Toxicity is the degree to which a
chemical substance
A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent Chemical element, elements by physical separation m ...
or a particular
mixture of substances can damage an
organism
In biology, an organism () is any life, living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy (biology), taxonomy into groups such as Multicellular o ...
. Toxicity can refer to the effect on a whole organism, such as an
animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
,
bacterium
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were a ...
, or
plant
Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...
, as well as the effect on a substructure of the organism, such as a
cell (
cytotoxicity) or an organ such as the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
(
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cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fr ...
). By extension, the word may be
metaphor
A metaphor is a figure of speech that, for rhetorical effect, directly refers to one thing by mentioning another. It may provide (or obscure) clarity or identify hidden similarities between two different ideas. Metaphors are often compared wit ...
ically used to describe toxic effects on larger and more complex groups, such as the
family
Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Idea ...
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
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 ...
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. Toxicity is species-specific, making cross-species analysis problematic. Newer
paradigms and metrics are evolving to bypass
animal testing
Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...
, while maintaining the concept of toxicity endpoints.
Etymology
"Toxic" and similar words derive from
Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
τόξον ' ("
bow"), a reference to the use of
poisoned arrows 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
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...
s 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
A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and ...
, bacterium or
worm can reproduce to cause a serious
infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable d ...
. However, in a host with an intact
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...
, 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
Coal is a combustible black or brownish-black sedimentary rock, formed as stratum, rock strata called coal seams. Coal is mostly carbon with variable amounts of other Chemical element, elements, chiefly hydrogen, sulfur, oxygen, and nitrogen ...
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 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
Gasoline (; ) or petrol (; ) (see ) is a transparent, petroleum-derived flammable liquid that is used primarily as a fuel in most spark-ignited internal combustion engines (also known as petrol engines). It consists mostly of organic ...
,
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. 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 level The no-observed-adverse-effect level (NOAEL) denotes the level of exposure of an organism, found by experiment or observation, at which there is no biologically or statistically significant increase in the frequency or severity of any adverse effe ...
s,
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 has begun unifying these countries.
Global classification looks at three areas: Physical Hazards (explosions and pyrotechnics), Health Hazards
and
environmental hazard
An environmental hazard is a substance, state or event which has the potential to threaten the surrounding natural environment or adversely affect people's health, including pollution and natural disasters such as storms and earthquakes. It can ...
s.
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
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
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.
* Carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subst ...
s 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 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 matur ...
or neurotoxicant– alters the normal activity of the nervous system in such a way as to cause permanent or reversible damage to nervous tissue.
* Reproductively toxic substances cause adverse effects in either sexual function or fertility
Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Ferti ...
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
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 ...
: detergents, fertilizer, raw sewage, prescription medication, pesticides, herbicides, heavy metals, PCBs
* 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 ...
: 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 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 a ...
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
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
Digital imaging or digital image acquisition is the creation of a digital representation of the visual characteristics of an object, such as a physical scene or the interior structure of an object. The term is often assumed to imply or include ...
, acrylic-resist hand-etching methods, and introducing a new method of non-toxic lithography
Lithography () is a planographic method of printing originally based on the immiscibility of oil and water. The printing is from a stone ( lithographic limestone) or a metal plate with a smooth surface. It was invented in 1796 by the German ...
.
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
The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it ...
'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 Environmental Protection Agen ...
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
PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintain ...
, 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
Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% ...
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.
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 (ATSDR)
* Biological activity
* Biological warfare
Biological warfare, also known as germ warfare, is the use of biological toxins or infectious agents such as bacteria, viruses, insects, and fungi with the intent to kill, harm or incapacitate humans, animals or plants as an act of war. ...
* California Proposition 65 (1986)
* Carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subst ...
* Drunkenness
* Indicative limit value
* List of highly toxic gases
* Material Safety Data Sheet (MSDS)
* Mutagen
* 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 fr ...
* Nephrotoxicity
* Neurotoxicity
* Ototoxicity
* Paracelsus
* Physiologically-based pharmacokinetic modelling.
* Poison
* Reference dose
* Registry of Toxic Effects of Chemical Substances (RTECS) – toxicity database
* Soil contamination
* Teratogen
* Toxic tort
* Toxication
* Toxicophore
* 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