety of membrane transporters of the multidrug resistance protein (MRP) family. These proteins are members of

2448-457: The EPA currently lists aquatic toxicity as "practically non-toxic" in concentrations greater than 100 ppm. Note: A category 4 is established for chronic exposure, but simply contains any toxic substance which is mostly insoluble, or has no data for acute toxicity. Toxicity of a substance can be affected by many different factors, such as the pathway of administration (whether the toxicant is applied to

2516-546: The No Observed Adverse Effect Level (NOAEL) dose and is helpful for clinical studies. For substances to be regulated and handled appropriately they must be properly classified and labelled. Classification is determined by approved testing measures or calculations and has determined cut-off levels set by governments and scientists (for example, no-observed-adverse-effect levels , threshold limit values , and tolerable daily intake levels). Pesticides provide

2584-1036: The POR/P450 system is: NADPH → FAD → FMN → P450 → O 2 During reduction reactions, a chemical can enter futile cycling , in which it gains a free-radical electron, then promptly loses it to oxygen (to form a superoxide anion ). In subsequent phase II reactions, these activated xenobiotic metabolites are conjugated with charged species such as glutathione (GSH), sulfate , glycine , or glucuronic acid . Sites on drugs where conjugation reactions occur include carboxy (-COOH), hydroxy (-OH), amino (NH 2 ), and thiol (-SH) groups. Products of conjugation reactions have increased molecular weight and tend to be less active than their substrates, unlike Phase I reactions which often produce active metabolites . The addition of large anionic groups (such as GSH) detoxifies reactive electrophiles and produces more polar metabolites that cannot diffuse across membranes, and may, therefore, be actively transported. These reactions are catalysed by

2652-442: The body and cause malaise . Such alternative therapies include contrast showers , detoxification foot pads , oil pulling , Gerson therapy , snake-stones , body cleansing , Scientology 's and Narconon 's Purification Rundown , water fasting , and metabolic therapy . Toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism . Toxicity can refer to

2720-548: The body through herbal, electrical, electromagnetic or other treatments. These toxins may not be linked to symptoms and treatments have no scientific evidence, making the validity of such techniques questionable. There is little evidence for toxic accumulation in these cases, as the liver and kidneys automatically detoxify and excrete many toxic materials including metabolic wastes. Under this theory, if toxins are too rapidly released without being safely eliminated (such as when metabolizing fat that stores toxins), they can damage

2788-652: The diffusion of hydrophobic compounds across these barriers cannot be controlled, and organisms, therefore, cannot exclude lipid -soluble xenobiotics using membrane barriers. However, the existence of a permeability barrier means that organisms were able to evolve detoxification systems that exploit the hydrophobicity common to membrane-permeable xenobiotics. These systems therefore solve the specificity problem by possessing such broad substrate specificities that they metabolise almost any non-polar compound. Useful metabolites are excluded since they are polar, and in general contain one or more charged groups. The detoxification of

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2856-465: 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. A central concept of toxicology is that the effects of a toxicant are dose -dependent; even water can lead to water intoxication when taken in too high

2924-775: The effective toxicity is then a combination. In some cases, e.g. cholera toxin , the disease is chiefly caused by a nonliving substance secreted by the organism, rather than the organism itself. Such nonliving biological toxicants are generally called toxins if produced by a microorganism, plant, or fungus, and venoms if produced by an animal. Physical toxicants are substances that, due to their physical nature, interfere with biological processes. Examples include coal dust, asbestos fibres or finely divided silicon dioxide , all of which can ultimately be fatal if inhaled. Corrosive chemicals possess physical toxicity because they destroy tissues, but are not directly poisonous unless they interfere directly with biological activity. Water can act as

2992-467: The endoplasmic reticulum of cells) proteins such as CYP enzymes . In cases of kidney failure , the action of the kidneys is mimicked by dialysis ; kidney and liver transplants are also used for kidney and liver failure, respectively. Heavy metal detox , or detoxification , is the removal of toxic heavy metal substances from the body. In conventional medicine , detoxification can also be achieved artificially by techniques such as dialysis and (in

3060-460: The entire body, lethality to specific organs, major/minor damage, or cause cancer. These are globally accepted definitions of what toxicity is. Anything falling outside of the definition cannot be classified as that type of toxicant. Acute toxicity looks at lethal effects following oral, dermal or inhalation exposure. It is split into five categories of severity where Category 1 requires the least amount of exposure to be lethal and Category 5 requires

3128-419: The environment. These hazards can be physical or chemical, and present in air, water, and/or soil. These conditions can cause extensive harm to humans and other organisms within an ecosystem. The EPA maintains a list of priority pollutants for testing and regulation. Workers in various occupations may be at a greater level of risk for several types of toxicity, including neurotoxicity. The expression "Mad as

3196-572: The example of well-established toxicity class systems and toxicity labels . While currently many countries have different regulations regarding the types of tests, numbers of tests and cut-off levels, the implementation of the Globally Harmonized System has begun unifying these countries. Global classification looks at three areas: Physical Hazards (explosions and pyrotechnics), Health Hazards and environmental hazards . The types of toxicities where substances may cause lethality to

3264-476: The family of ATP-binding cassette transporters and can catalyse the ATP-dependent transport of a huge variety of hydrophobic anions, and thus act to remove phase II products to the extracellular medium, where they may be further metabolized or excreted. The detoxification of endogenous reactive metabolites such as peroxides and reactive aldehydes often cannot be achieved by the system described above. This

3332-598: The generation of a highly-reactive oxyferryl species, according to the following scheme: Phase I reactions (also termed nonsynthetic reactions) may occur by oxidation , reduction , hydrolysis , cyclization , decyclization, and addition of oxygen or removal of hydrogen, carried out by mixed function oxidases, often in the liver. These oxidative reactions typically involve a cytochrome P450 monooxygenase (often abbreviated CYP), NADPH and oxygen. The classes of pharmaceutical drugs that utilize this method for their metabolism include phenothiazines , paracetamol , and steroids. If

3400-433: The genetic makeup of an individual, an individual's overall health, and many others. Several of the terms used to describe these factors have been included here. Considering the limitations of the dose-response concept, a novel Abstract Drug Toxicity Index (DTI) has been proposed recently. DTI redefines drug toxicity, identifies hepatotoxic drugs, gives mechanistic insights, predicts clinical outcomes and has potential as

3468-419: The investigation of the enzymes and pathways that were responsible for the production of these metabolites. This field became defined as a separate area of study with the publication by Richard Williams of the book Detoxication mechanisms in 1947. This modern biochemical research resulted in the identification of glutathione S -transferases in 1961, followed by the discovery of cytochrome P450s in 1962, and

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3536-456: The laboratory using non-enzyme catalysts. This example of a biomimetic reaction tends to give products that often contains the Phase I metabolites. As an example, the major metabolite of the pharmaceutical trimebutine , desmethyltrimebutine (nor-trimebutine), can be efficiently produced by in vitro oxidation of the commercially available drug. Hydroxylation of an N-methyl group leads to expulsion of

3604-454: The liver's contribution to drug metabolism include that it is a large organ, that it is the first organ perfused by chemicals absorbed in the gut , and that there are very high concentrations of most drug-metabolizing enzyme systems relative to other organs. If a drug is taken into the GI tract, where it enters hepatic circulation through the portal vein , it becomes well-metabolized and is said to show

3672-483: The metabolism of each group of endogenous toxins. Examples of these specific detoxification systems are the glyoxalase system , which acts to dispose of the reactive aldehyde methylglyoxal , and the various antioxidant systems that remove reactive oxygen species . Quantitatively, the smooth endoplasmic reticulum of the liver cell is the principal organ of drug metabolism, although every biological tissue has some ability to metabolize drugs. Factors responsible for

3740-428: The metabolites of phase I reactions are sufficiently polar, they may be readily excreted at this point. However, many phase I products are not eliminated rapidly and undergo a subsequent reaction in which an endogenous substrate combines with the newly incorporated functional group to form a highly polar conjugate. A common Phase I oxidation involves conversion of a C-H bond to a C-OH. This reaction sometimes converts

3808-478: The most common modifications is hydroxylation catalysed by the cytochrome P-450-dependent mixed-function oxidase system . These enzyme complexes act to incorporate an atom of oxygen into nonactivated hydrocarbons, which can result in either the introduction of hydroxyl groups or N-, O- and S-dealkylation of substrates. The reaction mechanism of the P-450 oxidases proceeds through the reduction of cytochrome-bound oxygen and

3876-406: The most exposure to be lethal. The table below shows the upper limits for each category. Note: The undefined values are expected to be roughly equivalent to the category 5 values for oral and dermal administration. Skin corrosion and irritation are determined through a skin patch test analysis, similar to an allergic inflammation patch test . This examines the severity of the damage done; when it

3944-544: The practice of making poison arrows was widespread in cultures as early as the paleolithic era. The San people of Southern Africa have managed to preserved this practice into the modern era, with the knowledge base to form complex mixtures from poisonous beetles and plant derived extracts, yielding an arrow-tip product with a shelf life beyond several months to a year. There are generally five types of toxicities: chemical, biological, physical, radioactive and behavioural. Disease-causing microorganisms and parasites are toxic in

4012-419: The reactive aldehyde methylglyoxal, and the various antioxidant systems that eliminate reactive oxygen species . The metabolism of xenobiotics is often divided into three phases: modification, conjugation, and excretion. These reactions act in concert to detoxify xenobiotics and remove them from cells. In phase I, a variety of enzymes act to introduce reactive and polar groups into their substrates. One of

4080-401: The reactive by-products of normal metabolism cannot be achieved by the systems outlined above, because these species are derived from normal cellular constituents and usually share their polar characteristics. However, since these compounds are few in number, specific enzymes can recognize and remove them. Examples of these specific detoxification systems are the glyoxalase system , which removes

4148-406: The skin, ingested, inhaled, injected), the time of exposure (a brief encounter or long term), the number of exposures (a single dose or multiple doses over time), the physical form of the toxicant (solid, liquid, gas), the concentration of the substance, and in the case of gases, the partial pressure (at high ambient pressure, partial pressure will increase for a given concentration as a gas fraction),

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4216-456: The species-, organ- and dose-specific toxic effects of an investigational product. The toxicity of substances can be observed by (a) studying the accidental exposures to a substance (b) in vitro studies using cells/ cell lines (c) in vivo exposure on experimental animals. Toxicity tests are mostly used to examine specific adverse events or specific endpoints such as cancer, cardiotoxicity, and skin/eye irritation. Toxicity testing also helps calculate

4284-747: The structure of drugs through degradation and biotransformation processes, thus altering the activity and toxicity of drugs. These processes can decrease the efficacy of drugs, as is the case of digoxin in the presence of Eggerthella lenta in the microbiota. Genetic variation ( polymorphism ) accounts for some of the variability in the effect of drugs. In general, drugs are metabolized more slowly in fetal , neonatal and elderly humans and animals than in adults . Inherited genetic variations in drug metabolising enzymes result in their different catalytic activity levels. For example, N-acetyltransferases (involved in Phase II reactions), individual variation creates

4352-426: The substances that they ingest began in the mid-nineteenth century, with chemists discovering that organic chemicals such as benzaldehyde could be oxidized and conjugated to amino acids in the human body. During the remainder of the nineteenth century, several other basic detoxification reactions were discovered, such as methylation , acetylation , and sulfonation . In the early twentieth century, work moved on to

4420-494: The use of antidotes as well as techniques such as dialysis and (in a limited number of cases) chelation therapy . Many alternative medicine practitioners promote various types of detoxification such as detoxification diets . Sense about Science , a UK-based charitable trust, determined that most such dietary "detox" claims lack any supporting evidence. The liver and kidney are naturally capable of detox, as are intracellular (specifically, inner membrane of mitochondria or in

4488-458: Was not always adequately realized. Lead and cadmium, among other toxic elements, were often incorporated into the names of artist's oil paints and pigments, for example, "lead white" and "cadmium red". 20th-century printmakers and other artists began to be aware of the toxic substances, toxic techniques, and toxic fumes in glues, painting mediums, pigments, and solvents, many of which in their labelling gave no indication of their toxicity. An example

4556-448: Was the use of xylol for cleaning silk screens . Painters began to notice the dangers of breathing painting mediums and thinners such as turpentine . Aware of toxicants in studios and workshops, in 1998 printmaker Keith Howard published Non-Toxic Intaglio Printmaking which detailed twelve innovative Intaglio -type printmaking techniques including photo etching , digital imaging , acrylic -resist hand-etching methods, and introducing

4624-546: Was used to describe substances which had the ability of "causing death or serious debilitation or exhibiting symptoms of infection." The word draws its origins from the Greek noun τόξον toxon (meaning "arc"), in reference to the use of bows and poisoned arrows as weapons. English-speaking American culture has adopted several figurative usages for toxicity , often when describing harmful inter-personal relationships or character traits (e.g. " toxic masculinity "). Humans have

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