Toxication, toxification or toxicity exaltation is the conversion of a

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

into a more toxic form in living organisms or in substrates such as

soil Soil, also commonly referred to as earth or dirt, is a mixture of organic matter, minerals, gases, liquids, and organisms that together support life. Some scientific definitions distinguish ''dirt'' from ''soil'' by restricting the former te ...

water Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as a ...

. The conversion can be caused by

enzymatic Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

in the organisms, as well as by

abiotic In biology and ecology, abiotic components or abiotic factors are non-living chemical and physical parts of the environment that affect living organisms and the functioning of ecosystems. Abiotic factors and the phenomena associated with them under ...

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

s. While the parent drug are usually less active, both the parent drug and its metabolite can be chemically active and cause

toxicity 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 subst ...

, leading to mutagenesis, teratogenesis, and carcinogenesis. Different classes of enzymes, such as P450-monooxygenases, epoxide hydrolase, or acetyltransferases can catalyze the process in the cell, mostly in the liver. Parent non-toxic chemicals are generally referred to as ''protoxins''. While toxication is generally undesirable, in certain cases it is required for the ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' conversion of a

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

to a metabolite with desired pharmacological or toxicological activity.

Codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

is an example of a prodrug, metabolized in the body to the active compounds

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

and codeine-6-glucuronide. Heavy metals are also the root cause for intoxication. Heavy metals such as lead, nickel, aluminium, cobalt, copper sometimes act as pseudo elements in biological system, the toxicity of heavy metal depends on the intake of the compounds present in the environment. Depending on the exposure and intake of the heavy metals there are two types of diseases i.e., acute and chronic. When a person starts accumulating heavy metals, leads to chronic disease like liver failure, heart diseases etc. Using pesticides is also one of the reason for the cause for toxication. Pesticides which possess elements like calcium, lead, copper, and zinc reside at the end of usage in the soil, which affects the fertility of the soil

Toxication by enzymatic metabolism

CYP450 enzymes

Phase I of

drug metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of ...

are bioactivation pathways, which are catalyzed by CYP450 enzymes, produce toxic metabolites and thus have the potential to damage cells. The unusual level of activity CYP450 enzymes might lead to the changes in drug metabolism and convert drugs into their more toxic forms. Among Phase I CYP450 enzymes, the subfamilies CYP2D6 and CYP3A are responsible for

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...

during drug metabolism with a number of different drugs, including flucloxacilin, trioleandomycin, and troglitazone. Hepatotoxicity indicates the drug's toxicity to liver.

Paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...

(acetaminophen, APAP) is converted into the hepatotoxic metabolite

NAPQI NAPQI, also known as NAPBQI or ''N''-acetyl-''p''-benzoquinone imine, is a toxic byproduct produced during the xenobiotic metabolism of the analgesic paracetamol (acetaminophen). It is normally produced only in small amounts, and then almost imme ...

via the

cytochrome P450 oxidase Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

system, mainly by the subfamily CYP2E1. Hepatic reduced glutathione (GSH) will detoxify this formed NAPQI quickly by if APAP is taken at a proper level. In the case of overdoses, the storage of GSH will not be enough for NAPQI detoxication, thereby resulting in acute liver injury.

Other oxidoreductases

Oxidoreductases In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually uti ...

are enzymes that catalyze the reactions that involve the transfer of electrons.

Methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...

in itself is toxic due to its

central nervous system depression Central nervous system (CNS) depression is a physiological state that can result in a decreased rate of breathing, decreased heart rate, and loss of consciousness possibly leading to coma or death. It is the result of inhibited or suppressed brai ...

properties, but it can be converted to formaldehyde by alcohol dehydrogenase and then converted to formic acid by aldehyde dehydrogenase, which are significantly more toxic.

Formic acid Formic acid (), systematically named methanoic acid, is the simplest carboxylic acid, and has the chemical formula HCOOH and structure . It is an important intermediate in chemical synthesis and occurs naturally, most notably in some ants. Es ...

and

formaldehyde Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...

can cause severe

acidosis Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describes t ...

, damage to the

optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...

, and other life-threatening complications. Methanol conversion

Ethylene glycol Ethylene glycol (IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an odo ...

(common antifreeze) can be converted into toxic

glycolic acid Glycolic acid (or hydroxyacetic acid; chemical formula HOCH2CO2H) is a colorless, odorless and hygroscopic crystalline solid, highly soluble in water. It is used in various skin-care products. Glycolic acid is widespread in nature. A glycolate (so ...

, glyoxylic acid and

oxalic acid Oxalic acid is an organic acid with the systematic name ethanedioic acid and formula . It is the simplest dicarboxylic acid. It is a white crystalline solid that forms a colorless solution in water. Its name comes from the fact that early inve ...

by aldehyde dehydrogenase, lactate dehydrogenase (LDH) and glycolate oxidase in mammalian organisms. The accumulation of the end product of the ethylene glycol mechanism, calcium oxalate, may cause malfunction in the kidney and lead to more severe consequences. Ethylene glycol toxication

Heavy metals

Lead or zinc-based paints and dust are commonly found in old buildings. These dust and paint are dangerous for exposure to children and adults. Their components of lead, zinc, and copper might cause acute diseases. In adults, most of them are affected by occupational exposure, such as welding, painting, or in industries. When a person is exposed to heavy metals for a long period of time, the heavy metals start accumulating in the body, leading to diseases like gastrointestinal and kidney dysfunction, nervous system disorders, skin lesions, vascular damage, immune system dysfunction, birth defects, and cancer.

Other examples

Other examples of toxication by enzymatic metabolism include: * Conversion of secondary amines in the stomach into carcinogenic

nitrosamine In organic chemistry, nitrosamines (or more formally ''N''-Nitrosamines) are organic compounds with the chemical structure , where R is usually an alkyl group. They feature a nitroso group () bonded to a deprotonated amine. Most nitrosamines are ...

s via NO pathway. *

Nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

into the nitrosated carcinogenic

NNK Nicotine-derived nitrosamine ketone (NNK) is one of the key tobacco-specific nitrosamines derived from nicotine. It plays an important role in carcinogenesis. The conversion of nicotine to NNK entails opening of the pyrrolidine ring. Synthesis a ...

(''4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone'') in the lung. * Benzo yrene into the carcinogenic ''benzo yrene diol epoxide'' (BP-7,8-dihydrodiol-9,10-epoxide) * Hypoglycin A into the highly toxic

MCPA MCPA (2-methyl-4-chlorophenoxyacetic acid) is a powerful, selective, widely used phenoxy herbicide. The pure compound is a brown-colored powder. MCPA has been extensively used in agriculture to control broad-leaf weeds as a growth regulator prima ...

- CoA

Toxication by abiotic chemical reactions

Increases in toxicity can also be caused by

chemical reactions. Non-living elements affect the abiotic chemical reactions. Anthropogenic trace compounds (ATCs) have potential toxicity to the organisms in aquatic system.

Arsenic Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, but ...

contamination in drinking water can be chemically toxic. The uptake and metabolism of arsenic may result the damage to body. When organic arsenic is converted into more toxic inorganic arsenic, it causes carcinogenesis, cytotoxicity (toxic to cells) and genotoxicity (causing mutations in genes).{{Cite journal , last1=Shankar , first1=Shiv , last2=Shanker , first2=Uma , last3=Shikha , date=2014-01-01, title=Arsenic contamination of groundwater: a review of sources, prevalence, health risks, and strategies for mitigation , journal=TheScientificWorldJournal , volume=2014 , pages=304524 , doi=10.1155/2014/304524, issn=1537-744X, pmc=4211162, pmid=25374935, doi-access=free

References

Pharmacokinetics Biodegradation