Toxicity

Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism.[1] 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). By extension, the word may be metaphorically used to describe toxic effects on larger and more complex groups, such as the family unit or society at large. 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 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. Considering the limitations of this dose-response concept, a novel Drug Toxicity Index (DTI) has been proposed recently.[2] DTI redefines drug toxicity, identifies hepatotoxic drugs, gives mechanistic insights, predicts clinical outcomes and has potential as a screening tool. 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.[3]

Toxicity
Skull and Crossbones
The skull and crossbones is a common symbol for toxicity.

Types

There are generally four types of toxic entities; chemical, biological, physical and radiation:

  • The R.M.Yassine Scale is the main scale used to measure toxicity.
  • Chemical toxicants include inorganic substances such as, lead, mercury, hydrofluoric acid, and chlorine gas, and organic compounds such as methyl alcohol, most medications, and poisons from living things. While some weakly radioactive substances, such as uranium, are also chemical toxicants, more strongly radioactive materials like radium are not, their harmful effects (radiation poisoning) being caused by the ionizing radiation produced by the substance rather than chemical interactions with the substance itself.
  • Disease-causing microorganisms and parasites are toxic in 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. However, in a host with an intact immune system the inherent toxicity of the organism is balanced by the host's ability to fight back; the effective toxicity is then a combination of both parts of the relationship. In some cases, e.g. cholera, 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 fibers or finely divided silicon dioxide, all of which can ultimately be fatal if inhaled. Corrosive chemicals possess physical toxicity because they destroy tissues, but they're not directly poisonous unless they interfere directly with biological activity. Water can act as a physical toxicant if taken in extremely high doses because the concentration of vital ions decreases dramatically if there's 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.
  • As already mentioned, radiation can have a toxic effect on organisms.[4]

Measuring

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 is often used which relates the probabilities of an outcome for a given individual in a population. One such measure is the LD50. 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 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, 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. Obviously, this approach is very approximate; but such protection factors are deliberately very conservative, and the method has been found to be useful in a deep 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 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 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 end points such as cancer, cardiotoxicity, and skin/eye irritation. Toxicity testing also helps calculate the No Observed Adverse Effect Level (NOAEL) dose and is helpful for clinical studies.[5]

Classification

GHS-pictogram-skull
The international pictogram for toxic chemicals.

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 have 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 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[6][7] has begun unifying these countries.

Global classification looks at three areas: Physical Hazards (explosions and pyrotechnics),[8] Health Hazards[9] and environmental hazards.[10]

Health hazards

The types of toxicities where substances may cause lethality to the entire body, lethality to specific organs, major/minor damage, or cause cancer. These are globally accepted definitions of what toxicity is.[9] Anything falling outside of the definition cannot be classified as that type of toxicant.

Acute toxicity

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 the most exposure to be lethal. The table below shows the upper limits for each category.

Method of administration Category 1 Category 2 Category 3 Category 4 Category 5
Oral: LD50 measured in mg/kg of bodyweight 5 50 300 2 000 5 000
Dermal: LD50 measured in mg/kg of bodyweight 50 200 1 000 2 000 5 000
Gas Inhalation: LC50 measured in ppmV 100 500 2 500 20 000 Undefined
Vapour Inhalation: LC50 measured in mg/L 0.5 2.0 10 20 Undefined
Dust and Mist Inhalation: LC50 measured in mg/L 0.05 0.5 1.0 5.0 Undefined

Note: The undefined values are expected to be roughly equivalent to the category 5 values for oral and dermal administration.

Other methods of exposure and severity

Skin corrosion and irritation are determined though a skin patch test analysis. This examines the severity of the damage done; when it 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 a 14-day period; or causes inflammation which lasts for 14 days in two test subjects. Mild skin irritation 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.

Other categories

  • Respiratory sensitizers cause breathing hypersensitivity when the substance is inhaled.
  • A substance which is a skin sensitizer causes an allergic response from a dermal application.
  • Carcinogens induce cancer, or increase the likelihood of cancer occurring.
  • Reproductively toxic substances cause adverse effects in either sexual function or fertility to either a parent or the offspring.
  • Specific-target organ toxins damage only specific organs.
  • Aspiration hazards are solids or liquids which can cause damage through inhalation.

Environmental hazards

An Environmental hazard can be defined as any condition, process, or state adversely affecting 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.

Common types of environmental hazards

  • Water: detergents, fertilizer, raw sewage, prescription medication, pesticides, herbicides, heavy metals, PCBs
  • Soil: heavy metals, herbicides, pesticides, PCBs
  • Air: particulate matter, carbon monoxide, sulfur dioxide, nitrogen dioxide, asbestos, ground-level ozone, lead (from aircraft fuel, mining, and industrial processes)[11]

The EPA maintains a list of priority pollutants for testing and regulation.[12]

Occupational hazards

The expression "Mad as 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.

Hazards in the arts have been an issue for artists for centuries, even though the toxicity of their tools, methods, and materials 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 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 a new method of non-toxic lithography.[13]

Mapping environmental hazards

There are many environmental health mapping tools. TOXMAP is a Geographic Information System (GIS) from the Division of Specialized Information Services[14] 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 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)[15] and PubMed, and from other authoritative sources.

Aquatic toxicity

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, the EPA currently lists aquatic toxicity as "practically non-toxic" in concentrations greater than 100 ppm.[16]

Exposure Category 1 Category 2 Category 3
Acute ≤ 1.0 mg/L ≤ 10 mg/L ≤ 100 mg/L
Chronic ≤ 1.0 mg/L ≤ 10 mg/L ≤ 100 mg/L

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.

Factors influencing toxicity

Toxicity of a substance can be affected by many different factors, such as the pathway of administration (whether the toxicant is applied to 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 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.

Acute exposure
A single exposure to a toxic substance which may result in severe biological harm or death; acute exposures are usually characterized as lasting no longer than a day.
Chronic exposure
Continuous exposure to a toxicant over an extended period of time, often measured in months or years; it can cause irreversible side effects.

Etymology

"Toxic" and similar words came from Greek τοξον = "bow (weapon)" via "poisoned arrow", which came to be used for "poison" in scientific language, as the usual Classical Greek word ('ιον) for "poison" would transliterate to "io-", which is not distinctive enough. In some biological names, "toxo-" still means "bow", as in Toxodon = "bow-toothed" from the shape.

See also

References

  1. ^ "Definition of TOXICITY".
  2. ^ Dixit, Vaibhav (2019). "A simple model to solve complex drug toxicity problem". Toxicology Research. 8 (2): 157–171. doi:10.1039/C8TX00261D.
  3. ^ "Toxicity Endpoints & Tests". AltTox.org. Retrieved 25 February 2012.
  4. ^ Matsumura Y, Ananthaswamy HN (March 2004). "Toxic effects of ultraviolet radiation on the skin". Toxicology and Applied Pharmacology. 195 (3): 298–308. doi:10.1016/j.taap.2003.08.019. PMID 15020192.
  5. ^ Parasuraman S. Toxicological screening. J Pharmacol Pharmacother [serial online] 2011 [cited 2013 Oct 12];2:74-9. Available from: http://www.jpharmacol.com/text.asp?2011/2/2/74/81895
  6. ^ "About the GHS - Transport - UNECE".
  7. ^ EPA, OCSPP, OPP, US. "Pesticide Labels and GHS: Comparison and Samples".CS1 maint: Multiple names: authors list (link)
  8. ^ "Transport - Transport - UNECE" (PDF).
  9. ^ a b "Transport - Transport - UNECE" (PDF).
  10. ^ "Transport - Transport - UNECE" (PDF).
  11. ^ "Basic Information about Lead Air Pollution." EPA. Environmental Protection Agency, 17 Mar. 2017. Web. Beaubier, Jeff, and Barry D. Nussbaum. "Encyclopedia of Quantitative Risk Analysis and Assessment." Wiley. N.p., 15 Sept. 2008. Web. "Criteria Air Pollutants." EPA. Environmental Protection Agency, 2 Mar. 2017. Web. “USEPA List of Priority Pollutants." The Environmental Science of Drinking Water (2005): 243–45. EPA, 2014. Web "What Are Some Types of Environmental Hazards?" Reference. IAC Publishing, n.d. Web.
  12. ^ https://www.epa.gov/sites/production/files/2015-09/documents/priority-pollutant-list-epa.pdf
  13. ^ Keith Howard; et al. (1988). Non-toxic intaglio printmaking / by Keith Howard ; foreword by Monono Rossol. forward by Monona Rossol; contributions from Elizabeth Dove. Grand Prairie, Alberta: Printmaking Resources. ISBN 978-0-9683541-0-0.
  14. ^ "Reliable information on K-12 science education, chemistry, toxicology, environmental health, HIV/AIDS, disaster/emergency preparedness and response, and outreach to minority and other specific populations".
  15. ^ "TOXNET".
  16. ^ EPA: Ecological risk assessment

External links

Anticholinergic

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. These agents inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, and many other parts of the body. Anticholinergics are divided into three categories in accordance with their specific targets in the central and peripheral nervous system: antimuscarinic agents, ganglionic blockers, and neuromuscular blockers.

Barbiturate overdose

Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe (respiratory depression). Complications of overdose can include noncardiogenic pulmonary edema. If death occurs this is typically due to a lack of breathing.Barbiturate overdose may occur by accident or purposefully in an attempt to cause death. The toxic effects are additive to those of alcohol and benzodiazepines. The lethal dose varies with a person's tolerance and how the drug is taken. The effects of barbiturates occur via the GABA neurotransmitter. Exposure may be verified by testing the urine or blood.Treatment involves supporting a person's breathing and blood pressure. While there is no antidote, activated charcoal may be useful. Multiple doses of charcoal may be required. Hemodialysis may occasionally be considered. Urine alkalinisation has not been found to be useful. While once a common cause of overdose, barbiturates are now a rare cause.

Beta blocker

Beta blockers (beta-blockers, β-blockers, etc.) are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack (myocardial infarction) after a first heart attack (secondary prevention). They are also widely used to treat high blood pressure (hypertension), although they are no longer the first choice for initial treatment of most patients.Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1, β2 and β3 receptors. β1-adrenergic receptors are located mainly in the heart and in the kidneys. β2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. β3-adrenergic receptors are located in fat cells.Beta receptors are found on cells of the heart muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the sympathetic nervous system and lead to stress responses, especially when they are stimulated by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of epinephrine and other stress hormones, and weaken the effects of stress hormones.

In 1964, James Black synthesized the first clinically significant beta blockers—propranolol and pronethalol; it revolutionized the medical management of angina pectoris and is considered by many to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.For the treatment of primary hypertension, meta-analyses of studies which mostly used atenolol have shown that although beta blockers are more effective than placebo in preventing stroke and total cardiovascular events, they are not as effective as diuretics, medications inhibiting the renin–angiotensin system (e.g., ACE inhibitors), or calcium channel blockers.

Calcium channel blocker

Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium (Ca2+) through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate (especially from atrial fibrillation), to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris.

N-type, L-type, and T-type voltage-dependent calcium channels are present in the zona glomerulosa of the human adrenal gland, and CCBs can directly influence the biosynthesis of aldosterone in adrenocortical cells, with consequent impact on the clinical treatment of hypertension with these agents.CCBs have been shown to be slightly more effective than beta blockers at lowering cardiovascular mortality, but they are associated with more side effects. Potential major risks however were mainly found to be associated with short-acting CCBs.

CompTox Chemicals Dashboard

The CompTox Chemicals Dashboard is a freely accessible online database created and maintained by the U.S. Environmental Protection Agency (EPA). The database provides access to multiple types of data including physicochemical properties, environmental fate and transport, exposure, usage, in vivo toxicity, and in vitro bioassay. EPA and other scientists use the data and models contained within the dashboard to help identify chemicals that require further testing and reduce the use of animals in chemical testing. The Dashboard is also used to provide public access to information from EPA Action Plans, e.g. around perfluorinated alkylated substances., Originally titled the Chemistry Dashboard, the first version was released in 2016. The latest release of the database (version 3.0.5) contains manually curated data for over 875,000 chemicals and incorporates the latest data generated from the EPA's Toxicity Forecaster (ToxCast) high-throughput screening program. The Chemicals Dashboard incorporates data from several previous EPA databases into one package including the ToxCast Dashboard, the Endocrine Disruption Screening Program (EDSP) Dashboard and the Chemical and Products Database (CPDat).

Hepatotoxicity

Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease.

The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins) and herbal remedies can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins.

More than 900 drugs have been implicated in causing liver injury (see LiverTox, external link, below) and it is the most common reason for a drug to be withdrawn from the market. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the need for toxicity prediction models (e.g. DTI), and drug screening assays, such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process. Chemicals often cause subclinical injury to the liver, which manifests only as abnormal liver enzyme tests.

Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures.

Hypervitaminosis A

Hypervitaminosis A refers to the toxic effects of ingesting too much preformed vitamin A. Symptoms arise as a result of altered bone metabolism and altered metabolism of other fat-soluble vitamins. Hypervitaminosis A is believed to have occurred in early humans, and the problem has persisted throughout human history.

Toxicity results from ingesting too much preformed vitamin A from foods (such as fish or animal liver), supplements, or prescription medications and can be prevented by ingesting no more than the recommended daily amount.

Diagnosis can be difficult, as serum retinol is not sensitive to toxic levels of vitamin A, but there are effective tests available. Hypervitaminosis A is usually treated by stopping intake of the offending food(s), supplement(s), or medication. Most people make a full recovery.

High intake of provitamin carotenoids (such as beta-carotene) from vegetables and fruits does not cause hypervitaminosis A, as conversion from carotenoids to the active form of vitamin A is regulated by the body to maintain an optimum level of the vitamin. Carotenoids themselves cannot produce toxicity.

Local anesthetic

A local anesthetic (LA) is a medication that causes absence of pain sensation. When it is used on specific nerve pathways (local anesthetic nerve block), paralysis (loss of muscle power) also can be achieved.

Clinical LAs belong to one of two classes: aminoamide and aminoester local anesthetics. Synthetic LAs are structurally related to cocaine. They differ from cocaine mainly in that they have a very low abuse potential and do not produce hypertension or (with few exceptions) vasoconstriction.

They are used in various techniques of local anesthesia such as:

Topical anesthesia (surface)

Topical administration of cream, gel, ointment, liquid, or spray of anaesthetic dissolved in DMSO or other solvents/carriers for deeper absorption

Infiltration

Brachial plexus block

Epidural (extradural) block

Spinal anesthesia (subarachnoid block)

Iontophoresis

Nitrate

Nitrate is a polyatomic ion with the molecular formula NO−3 and a molecular mass of 62.0049 u. Organic compounds that contain the nitrate ester as a functional group (RONO2) are also called nitrates.

Nutmeg

Nutmeg is the seed or ground spice of several species of the genus Myristica. Myristica fragrans (fragrant nutmeg or true nutmeg) is a dark-leaved evergreen tree cultivated for two spices derived from its fruit: nutmeg, from its seed, and mace, from the seed covering. It is also a commercial source of an essential oil and nutmeg butter. The California nutmeg, Torreya californica, has a seed of similar appearance, but is not closely related to Myristica fragans, and is not used as a spice. If consumed in amounts exceeding its typical use as a spice, nutmeg powder may produce allergic reactions, cause contact dermatitis, or have psychoactive effects. Although used in traditional medicine for treating various disorders, nutmeg has no known medicinal value.

Oxygen toxicity

Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen (O2) at increased partial pressures. Severe cases can result in cell damage and death, with effects most often seen in the central nervous system, lungs, and eyes. Historically, the central nervous system condition was called the Paul Bert effect, and the pulmonary condition the Lorrain Smith effect, after the researchers who pioneered the discoveries and descriptions in the late 19th century. Oxygen toxicity is a concern for underwater divers, those on high concentrations of supplemental oxygen (particularly premature babies), and those undergoing hyperbaric oxygen therapy.

The result of breathing increased partial pressures of oxygen is hyperoxia, an excess of oxygen in body tissues. The body is affected in different ways depending on the type of exposure. Central nervous system toxicity is caused by short exposure to high partial pressures of oxygen at greater than atmospheric pressure. Pulmonary and ocular toxicity result from longer exposure to increased oxygen levels at normal pressure. Symptoms may include disorientation, breathing problems, and vision changes such as myopia. Prolonged exposure to above-normal oxygen partial pressures, or shorter exposures to very high partial pressures, can cause oxidative damage to cell membranes, collapse of the alveoli in the lungs, retinal detachment, and seizures. Oxygen toxicity is managed by reducing the exposure to increased oxygen levels. Studies show that, in the long term, a robust recovery from most types of oxygen toxicity is possible.

Protocols for avoidance of the effects of hyperoxia exist in fields where oxygen is breathed at higher-than-normal partial pressures, including underwater diving using compressed breathing gases, hyperbaric medicine, neonatal care and human spaceflight. These protocols have resulted in the increasing rarity of seizures due to oxygen toxicity, with pulmonary and ocular damage being mainly confined to the problems of managing premature infants.

In recent years, oxygen has become available for recreational use in oxygen bars. The US Food and Drug Administration has warned those suffering from problems such as heart or lung disease not to use oxygen bars. Scuba divers use breathing gases containing up to 100% oxygen, and should have specific training in using such gases.

Paracetamol poisoning

Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. This may include feeling tired, abdominal pain, or nausea. This is typically followed by a couple of days without any symptoms after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment some cases will resolve while others will result in death.Paracetamol poisoning can occur accidentally or as an attempt to end one's life. Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other medications. Liver damage results not from paracetamol itself, but from one of its metabolites, N-acetyl-p-benzoquinone imine (NAPQI). NAPQI decreases the liver's glutathione and directly damages cells in the liver. Diagnosis is based on the blood level of paracetamol at specific times after the medication was taken. These values are often plotted on the Rumack-Matthew nomogram to determine level of concern.Treatment may include activated charcoal if the person presents soon after the overdose. Attempting to force the person to vomit is not recommended. If there is a potential for toxicity, the antidote acetylcysteine is recommended. The medication is generally given for at least 24 hours. Psychiatric care may be required following recovery. A liver transplant may be required if damage to the liver becomes severe. The need for transplant is often based on low blood pH, high blood lactate, poor blood clotting, or significant hepatic encephalopathy. With early treatment liver failure is rare. Death occurs in about 0.1% of cases.Paracetamol poisoning was first described in the 1960s. Rates of poisoning vary significantly between regions of the world. In the United States more than 100,000 cases occur a year. In the United Kingdom it is the medication responsible for the greatest number of overdoses. Young children are most commonly affected. In the United States and the United Kingdom paracetamol is the most common cause of acute liver failure.

Poison

In biology, poisons are substances that cause disturbances in organisms, usually by chemical reaction or other activity on the molecular scale, when an organism absorbs a sufficient quantity.The fields of medicine (particularly veterinary) and zoology often distinguish a poison from a toxin, and from a venom. Toxins are poisons produced by organisms in nature, and venoms are toxins injected by a bite or sting (this is exclusive to animals). The difference between venom and other poisons is the delivery method.

Industry, agriculture, and other sectors employ poisonous substances for reasons other than their toxicity. Most poisonous industrial compounds have associated material safety data sheets and are classed as hazardous substances. Hazardous substances are subject to extensive regulation on production, procurement and use in overlapping domains of occupational safety and health, public health, drinking water quality standards, air pollution and environmental protection. Due to the mechanics of molecular diffusion, many poisonous compounds rapidly diffuse into biological tissues, air, water, or soil on a molecular scale. By the principle of entropy, chemical contamination is typically costly or infeasible to reverse, unless specific chelating agents or micro-filtration processes are available. Chelating agents are often broader in scope than the acute target, and therefore their ingestion necessitates careful medical or veterinarian supervision.

Pesticides are one group of substances whose toxicity to various insects and other animals deemed to be pests (e.g., rats and cockroaches) is their prime purpose. Natural pesticides have been used for this purpose for thousands of years (e.g. concentrated table salt is toxic to many slugs). Bioaccumulation of chemically-prepared agricultural insecticides is a matter of concern for the many species, especially birds, which consume insects as a primary food source. Selective toxicity, controlled application, and controlled biodegradation are major challenges in herbicide and pesticide development and in chemical engineering generally, as all lifeforms on earth share an underlying biochemistry; organisms exceptional in their environmental resilience are classified as extremophiles, these for the most part exhibiting radically different susceptibilities.

A poison which enters the food chain—whether of industrial, agricultural, or natural origin—might not be immediately toxic to the first organism that ingests the toxin, but can become further concentrated in predatory organisms further up the food chain, particularly carnivores and omnivores, especially concerning fat soluble poisons which tend to become stored in biological tissue rather than excreted in urine or other water-based effluents.

Apart from food, many poisons readily enter the body through the skin and lungs. Hydrofluoric acid is a notorious contact poison, in addition to its corrosive damage. Naturally occurring sour gas is a notorious, fast-acting atmospheric poison (as released by volcanic activity or drilling rigs). Plant-based contact irritants, such as that possessed by poison ivy or poison oak, are often classed as allergens rather than poisons; the effect of an allergen being not a poison as such, but to turn the body's natural defenses against itself. Poison can also enter the body through faulty medical implants, or by injection (which is the basis of lethal injection in the context of capital punishment).

In 2013, 3.3 million cases of unintentional human poisonings occurred. This resulted in 98,000 deaths worldwide, down from 120,000 deaths in 1990. In modern society, cases of suspicious death elicit the attention of the Coroner's office and forensic investigators.

Of increasing concern since the isolation of natural radium by Marie and Pierre Curie in 1898—and the subsequent advent of nuclear physics and nuclear technologies—are radiological poisons. These are associated with ionizing radiation, a mode of toxicity quite distinct from chemically active poisons. In mammals, chemical poisons are often passed from mother to offspring through the placenta during gestation, or through breast milk during nursing. In contrast, radiological damage can be passed from mother or father to offspring through genetic mutation, which—if not fatal in miscarriage or childhood, or a direct cause of infertility—can then be passed along again to a subsequent generation. Atmospheric radon is a natural radiological poison of increasing impact since humans moved from hunter-gatherer lifestyles though cave dwelling to increasingly enclosed structures able to contain radon in dangerous concentrations. The 2006 poisoning of Alexander Litvinenko was a novel use of radiological assassination, presumably meant to evade the normal investigation of chemical poisons.

Poisons widely dispersed into the environment are known as pollution. These are often of human origin, but pollution can also include unwanted biological processes such as toxic red tide, or acute changes to the natural chemical environment attributed to invasive species, which are toxic or detrimental to the prior ecology (especially if the prior ecology was associated with human economic value or an established industry such as shellfish harvesting).

The scientific disciplines of ecology and environmental resource management study the environmental life cycle of toxic compounds and their complex, diffuse, and highly interrelated effects.

Poison dart frog

Poison dart frog (also known as dart-poison frog, poison frog or formerly known as poison arrow frog) is the common name of a group of frogs in the family Dendrobatidae which are native to tropical Central and South America. These species are diurnal and often have brightly colored bodies. This bright coloration is correlated with the toxicity of the species, making them aposematic. Some species of the family Dendrobatidae exhibit extremely bright coloration along with high toxicity, while others have cryptic coloration with minimal to no amount of observed toxicity. The species that have great toxicity derive this from their diet of ants, mites and termites. Other species however, that exhibit cryptic coloration and low to no amounts of toxicity, eat a much larger variety of prey. Many species of this family are threatened due to human infrastructure encroaching the places they inhabit.

These amphibians are often called "dart frogs" due to the Amerindians' indigenous use of their toxic secretions to poison the tips of blowdarts. However, of over 170 species, only four have been documented as being used for this purpose (curare plants are more commonly used), all of which come from the genus Phyllobates, which is characterized by the relatively large size and high levels of toxicity of its members.

Quinolone antibiotic

A quinolone antibiotic is a member of a large group of broad-spectrum bactericides that share a bicyclic core structure related to the compound 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry.

Nearly all quinolone antibiotics in use are fluoroquinolones, which contain a fluorine atom in their chemical structure and are effective against both Gram-negative and Gram-positive bacteria. One example is ciprofloxacin, one of the most widely used antibiotics worldwide.

Registry of Toxic Effects of Chemical Substances

Registry of Toxic Effects of Chemical Substances (RTECS) is a database of toxicity information compiled from the open scientific literature without reference to the validity or usefulness of the studies reported. Until 2001 it was maintained by US National Institute for Occupational Safety and Health (NIOSH) as a freely available publication. It is now maintained by the private company BIOVIA or from several value-added resellers and is available only for a fee or by subscription.

Serotonin syndrome

Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe. Symptoms include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. Body temperature can increase to greater than 41.1 °C (106.0 °F). Complications may include seizures and extensive muscle breakdown.Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-HTP, St. John's wort, triptans, ecstasy (MDMA), metoclopramide, ondansetron, or cocaine. It occurs in about 15% of SSRI overdoses. It is a predictable consequence of excess serotonin on the central nervous system (CNS). Onset of symptoms is typically within a day of the extra serotonin.Diagnosis is based on a person's symptoms and history of medication use. Other conditions that can produce similar symptoms such as neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic toxicity, heat stroke, and meningitis should be ruled out. No laboratory tests can confirm the diagnosis.Initial treatment consists of discontinuing medications which may be contributing. In those who are agitated, benzodiazepines may be used. If this is not sufficient, a serotonin antagonist such as cyproheptadine may be used. In those with a high body temperature active cooling measures may be needed. The number of cases of serotonin syndrome that occur each year is unclear. With appropriate treatment the risk of death is less than one percent. The high-profile case of Libby Zion, who is generally accepted to have died from serotonin syndrome, resulted in changes to graduate medical education in New York State.

Toxicology testing

Toxicology testing, also known as safety assessment, or toxicity testing, is conducted to determine the degree to which a substance can damage a living or non-living organisms. It is often conducted by researchers using standard test procedures to comply with governing regulations, for example for medicines and pesticides. Much toxicology is considered to be part of the field of preclinical development. Stages of in vitro and in vivo research are conducted to determine safe doses of exposure in humans before a first-in-man study. Toxicology testing may be conducted by the pharmaceutical industry, biotechnology companies or contract research organizations.

Water intoxication

Water intoxication, also known as water poisoning, hyperhydration, overhydration, or water toxemia is a potentially fatal disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside safe limits by excessive water intake.

Under normal circumstances, accidentally consuming too much water is exceptionally rare. Nearly all deaths related to water intoxication in normal individuals have resulted either from water-drinking contests, in which individuals attempt to consume large amounts of water, or from long bouts of exercise during which excessive amounts of fluid were consumed. In addition, water cure, a method of torture in which the victim is forced to consume excessive amounts of water, can cause water intoxication.

Water, just like any other substance, can be considered a poison when over-consumed in a specific period of time. Water intoxication mostly occurs when water is being consumed in a high quantity without adequate electrolyte intake.Excess of body water may also be a result of a medical condition or improper treatment; see "hyponatremia" for some examples. Water is considered one of the least toxic chemical compounds, with an LD50 of over 90 ml/kg in rats.

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