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Toxicity is the degree to which a chemical substance or a particular
mixture In chemistry, a mixture is a material made up of two or more different chemical substances which are not chemically bonded. A mixture is the physical combination of two or more substances in which the identities are retained and are mixed in the ...
of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (
cytotoxicity Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...
) 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 Dose or Dosage may refer to: Music * ''Dose'' (Gov't Mule album), 1998 * ''Dose'' (Latin Playboys album) * ''Dosage'' (album), by the band Collective Soul * "Dose" (song), a 2018 song by Ciara * "Dose", song by Filter from the album '' Short ...
-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 Snake venom is a highly toxic saliva containing zootoxins that facilitates in the immobilization and digestion of prey. This also provides defense against threats. Snake venom is injected by unique fangs during a bite, whereas some species are a ...
there is a dose below which there is no detectable toxic effect. Toxicity is species-specific, making cross-species analysis problematic. Newer
paradigm In science and philosophy, a paradigm () is a distinct set of concepts or thought patterns, including theories, research methods, postulates, and standards for what constitute legitimate contributions to a field. Etymology ''Paradigm'' comes f ...
s and metrics are evolving to bypass animal testing, while maintaining the concept of toxicity endpoints.


Etymology

"Toxic" and similar words derive from Greek τόξον ' (" bow"), a reference to the use of
poisoned arrow Arrow poisons are used to poison arrow heads or darts for the purposes of hunting and warfare. They have been used by indigenous peoples worldwide and are still in use in areas of South America, Africa and Asia. Notable examples are the poisons se ...
s as weapons. This root was chosen because the transliteration of ἰός ', the usual Classical Greek word for "poison", was not distinctive enough from the English word " ion," itself derived from a similar but unrelated Greek root. The literal meaning of the root ''toxo-'' is reflected in such biological names as '' Toxodon'' ("bow-toothed").


Types

There are generally five types of toxic entities; chemical, biological, physical, radiation and behavioural toxicity: * 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 Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...
, 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 Asbestos () is a naturally occurring fibrous silicate mineral. There are six types, all of which are composed of long and thin fibrous crystals, each fibre being composed of many microscopic "fibrils" that can be released into the atmosphere b ...
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 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. * Radiation can have a toxic effect on organisms. * Behavioral toxicity refers to the undesirable effects of essentially therapeutic levels of medication clinically indicated for a given disorder (DiMascio, Soltys, & Shader, 1970). These undesirable effects may include anticholinergic effects, alpha-adrenergic blockade, and dopaminergic effects, among others.


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 . 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. 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 Tobacco smoke is a sooty aerosol produced by the incomplete combustion of tobacco during the smoking of cigarettes and other tobacco products. Temperatures in burning cigarettes range from about 400 °C between puffs to about 900 °C d ...
, and
industrial waste Industrial waste is the waste produced by industrial activity which includes any material that is rendered useless during a manufacturing process such as that of factories, mills, and mining operations. Types of industrial waste include dirt and ...
. 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 endpoints 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.


Classification

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 Tolerable daily intake (TDI) refers to the daily amount of a chemical that has been assessed safe for human being on long-term basis (usually whole lifetime). Originally acceptable daily intake (ADI) was introduced in 1961 to define the daily intake ...
levels).
Pesticide Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampri ...
s provide the example of well-established toxicity class systems and
toxicity label Toxicity labels viz; red label, yellow label, blue label and green label are mandatory labels employed on pesticide containers in India identifying the level of toxicity (that is, the toxicity class) of the contained pesticide. The schemes foll ...
s. 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 The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is an internationally agreed-upon standard managed by the United Nations that was set up to replace the assortment of hazardous material classification and labelli ...
has begun unifying these countries. Global classification looks at three areas: Physical Hazards (explosions and pyrotechnics), Health Hazards and environmental hazards.


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. 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. 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 through a skin patch test analysis, similar to an allergic inflammation patch test. 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 is minor damage (less severe than irritation) within 72 hours of application or for three consecutive days after application. Serious
eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...
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 An allergic response is a hypersensitive immune reaction to a substance that normally is harmless or would not cause an immune response in everyone. An allergic response may cause harmful symptoms such as itching or inflammation or tissue injury. ...
from a dermal application. * Carcinogens induce cancer, or increase the likelihood of cancer occurring. * Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the
central Central is an adjective usually referring to being in the center of some place or (mathematical) object. Central may also refer to: Directions and generalised locations * Central Africa, a region in the centre of Africa continent, also known as ...
and/or peripheral nervous system. It occurs when exposure to a substance – specifically, a
neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
or neurotoxicant– alters the normal activity of the nervous system in such a way as to cause permanent or reversible damage to
nervous tissue Nervous tissue, also called neural tissue, is the main tissue component of the nervous system. The nervous system regulates and controls body functions and activity. It consists of two parts: the central nervous system (CNS) comprising the brain ...
. * 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) The EPA maintains a list of priority pollutants for testing and regulation.


Occupational hazards

Workers in various occupations may be at a greater level of risk for several types of toxicity, including neurotoxicity. The expression "Mad as a hatter" and the "Mad Hatter" of the book
Alice in Wonderland ''Alice's Adventures in Wonderland'' (commonly ''Alice in Wonderland'') is an 1865 English novel by Lewis Carroll. It details the story of a young girl named Alice who falls through a rabbit hole into a fantasy world of anthropomorphic creatur ...
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 for small businesses

=


=Hazards from medical waste and prescription disposal

=


=Hazards in the arts

= 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 In organic chemistry, xylene or xylol (; IUPAC name: dimethylbenzene) are any of three organic compounds with the formula . They are derived from the substitution of two hydrogen atoms with methyl groups in a benzene ring; which hydrogens are sub ...
for cleaning
silk screens Screen printing is a printing technique where a mesh is used to transfer ink (or dye) onto a substrate, except in areas made impermeable to the ink by a blocking stencil. A blade or squeegee is moved across the screen to fill the open mes ...
. 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 The ''Yu-Gi-Oh!'' series features an extensive cast of characters created by Kazuki Takahashi. The series takes place in a fictional city in Japan called Domino City, in which most of the characters that appear in the series originate. Many plot ...
published ''Non-Toxic Intaglio Printmaking'' which detailed twelve innovative Intaglio-type printmaking techniques including
photo etching Photoengraving is a process that uses a light-sensitive photoresist applied to the surface to be engraved to create a mask that protects some areas during a subsequent operation which etches, dissolves, or otherwise removes some or all of the mate ...
, digital imaging,
acrylic Acrylic may refer to: Chemicals and materials * Acrylic acid, the simplest acrylic compound * Acrylate polymer, a group of polymers (plastics) noted for transparency and elasticity * Acrylic resin, a group of related thermoplastic or thermosett ...
-resist hand-etching methods, and introducing a new method of non-toxic lithography.


Mapping environmental hazards

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 Superfund is a United States federal environmental remediation program established by the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA). The program is administered by the United States Environmental Pro ...
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) and PubMed, and from other authoritative sources.


Aquatic toxicity

Aquatic toxicity Aquatic toxicology is the study of the effects of manufactured chemicals and other anthropogenic and natural materials and activities on aquatic organisms at various levels of organization, from subcellular through individual organisms to communi ...
testing subjects key indicator species of fish or
crustacea Crustaceans (Crustacea, ) form a large, diverse arthropod taxon which includes such animals as decapods, seed shrimp, branchiopods, fish lice, krill, remipedes, isopods, barnacles, copepods, amphipods and mantis shrimp. The crustacean gro ...
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. 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.


Alternatives to dose-response framework

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 a screening tool.


See also

*
Agency for Toxic Substances and Disease Registry The Agency for Toxic Substances and Disease Registry (ATSDR) is a federal public health agency within the United States Department of Health and Human Services. The agency focuses on minimizing human health risks associated with exposure to haza ...
(ATSDR) *
Biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...
* Biological warfare * California Proposition 65 (1986) * Carcinogen * Drunkenness *
Indicative limit value In the law of the European Union, indicative limit values, more exactly indicative occupational exposure limit values (IOELVs), are human Acute exposure, exposure limits to hazardous Chemical substance, substances specified by the Council of the Eur ...
*
List of highly toxic gases Many gases have toxic properties, which are often assessed using the LC50 (median lethal dose) measure. In the United States, many of these gases have been assigned an NFPA 704 health rating of 4 (may be fatal) or 3 (may cause serious or perman ...
* Material Safety Data Sheet (MSDS) *
Mutagen In genetics, a mutagen is a physical or chemical agent that permanently changes nucleic acid, genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can ca ...
* Hepatotoxicity * Nephrotoxicity * Neurotoxicity * Ototoxicity *
Paracelsus Paracelsus (; ; 1493 – 24 September 1541), born Theophrastus von Hohenheim (full name Philippus Aureolus Theophrastus Bombastus von Hohenheim), was a Swiss physician, alchemist, lay theologian, and philosopher of the German Renaissance. He w ...
*
Physiologically-based pharmacokinetic modelling Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling technique for predicting the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species. ...
. *
Poison Poison is a chemical substance that has a detrimental effect to life. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figuratively, with a broa ...
* Reference dose *
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 U ...
(RTECS) – toxicity database * Soil contamination * Teratogen * Toxic tort *
Toxication Toxication, toxification or toxicity exaltation is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. The conversion can be caused by enzymatic metabolism in the organisms, as we ...
*
Toxicophore A toxicophore is a chemical structure or a portion of a structure (e.g., a functional group) that is related to the toxic properties of a chemical. Toxicophores can act directly (e.g., dioxins and dioxin-like compounds, dioxins) or can require Drug ...
* Toxin * Toxica, a disambiguation page


References


External links


Agency for Toxic Substances and Disease Registry

Whole Effluent, Aquatic Toxicity Testing FAQ

TOXMAP
Environmental Health e-Maps from the United States National Library of Medicine
Toxseek: meta-search engine in toxicology and environmental health
{{Authority control Pharmacology Toxicology Occupational safety and health